Drug Trend Report

Transcription

Drug Trend Report

2010 DRUG TREND REPORT
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U
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BR40167I
UNION
BUG-FPO
www.medco.com
To our clients and friends:
We are pleased to share Medco’s 2010 Drug Trend Report highlighting 2009 data representing trends across our base
of clients. It’s clear that even as the rancor in Washington over healthcare reform ensued, Medco and our clients were
already planning for what’s next. Inside these pages, you’ll discover insights and solutions to help you prepare for the
challenges ahead.
Specialty trend maintained an upward climb throughout 2009, ending at 14.7%. Inflation in branded drugs accelerated
to an all-time high of 9.2%, while generic drug inflation remained flat at 0.3%. Despite these increases, Medco clients
realized an average drug trend of 3.7%. Notably, Medco clients with more than 50% mail-order pharmacy penetration
experienced virtually no trend increase (0.1% growth), while clients with less than 50% mail-order penetration
experienced a markedly higher trend increase rate of 5.3%.
Among the other insights revealed in this year’s report:
The generic dispensing rate increased 3.4% to 67.5% as Medco clients continued to embrace savings from generic
drugs. Within the next 3 years, a series of blockbuster drugs will become first-time generics.
Many former “adult” diseases are becoming more prevalent in children as obesity rates soar. Manufacturers are
filing patent extensions for pediatric indications to keep pace. Plans must develop disease prevention programs
and adjust benefit strategies to effectively manage chronic and complex conditions in ever-younger populations.
Central nervous system, endocrine and diabetes, and musculoskeletal and rheumatological drugs will account for
almost 50% of drug trend through 2012.
By fostering research partnerships with leading academic and clinical institutions, Medco remains committed to leading
the transition to precision medicine. The acquisition of DNA Direct, Inc., in early 2010 builds on this foundation—and
transforms research into actionable services designed to meet the expectations of our clients and patients.
This year’s report dissects the key factors that accelerated or moderated trend last year and examines the developments
that will shape trend moving forward. It also showcases many of the ways in which leaders are both innovating
and adapting their practices, policies, and programs to keep pace with the momentum of scientific discoveries and
opportunities associated with healthcare reform.
We encourage you to collaborate with your account manager to take advantage of what’s next.
Sincerely,
David B. Snow, Jr.
Chairman and CEO
Robert S. Epstein, M.D., M.S.
Chief Medical Officer, President, Medco Research Institute
P.S. For additional copies of this report, please contact your Medco account representative. A PDF with supplemental
content is available for download at drugtrend.com.
2010 drUG TrENd rEporT
taBlE of coNtENts
ExEcutivE suMMary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2–17
> iNfluENciNg What’s NExt | 2009 tRend In peRspectIve
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2009 drug trend overview. . . . . . .
Unit costs . . . . . . . . . . . . . . . . .
Utilization . . . . . . . . . . . . . . . . .
Drug trend drivers and moderators .
Specialty healthcare . . . . . . . . . . .
Medicare trend . . . . . . . . . . . . . .
Demographics of trend. . . . . . . . .
National trend . . . . . . . . . . . . . .
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> WhErE to focus NExt | THE fOrCES SHAPiNg TrEND
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Trend projections . . . . . . . . . . . . . . . . . . .
Marketplace projections . . . . . . . . . . . . . . .
Cardiovascular agents . . . . . . . . . . . . . . . .
Central nervous system agents . . . . . . . . . .
Endocrine and diabetes agents . . . . . . . . . .
Musculoskeletal and rheumatological agents
Respiratory agents . . . . . . . . . . . . . . . . . .
Oncology agents . . . . . . . . . . . . . . . . . . . .
Other areas of drug development . . . . . . . . .
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> What’s NExt iN hEalthcarE | THE wAY fOrwArD9
•
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What are we facing now? . . . . . . . . . . . . . .
Wired collaborative care for the whole patient
Wiring healthcare for women . . . . . . . . . . .
Leading the way in personalized medicine . . .
What’s next? . . . . . . . . . . . . . . . . . . . . . .
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77
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rEfErENcEs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
indicates more details are available.
to view, click the icon wherever it appears.
INFLUENCING
WHAT’S NEXT
2009 TrENd IN pErSpECTIvE
iNfluENciNg What’s NExt
a look back at 2009 reveals:
> key areas of prescription drug trend
• Diabetes
• Asthma&COPD
• Antivirals
> the events that shaped trend in top areas
• Inflation
• Safetyreviews,updates
• Evergreeninginpediatrics
> highlights in specialty and Medicare
I N F LU E N C I N G W H AT ’S N E XT
2009 drug trend overview
Despite uncertainty surrounding healthcare reform, our continued collaboration with clients helped them shape
benefit design, coverage selection, and benefit use throughout 2009.
In this section, we recap the top trends that shaped healthcare 2009. Here we review the numbers and news that provided
the context for what’s next.
Drug trend, or the percent change in plan spending from one year to the next,* increased to 3.7%. Excluding specialty
medications, 2009 trend rose to 1.8%. Utilization grew 1.3%, a marked increased from the -1.1% reported in 2008, and
unit cost rose 2.4%. Inflation for branded drugs was 9.2%—almost a full percentage point higher than reported in 2008.
Diabetes, respiratory, and oral antiviral categories contributed the largest percentage to trend and each had > 11% trend.
Medco clients continued to implement benefit strategies that contain costs: The average generic dispensing rate for
the entire Medco client base was 67.5%, up from 64.1% reported last year. Over the next 2 to 3 years, many blockbuster
branded drugs will become available as generic drugs. Plans will have substantial savings opportunities as these lowcost alternatives become available. Mail-order penetration rate was 34.2%.† Clients with > 50% mail-order penetration
experienced slight trend growth, while clients with < 50% mail-order penetration experienced meaningfully higher
growth (0.1% versus 5.3%, respectively).
Specialty trend continued a double-digit growth rate, ending 2009 at 14.7%. Specialty pharmacy growth is expected
to continue climbing as more products are approved. Areas to watch include oncology, rheumatoid arthritis, multiple
sclerosis, and lupus. The different compositions of drug specialty lists between competitors can make trend comparisons
challenging. However, when adjusting for the size and composition of different specialty drug lists across our competitors,
our specialty drug trend is one of the lowest in the industry.
* reported trends are based on 2 years’ data on pharmaceutical spending. Drug trend percent includes 201 clients representing approximately 65% of consolidated drug spending.
The sample comprises clients who offer integrated (mail-order and retail) pharmacy benefit options for members. Clients with membership enrollment changes > 50% were
excluded from the analysis. Plan spending is reported on a per-eligible per-month (PEPM) basis, unless otherwise specified. An “eligible” is a household, which may include
multiple members who are covered under the same plan. Plan spending comprises the net cost to plan sponsors less discounts, rebates, subsidies, and member cost share.
†
generic dispensing rates and mail-order penetration rates represent the total consolidated Medco client base.
click to view more details.
3
Total Medicare drug trend was 1.7%. The analysis of Medicare trend is based on 2 years’ data of pharmaceutical spending
by enrollees in Medicare Part D (PDP, MA-PD) and employer-primary coverage plans (retiree drug subsidy plans [RDS]).
Medicare Part D trend was 5.2% while employer-primary coverage plan trend was 0.3%.
> trENd coMpoNENts
Our 2009 analysis revealed a 3.7% prescription drug trend from January 1, 2009, to December 31, 2009. This figure represents
a slight increase over the 3.3% trend reported for 2008. Drug trend for 2009 without specialty was 1.8%. Unit cost and
utilization comprise drug trend.
Unit costs are the plan sponsor’s cost per unit of therapy. Unit costs vary if:
• Drugs prices increase (inflation) or
• Users move to different drug options within a class, or across classes (shift in therapy mix)
Unit costs are expressed as per eligible per month (PEPM) within the context of overall trend and include cost per unit of
therapy. However, within discussions of specific chapter and category contributions to trend, unit costs are expressed as cost
per day of therapy and are expressed as per member per month (PMPM).
Utilization refers to the quantity of drugs obtained by plan members. Utilization varies if:
• More members start taking drugs (increase in number of users or treatment rate), or
• Members are more (or less) adherent to their drug therapy (change in number of days, or treatment intensity)
Unless specified otherwise, utilization is expressed in terms of days of therapy per eligible.
Unit costs grew 2.4% and, fueled by brand inflation, remained historically high. Utilization rebounded from the negative
growth reported in 2008 to 1.3%, but remained consistently low. Figure 1 reviews percentage growth in annual drug trend,
utilization, and unit cost since 2006.
figurE 1.
year over year trend increased slightly; utilization rebounded
TrENd, UTILIZATIoN, ANd UNIT CoSTS 2006 To prESENT
Trend
5
change (%) year to year
1.8
2.0
2.4
1.6
1.3
1.0
0.4
-1
Source: Medco data
d r u g tr e n d r e po rt
2.8
0
-2
4
3.7
3.3
2
1
Unit cost
4.4
4
3
Utilization
>
2010
-1.1
2006
2007
2008
2009
unit costs
Brand inflation, partially offset by big-name generic conversions, contributed to net unit cost growth. 2009 marked the
generic availability of many billion-dollar drugs. Table 1 shows a list of 2009 first-time generic approvals. Notably, firsttime generics, Imitrex® tablets and injection, Topamax®, Adderall XR®, Prevacid®, and Valtrex® totaled over $9 billion in U.S.
market sales for 2008, according to IMS Health.
First-time generics can reduce costs within therapeutic categories, especially if they launch early in the year. Generic
conversions for migraine and seizure medications occurred early in the year and contributed to the decline in costs per
day of therapy within the respective categories: -6.1% and -20.7%. Pulmicort Respules® became available as a generic late
in the year and although net cost PEPM increased over 600% for the generic formulation (budesonide), the net PEPM
cost remained approximately 50% less than the brand. Net plan cost PEPM decelerated 15.1% and PEPM utilization (days)
dropped 28.4%, a trend that is expected to continue with shifts in mix from the brand to the generic.
TABLE 1.
first-time generic approvals with prior-year u.s. sales >$125 million1,2
generic
approval
Brand name and
dosage form
generic name
uses
1Q 2009
Depakote® ER
divalproex extended-release
tablets
sumatriptan injection
and tablets
topiramate tablets
Seizures, bipolar disorder,
migraine
Migraine
mixed salts of a single-entity
amphetamine product
capsules
mycophenolate mofetil
capsules and tablets
Attention deficit
hyperactivity disorder
(ADHD)
Organ rejection
bicalutamide tablets
tacrolimus
clindamycin/benzoyl
peroxide gel
clonidine transdermal system
Prostate cancer
Organ rejection
Acne
fexofenadine 60 mg/
pseudoephedrine 120 mg
extended-release tablets
lansoprazole delayed-release
capsules
tramadol extended-release
tablet
valacyclovir tablets
budesonide inhalation
suspension
Allergies
Imitrex®
Topamax®
2Q 2009
Adderall XR®
CellCept®
3Q 2009
Casodex®
Prograf®
BenzaClin®
Catapres-TTS®
4Q 2009
Allegra-D® 12 Hour
Prevacid®
Ultram® ER
Valtrex®
Pulmicort Respules®
Seizures, migraines
Market sales in
2008 ($MM)
$736
injection: $205
Tablets: $1,043
$2,400
$1,600
$777
$228
$642
$264
High blood pressure
$212
$465
(all strengths)
gastroesophageal reflux
disease (gErD), ulcers
Moderate to severe chronic
pain
Herpes infections
Asthma
$2,948
$206
$2,020
$876
Sources: u.S. food and Drug Administration (fDA) 1; iMS Health (retail sales)2
fDA approval of a first-time generic may not align with market availability. for a complete list of first-time generic approvals, consult the u.S. fDA website.1
5
News behind the numbers
New this year, the Drug Trend Report highlights significant events that may have directly or indirectly influenced the
industry or marketplace in 2009.
• Mylan received final FDA approval for divalproex ER 250 mg and 500 mg in January 2009. Wockhardt also received final
FDA approval for the 250-mg strength.
• Dr. Reddy’s launched an authorized generic for Imitrex tablets in November 2008, and Par launched an authorized
generic for Imitrex injection in the same month. On February 6, 2009, several companies received final approval for
generic sumatriptan injection. On February 9, 2009, Teva received final FDA approval for their generic sumatriptan
25-mg, 50-mg, and 100-mg tablets. Teva was granted shared 180-day exclusivity. On the same day, Ranbaxy also
received final FDA approval for their generic sumatriptan 100-mg tablets with shared 180-day exclusivity.
• Teva launched their authorized generic for Shire’s Adderall XR (mixed salts of a single-entity amphetamine product)
5-mg, 10-mg, 15-mg, 20-mg, 25-mg, and 30-mg capsules. The launch is the result of patent litigation settlement
between Shire and Teva’s subsidiary, Barr, announced in August 2006. Under the terms of the agreement, Teva has 180
days of exclusivity from the date of commercial launch. Shire and Impax have also reached a settlement agreement
allowing Impax to market an authorized generic version of Adderall XR 181 days following Teva/Barr’s launch.
• May marked the launch of Apotex’s generic for Roche’s CellCept® (mycophenolate mofetil tablets, 500 mg, and
mycophenolate mofetil capsules, 250 mg) and generic formulations from five additional manufacturers.
• A generic for Prograf® was approved August 10, 2009, but was not launched/available until October 13, 2009.
• Ranbaxy’s Valtrex (valacyclovir) generic received approval in January 2007, but did not launch until 2009.
• The 2008 settlement agreement between AstraZeneca and Teva allowed Teva to commence sales of budesonide
inhalation suspension, under an exclusive license from AstraZeneca beginning December 15, 2009.
> Enhancing the generic opportunity
In 2009, upcoming patent expirations may have contributed to inflation for some brands (see details within the “Drug
trend drivers and moderators” section). In many cases, net plan costs also increased for a generic formulation for which
market exclusivity had been granted, albeit not as much as increases seen for the respective brands with upcoming patent
expirations. However, shifts in therapy mix, even to an exclusive generic, may offer substantial savings to a plan. First-time
generics enable lower costs via use as:
• A substitution for the higher-cost brand-name drug (or generic equivalent) and/or
• An alternative to brands in the class (a generic alternative)
In recent years, 6-month exclusivity in generic marketing (which keeps generic prices temporarily high) has tempered the
rate at which plan sponsors realize the full savings potential of shifts in therapy mix. However, even with the prevalence of
exclusivity and shared exclusivity, generic drugs still present significant savings opportunities.
> Inflation
The generic opportunity swell that began in mid 2006 will likely grow in the next few years. Notable impending patent
expirations (subject to patent litigation) and their respective 2008 sales include2:
6
2010
Flomax® $1.3B
Zyprexa® $1.8B
Effexor XR® $2.8B
Lipitor® $6.3B
Aricept® $1.2B
Cozaar®/Hyzaar® $1.3B
> 2010
2011
2012
Actos® $2.6B
Lexapro® $2.5B
Seroquel® $3.2B
Plavix® $3.9B
Singulair® $3.2B
Congressional leaders, through the U.S. Government Accountability Office (GAO) launched an investigation into prescription
drug price increases. In late 2009, the GAO concluded its investigation and published the report.3 The report confirmed that
the number of prescription drugs with “extraordinary” price increases, or single price-point increases > 100%, has steadily
climbed in the last few years.
Figure 2 depicts inflation in branded and generic drugs within the Medco book of business mapped onto the number of
drug products with extraordinary price increases within the same years. The report distinguishes between drug brands,
including all dosage forms, and brand-name drug products, where each drug dosage is considered separately.3 In the latter
case, there were 47 brand-name drug products in 2006, 74 in 2007, and 71 in 2008 that had extraordinary price increases. The
frequencies are reported using NDC-9s.3 The GAO report designates which increases were attributable to the manufacturer
and which increases resulted from repackaging and distribution. Medco does not purchase repackaged products for its
mail-service pharmacies.
Generic drug inflation remained consistently low at 0.3%. The Consumer Price Index, All Items, Urban (CPI-U) measures
inflation as consumers experience it in their day-to-day lives and is projected onto Average Wholesale Price (AWP) inflation
(Figure 2). 2009 year-end CPI-U dipped to -0.4% from 3.8% at the close of 2008.4 Prescription drug inflation continues to
outpace overall CPI-U and contributes greatly to increases in unit costs. See “News behind the numbers” sections following
each trend driver therapeutic category.
figurE 2.
inflation continued upward climb
prESCrIpTIoN drUG INFLATIoN IN brANd ANd GENErIC drUGS ANd CpI-U
Brand
10
inflation (%)
CPI-U
9.2
9
7
Total
Generic
Number of brand-name drug products that had extraordinary price increases
8.3
6.7
6.3
5.2
5
7.4
6.9
5.5
5.3
4.9
4.9
4.7
3
1
-1
0.3
0.5
0.3
2006
2007
2008
2009
47
74
71
N/A
0.5
0.4
0.2
2004
2005
51
39
Sources: Medco data; u.S. government Accountability Office3; u.S. Bureau of Labor Statistics4
CPi-u = Consumer Price index, All items, urban.
7
2 0 0 9 t r en d in p e r s p ecti v e
Utilization
Utilization grew in contrast to the decline reported last year. However, unit costs contributed a greater proportion to overall
trend. Utilization growth occurs because more new users take a drug (treatment rate), or because current users take more
of the drug (treatment intensity).
• Treatment rate measures the number of people who use a drug to treat a specific disease.
• Treatment intensity measures the average number of treatment days per year per user.
> The Rise of REMS
Safety concerns surrounded many therapeutic categories identified as trend drivers and may have tempered utilization
in 2009. The FDA issued more early communications about ongoing safety reviews, follow-up communications, public
health advisories, and information for healthcare professional sheets than ever before. In early 2010, the FDA revised the
communications format to include only Drug Safety Communications that will replace all previous issuances.
Under the Food and Drug Administration Amendments Act of 2007, the FDA was granted authority to require that drug
manufacturers submit risk evaluation and mitigation strategies (REMS)5 to ensure that the benefits of a medication
outweigh any associated risks. At the end of 2009, 98 drugs had approved REMS.
Risk Evaluation and Mitigation Strategies (REMS)
In 2009, the FDA required more REMS submissions than any previous year. The Food and Drug Administration
Amendments Act of 2007 (FDAAA) granted the FDA the authority to require submission and implementation of
a REMS if the FDA determines a REMS is necessary to ensure that a drug’s benefits outweigh its risks.
The REMS program represents an evolution of the previous RiskMAP requirements granted for some drugs
before FDAAA. REMS components can include medication guides, patient package inserts, a communication plan
for healthcare providers, and other elements to ensure safe use for patients, prescribers, and providers.
Draft guidance for the industry titled Format and Content of Proposed Risk Evaluation and Mitigation Strategies
(REMS), REMS Assessments, and Proposed REMS Modifications5 details the format for submission, describes each
REMS component, provides examples of the components, and lists FDA contacts for REMS.
The draft guidance suggests that REMS may have several of the following requirements depending on the level
of risk as deemed by the FDA. REMS may require:
• Special training (e.g., experience, certification) by healthcare providers who prescribe or dispense the drug
• That the drug can only be dispensed to patients in certain settings (e.g., hospitals)
• That the drug can only be dispensed following evidence of safe-use conditions (e.g., appropriate lab test results)
• Patient monitoring/patient registry enrollment
The FDA approved 19 new molecular entities (NMEs), nine biologics, and five therapeutic biologics in 2009. REMS
requirements accompanied 10 of these new drugs. Table 2 displays new drugs and biologics approved by the FDA in 2009.
Table 3 shows the new indications approved by the FDA in 2009.
8
>
2010
TABLE 2.
New drug and biologic approvals in 20096,7
Brand name
generic name
type
uses
1Q 2009
Savella®*
riaSTAP®*
Agriflu®
milnacipran
fibrinogen concentrate
influenza virus vaccine
NME
B
B
ATryn®*
Uloric®
Afinitor®*
Ixiaro®
antithrombin alfa, recombinant
febuxostat
everolimus
Japanese encephalitis vaccine,
inactivated
B
NME
NME
B
fibromyalgia
Congenital fibrinogen deficiency
immunization against subtypes
A and B influenza virus
Hereditary antithrombin deficiency
gout
renal cell carcinoma
immunization against Japanese
encephalitis virus
Coartem®*
Ulesfia™
Simponi™*
artemether/lumefantrine
benzyl alcohol lotion
golimumab
NME
NME
TB
Dysport®*
Fanapt™
Samsca®*
abobutulinumtoxinA
iloperidone
tolvaptan
TB
NME
NME
Besivance™
Ilaris®*
besifloxacin topical suspension
canakinumab
NME
TB
Multaq®*
Effient®*
dronedarone
prasugrel
NME
NME
Onglyza®
Livalo®
Saphris®
Hiberix®
saxagliptin
pitavastatina
asenapine
Haemophilus b conjugate vaccine
NME
NME
NME
B
Sabril®*
Bepreve®
Vibativ®
vigabatrin
bepotastine ophthalmic solution
telavancin
NME
NME
NME
gammaplex®
Folotyn®*
Stelara™*
immune globulin intravenous, human
pralatrexate
ustekinumab
B
NME
TB
Berinert®*
Cervarix®
C1 esterase inhibitor, human
human papillomavirus bivalent
(types 16 and 18) vaccine,
recombinant
pazopanib
ofatumumab
romidepsin
ecallantide
von willebrand factor/coagulation
factor Viii complex, human
B
B
2Q 2009
3Q 2009
4Q 2009
Votrient®*
Arzerra®*
Istodax®
Kalbitor®†
Wilate®
NME
TB
NME
TB
B
Quarter
Acute, uncomplicated malaria
Head lice
rheumatoid arthritis, psoriatic arthritis,
and ankylosing spondylitis
Cervical dystonia, wrinkles
Schizophrenia
Hypervolemic and euvolemic
hyponatremia
Bacterial conjunctivis
Cryopyrin-associated periodic
syndromes (CAPS)
Atrial fibrillation, atrial flutter
reduction of thrombotic
cardiovascular events
Type 2 diabetes
Hyperlipidemia
Schizophrenia, bipolar i disorder
immunization against Haemophilus
influenzae type B
infantile spasms,* complex partial sezures
Allergic conjunctivits
Complicated skin and skin structure
infections due to susceptible
gram-positive bacteria
Primary humoral immunodeficiency
Peripheral T-cell lymphoma
Plaque psoriasis
Acute attacks of hereditary angioedema
Prevention of cervical cancer, cervical
intraepithelial neoplasia, and
adenocarcinoma in situ
Advanced renal cell carcinoma
Chronic lymphocytic leukemia
Cutaneous T-cell lymphoma
Acute attacks of hereditary angioedema
von willebrand disease
Sources: “The Pink Sheet”6 and u.S. food and Drug Administration7
The table shows new prescription drugs approved by the fDA during 2009. This list does not include NME diagnostic agents. Three types of new drugs are shown: NME = New
molecular entity; TB = Therapeutic biologic (approved by the Center for Drug Evaluation and research); B = Biologic (approved by the Center for Biologics Evaluation and research).
Bold text indicates specialty drugs.
* Approved rEMS
† Priority review
a
Livalo received fDA approval, but a launch date has not been announced.
9
TABLE 3.
New indications approved in 20098,9
Quarter
Brand nameGeneric nameUses
1Q 2009
Zingo™
lidocaine powder
Local analgesia prior to venipuncture in adults
Copaxone®
glatiramer injection
Treatment of multiple sclerosis after first
clinical episode
Symbicort®
budesonide/formoterol inhalation
Treatment of chronic obstructive pulmonary disease
Humatrope®
somatropin injection
Treatment of short stature in pediatric patients small
for gestational age
Reclast®
zoledronic acid injection
Treatment and prevention of glucocorticoid-induced
osteoporosis
Symbyax®
fluoxetine/olanzapine
Acute treatment of treatment-resistant depression
Lexapro®
escitalopram
Treatment of adolescent major depressive disorder
2Q 2009
Axert®
almotriptan
Acute treatment of pediatric migraine
Cycloset®
bromocriptine
Treatment of type 2 diabetes as adjunctive therapy
with sulfonylureas
Avastin®
bevacizumab injection
Treatment of glioblastoma
Azor®
amlodipine/olmesartan
First-line therapy for hypertension
Risperdal Consta® risperidone long-acting injection
Maintenance treatment of bipolar I disorder
Cimzia®
certolizumab injection
Treatment of adults with moderately to severely
active rheumatoid arthritis
Adcirca®
tadalafil
Treatment of pulmonary arterial hypertension
Reclast®
zoledronic acid injection
Prevention of osteoporosis in
postmenopausal women
3Q 2009 Alimta®
pemetrexed
Maintenance therapy for locally advanced or
metastatic non-small cell lung cancer
Isentress®
raltegravir
Treatment-naïve patients with HIV
Plan B®
levonorgestrel
OTC availability changed to age 17 and older
Tekturna HCT™
aliskiren/HCTZ
First-line treatment of hypertension
Forteo®
teriparatide injection
Treatment of osteoporosis associated with
glucocorticoid therapy and who are at high
risk for fracture
Colcrys®
colchicine
Treatment of acute flairs in adults with gout and
for familial Mediterranean fever
Invega Sustenna™ paliperidone long-acting injection
Once-monthly treatment of schizophrenia
Avastin®
bevacizumab injection
First-line treatment of metastatic renal cell carcinoma
Tracleer®
bosentan
Treatment of pulmonary arterial hypertension
(WHO Group I) in patients with WHO
Class II to IV symptoms
Embeda®
extended-release morphine/ Management of moderate to severe pain
naltrexone requiring continuous analgesia
Intuniv™
guanfacine extended-release
Treatment of attention deficit hyperactivity
disorder (ADHD)
Zirgan™
ganciclovir ophthalmic gel
Treatment of herpes simplex keratitis
4Q 2009
Mirena®
levonorgestrel-releasing
Treatment of heavy menstrual bleeding for women
intrauterine device who choose to use intrauterine contraception
WelChol®
colesevelam oral suspension Reduction of elevated LDL-C in boys and postmenarchal
girls aged 10 to 17 with heterozygous familial
hypercholesterolemia (HeFH)
Crestor®
rosuvastatin
Treatment of pediatric patients aged 10 to 17 with
heterozygous familial hypercholesterolemia
Micardis®
telmisartan
Reduction of the risk of myocardial infarction, stroke,
or death from cardiovascular causes in patients
55 years of age or older
Atacand®
candesartan
Treatment of hypertension in children aged 1 to 17
10
>
2010
TABLE 3.
New indications approved in 20098,9 (cont’d.)
Brand name
generic name
uses
4Q 2009
(cont’d.)
Gardasil®
Byetta®
Lysteda™
Qutenza®
Protonix®
human papillomavirus quadrivalent
(types 6, 11, 16, and 18) vaccine
exenatide injection
tranexamic acid modified-release
capsaicin patch
pantoprazole
Cymbalta®
duloxetine
Abilify®
aripiprazole
Geodon®
Seroquel®
ziprasidone
quetiapine
Seroquel XR®
quetiapine extended-release
Zyprexa®
olanzapine
Prevention of genital warts caused by HPV types 6
and 11 in boys and men aged 9 to 26
Monotherapy treatment for type 2 diabetes
Treatment of cyclic heavy menstrual bleeding
Management of pain due to postherpetic neuralgia
Treatment of erosive esophagitis in pediatric patients
5 years and older
Maintenance treatment of generalized anxiety
disorder in adults
Treatment of irritability associated with autistic
disorder in pediatric patients aged 6 to 17
Maintenance treatment of bipolar I disorder in adults
Treatment of schizophrenia in adolescents aged 13 to 17
and acute manic episodes associated with bipolar I
disorder in children and adolescents aged 10 to 17
Adjunctive treatment in adults with major
depressive disorder
Treatment of schizophrenia and acute mania associated
with bipolar I disorder in adolescents aged 13 to 17
Quarter
Sources: u.S. food and Drug Administration8,9
Consult product label for the exact wording of the indications for these products.
drug trend drivers and moderators
Each year the Drug Trend Report profiles the top therapeutic chapters and categories contributing to drug trend. As in
previous years, categories are examined in depth to allow readers higher resolution and greater insight into what drugs
may be driving trend and costs. This year, the report also examines chapter data in terms of contribution to trend and
net plan costs.
• Therapeutic chapters: 16 designations that correspond to the chapters within the Medco 2009 Formulary Reference
Guide (e.g., cardiovascular)
• Therapeutic categories: more narrow groupings within the chapters identified by diseases they commonly treat
(e.g., antihypertensive)
• Therapeutic class: types of medications within a single category that have similar mechanisms of action (e.g.,
beta-blockers)
> forMulary chaptEr costs aNd trENd drivErs
Over half of every dollar a plan spends on drugs per eligible per month (PEPM) goes toward a central nervous system
(CNS), cardiovascular, or endocrine and diabetes medication. Plan spending is the net cost to plan sponsors after discounts,
rebates, subsidies, and member cost shares have been applied. CNS medications accounted for almost one-quarter (22.8%)
of plan spending. Spending on cardiovascular medications contributed another 20.4%, and endocrine and diabetes
medications contributed an additional 9.4% to net plan costs. Figure 3 highlights the percent contribution to net plan
costs made by each therapeutic chapter in 2009.
11
Figure 4 shows the 10 chapters that contributed the most
to trend in 2009, their associated trend, and growth in
utilization and plan costs per day of therapy. 2008 percent
contribution to trend for these same chapters is also shown.
figure 3. Therapeutic chapters by percent contribution
to plan costs
Obstetrics & gynecology
2.1%
Other
Dermatological
2.6%
2.8%
Urological
2.8%
Biotechnology
3.7%
Antineoplastic &
immunosuppressant
4.3%
Although contributing a slightly lower percent of spending
in 2009 versus 2008, the endocrine and diabetes therapeutic
chapter showed the greatest percent contribution to trend
in 2009. The contributions of respiratory and cardiovascular
chapters increased dramatically from negative doubledigit contributions in 2008, to the third- and fifth-greatest
percent contributors to trend in 2009.
CNS
22.8%
Musculoskeletal &
rheumatological
5.3%
Anti-infective
7.1%
The conversion of Zyrtec® from prescription to overthe-counter status in 2008 set a low benchmark for the
subsequent year-over-year comparison and resulted in the
seemingly large increase in respiratory trend reported this
year. While the CNS category contribution to trend was
almost 50% in 2008, the category percent contribution to
trend barely exceeded 10% in 2009. This decrease resulted
from several high-volume seizure medications becoming
available as generics in both 2008 and 2009. Price increases
in the period prior to patent expiration may have increased
contribution to trend for drugs in these categories.
figure 4. CNS and cardiovascular chapters
contributed most to plan costs
Respiratory
8.3%
Cardiovascular
20.4%
Gastroenterology
8.6%
Endocrine
& diabetes
9.4%
Source: Medco data
Chapter designations are based on Medco 2009 Formulary Reference Guide therapeutic
chapters. CNS = autonomic and CNS drugs, neurology and psychotherapeutic;
cardiovascular = cardiovascular, hypertension, and lipid medications; respiratory =
respiratory, allergy, cough and cold; other = chapters that contributed < 2.0% in 2009:
ophthalmological, 1.4%; diagnostic and miscellaneous, 0.6%; ear, nose, and throat,
0.3%; vitamins, hematinics, and electrolytes, 0.3%. Biotechnology = immunology,
vaccines, and biotechnology. Percentages are rounded and may not add up to 100%.
Endocrine and diabetes chapter contributed most to trend
Top 10 therapeutic chapters ranked by trend contribution
Trend
Utilization
Cost per day
20
15.7
14.4
15
10
12.3
10.7
10.4
8.7
8.9
6.5
6.8
7.1
5
1.9
9.4
8.1
2.2
2.1
2.9
0
3.0
4.3
1.8
0.7 1.1
3.8
2.9
0.8
-0.8
-1.2
-3.4
-5
-4.7
Endocrine
& diabetes
Anti-infective
Respiratory
CNS
Urological
Cardiovascular
Biotechnology
Antineoplastic &
immunosuppresant
Musculoskeletal &
rheumatological
Dermatological
Contribution
to trend (%)
19.7
12.5
11.3
10.1
8.2
7.9
7.6
6.1
4.8
3.8
2008 (%)
22.8
8.4
-20.6
47.5
10.2
-10.4
8.3
12.8
7.6
4.9
Source: Medco data
Spending growth factors multiply to yield total trend, so utilization growth and cost per day of therapy may not be additive.
12
6.8
6.3
> 2010
> thErapEutic catEgoriEs that drovE costs aNd trENd
This section examines trend and cost data for the top therapeutic categories largely responsible for trend growth so
decision makers can isolate individual disease states and drugs driving plan costs. Plan costs are reported as percentage
of total spending and reflect the 2009 net costs to plan sponsors after deductions for discounts, rebates, subsidies, and
member cost share.
Figure 5 shows the 10 therapeutic categories that had the largest percent contributions to trend in 2009, with their
respective year-over-year trend, utilization, and costs per day of therapy. The figure also lists 2008 percent contributions to
trend by these same categories. From 2008 to 2009, the therapeutic categories driving drug trend changed very little in
aggregate with two exceptions: the reemergence of stimulant drugs used to treat attention deficit hyperactivity disorder
(ADHD) and the debut of biotechnology drugs. These two categories replaced seizure control medications and antipsychotic
medications (see “Trend Moderators” section for elaboration). The ADHD category returned to the top 10 after a 4-year
absence. Notably, the percent contribution to trend reported for 2009 is two times larger than the eighth-place figure
(4.8%) reported in 2006 for that category, owing to increased costs and utilization growth. Specialty and nonspecialty
biotechnology drugs will continue driving trend in the near future, given the large number of drugs in the pipeline.
figurE 5.
diabetes, respiratory, and antiviral categories drove trend
Top 10 THErApEUTIC CATEGorIES rANkEd by TrENd CoNTrIbUTIoN
Trend
25
Cost per day
23.8
20.1
20
17.1
15.7
15
10
Utilization
11.4
11.1
8.9
8.7
15.7
13.9
13.5
12.3
12.0
9.1
9.0
14.4
10.9
10.4
10.4
7.1
6.1
5
2.6
3.0
2.3
2.3
Diabetes
Respiratory
Antiviral
ADHD
Selected
neurological
Rheumatological
Urological
Contribution
to trend (%)
16.7
13.8
10.9
10.0
9.9
9.8
2008 (%)
16.7
9.8
13.8
8.6
10.4
14.7
1.7
6.3
0.5
0.7
Biotechnology
Anticoagulant
& antiplatelet
Cancer
& transplant
8.2
7.6
6.4
6.1
10.2
8.3
10.2
12.8
0
-3.4
-5
Source: Medco data
Spending growth factors multiply to yield total trend, so utilization growth and cost per day may not be additive. respiratory = asthma and COPD. Selected neurological = treatments
for Parkinson’s and Alzheimer’s diseases.
13
> top trENd drivErs
1. dIAbETES THErApy
• Contribution to trend: 16.7%
• Trend: 11.1%
• Utilization ∆: 2.3%
• Cost per day of therapy ∆: 8.7%
• Contribution to net plan cost: 7.7%
This category includes medications and equipment used by patients with types 1 and 2 diabetes (Medco 2009 Formulary
Reference Guide [Formulary Guide] Chapter 7.5), predominantly insulin products, noninsulin hypoglycemic drugs, glucose
elevating agents, and medical devices/supplies required to monitor blood glucose levels and administer insulin.
For the past 3 years, the diabetes therapeutic category has contributed the largest percentage to trend. In 2008, trend
contribution was 16.7%. In 2009, the treatment rate decreased; that is, fewer patients filed claims for diabetes medications
(-1.2% relative change). However, the number of days per patient increased by just under 4.0%, suggesting that more
prescriptions were filled per patient.
Diabetes medication utilization grew in patients aged < 19 by 5.3%, the largest increase across age group quintiles analyzed.
Net plan costs for diabetes medications were highest in patients aged 50 to 64 (9.7%). The greatest contributors to plan
costs PEPM among noninsulin hypoglycemic medications included Actos, Januvia®, and Byetta®.
Medication
Actos
Januvia
Byetta
aWp inflation
∆ net cost (pEpM)
∆ days (pEpM)
9.5%
7.5%
11.4%
6.9%
28.2%
-18.1%
-3.4
19.4
-28.7%
The greatest contributors to plan costs PEPM among insulin therapies included Lantus®, NovoLog®, and Humalog®.
Medication
Lantus
NovoLog
Humalog
aWp inflation
∆ net cost (pEpM)
∆ days (pEpM)
9.2%
11.4%
11.6%
0.5%
30.6%
20.1%
-8.4%
17.5%
6.1%
• New therapeutic options to treat diabetes included the introduction of Onglyza®, a dipeptidyl-peptidase 4 (D-PP4) inhibitor.
• The GAO identified Actos dosages of 15 mg and 30 mg among repackaged brand-name prescription drugs that had
price increases of > 100% between 2000 and 2008.3
• An influential meta-analysis was published in 2007 that suggested a link between Avandia® and a higher risk of
myocardial infarction and mortality.10
- Another study showed that between January 2007 and May 2008, pharmacy claims for Avandia (rosiglitazone)
and combination products containing rosiglitazone decreased from 97.3 per day per million members to 31.8.11
- At the same time, prescriptions for Actos and Januvia remained stable.11
- In 2009, Avandia use continued to decline (-22.3%).
14
> 2010
• In October 2009, Byetta received an indication for monotherapy in type 2 diabetes with a REMS required.12 That
same month, warning and precaution language was added to the Byetta label for postmarketing reports of acute
pancreatitis.13
• In December 2009, new warnings and precautions language was added to the Januvia label for postmarketing reports
of acute pancreatitis.14
• In July 2009, the FDA released an early communication that suggested an increased risk of cancer associated with
Lantus in patients with diabetes; review is pending.15 NovoLog became available for pump infusion that same month.16
2. rESpIrATory drUGS
• Trend: 11.4%
The respiratory therapies include treatments for asthma and chronic obstructive pulmonary disease (COPD; Formulary
Guide Chapters 13.3.1-4, 13.3.6): xanthines, beta-agonists (oral and inhaled), inhaled corticosteroids, and other miscellaneous
pulmonary agents. This category does not include allergy treatments.
Respiratory therapies moved from ninth place in 2008 (9.8%) to the second largest contributor in 2009. Utilization growth
increased dramatically from -2.1% reported last year; however, changes in cost per day of therapy primarily drove trend.
Treatment rate increased by 2.5% and treatment intensity grew by approximately 2%. Data analysis by age group revealed
an inverse relationship between age and utilization: Utilization increased 5.0% for patients < 19 versus 1.0% in patients aged
65+. Rising asthma rates likely account for increased use of respiratory medications in the young. In patients < 19, plans
spend the highest proportion of net costs on drugs in this category (15%). However, the greatest changes in cost per day of
therapy, trend, and net plan cost in dollars, occurred in patients aged 65+.
The greatest contributors to PEPM plan costs for the therapeutic category include Advair Diskus®, Singulair, and Spiriva®.
Medication
aWp inflation
∆ net cost (pEpM)
∆ days (pEpM)
Advair Diskus
Singulair
Spiriva
5.7%
8.7%
13.0%
3.9%
6.9%
15.1%
-1.2%
-1.6%
1.5%
• Sales of budesonide inhalation suspension under an exclusive license from AstraZeneca began in December 2009,
following Teva’s halted at-risk launch 1 year prior.17
• Symbicort® received an indication for the maintenance treatment of COPD.18
• With minimal changes in PEPM days, Singulair and Spiriva cost growth may not have resulted solely from utilization
growth. The GAO identified the Singulair 10-mg dosage (repackaged) as having an extraordinary price increase.3
- Both medications have been the subject of recent FDA safety reviews. Leukotriene inhibitors, including Singulair,
contain label language that associates use with neuropsychiatric events.19
• The FDA Pulmonary—Allergy Drugs Advisory Committee agreed that the data from the Spiriva UPLIFT trial adequately
resolved potential safety concerns about stroke, heart attack, and cardiovascular death that were raised in an earlier
communication (10/2008).20
• In early 2010, the FDA mandated a REMS for all long-acting beta-agonists (including Serevent® and Foradil®).21
15
3. Antiviral drugs
• Trend: 15.7%
Antiviral drugs (Formulary Guide Chapter 1.8) include oral treatments for HIV/AIDS, influenza, herpes, hepatitis C, hepatitis B,
and injectable treatments for respiratory syncytial virus (RSV), and cytomegalovirus.
Although contribution to overall trend is lower this year (13.9% in 2008), the antiviral category remains one of the top
contributors to trend. Treatment rate jumped 38%, coinciding with the H1N1 pandemic, and treatment intensity declined
(-21.0%) likely due to the short course of treatment for or prevention of H1N1. Utilization increased most in the youngest and
oldest patients: 45.7% in patients < 19 and 10.3% in those aged 65+. In patients aged 35 to 49, antiviral drugs are the greatest
expense for plan sponsors, contributing 8.3% to net plan costs.
In 2009, plan net costs grew almost 15% for HIV/AIDS therapies (Chapter 1.8.2) and 12.5% for all other antivirals (Chapter
1.8.1), including treatments for flu.
Antivirals that contributed most to PEPM plan costs include Valtrex, Atripla®, Truvada®, and Tamiflu®.
MedicationAWP Inflation
Valtrex
Atripla Truvada
Tamiflu
12.7%
5.6%
6.6%
9.2%
∆ net cost (PEPM)
∆ days (PEPM)
10.2%
31.0%
23.1%
130.2%
-2.2%
24.6%
15.4%
87.8%
• 2009 antiviral introductions included Agriflu® and Hiberix®.
• A generic version of Valtrex® launched for herpes and became available in late 2009.
• Isentress® received a new indication for treatment-naïve (previously untreated) patients with HIV.22
• Price and utilization increases drove plan spending for Tamiflu in 2009.
• In July 2008, the FDA issued an early communication about an ongoing safety review assessing risk of myocardial
infarction in patients taking nucleoside reverse transcriptase inhibitor (NRTI) antivirals.23 Both Truvada and Atripla
contain an NRTI,24, 25 but these medications were not included in the analysis that prompted the early communication.23
4. ADHD
• Trend: 23.8%
Methylphenidate and amphetamine formulations, Straterra® and Provigil®, along with single-isomer versions, comprise
most of the therapeutic agents in this category (Formulary Guide Chapter 3.9.4).
16
> 2010
The 2009 Drug Trend Report identified the ADHD category as a fast mover. This year, ADHD therapies emerged as the fourth
largest contributor to overall trend with the largest trend (23.8%) of all categories analyzed. Treatment rates increased 19.1%,
while treatment intensity decreased 8.4%. Plan sponsor spending grew 13.2% for ADHD therapies in children. However, the
greatest utilization growth for this category occurred in the 20- to 34-year-old demographic (21.2%). The 2009 trend data for
children < 19 approximated half of the trend for adults aged 20 to 34 (18.9% versus 37.1%). Some of the drugs in this category
are indicated to treat adults with ADHD.
ADHD therapies that contributed the most to PEPM plan costs in 2009 included Concerta® and Adderall XR. Changes in
net cost and days highlight the generic conversion of Adderall XR. Provigil is a stimulant medication indicated for excessive
sleepiness because of obstructive sleep apnea, shift-work disorder, or narcolepsy. Though Provigil is not indicated for
ADHD,26 it resides in this therapeutic category and contributes more to plan costs than any other treatment in the category.
See also discussion in “Demographics of trend.”
Medication
Provigil
Concerta
Adderall XR
aWp inflation
∆ net cost (pEpM)
∆ days (pEpM)
20.8%
1.8%
12.9%
14.0%
12.7%
-27.3%
-6.7%
2.0%
-45.9%
• Two new treatment options for ADHD became available in 2009—a generic formulation for Adderall XR ($1.6B in 2008
sales), and Intuniv™ extended-release tablets.
• In September 2009, Gould et al., published a case-control study funded by the FDA and the National Institute of Mental
Health (NIMH) that suggested a link between stimulant use and sudden death in children.27 In a communication, the
FDA advised that an additional large-scale study investigating cardiovascular risk and stimulant use for ADHD will
conclude in late 2010.28
5. SELECTEd NEUroLoGICAL drUGS
• Trend: 20.1%
Selected neurological therapies (Formulary Guide Chapters 3.5, 3.7) treat Parkinson’s disease, Alzheimer’s disease, multiple
sclerosis (MS), and Huntington’s chorea.
Selected neurological drugs round out the top five contributors to trend. Trend for this category was second highest behind
ADHD, and driven by increased costs per day of therapy. Treatment rate decreased (-7.3%), but treatment intensity grew
10.7%. The highest relative trend contribution appeared in patients aged 65+ (17.9%).
17
Therapies within the category that contributed most to plan costs include: Copaxone®, Aricept, Namenda®, and Mirapex®.
Medication
Copaxone
Aricept
Namenda
Mirapex
aWp inflation
∆ net cost (pEpM)
∆ days (pEpM)
2.5%
11.5%
9.1%
19.1%
37.3%
13.9%
12.8%
23.8%
7.9%
2.2%
4.1%
8.2%
• Copaxone® received a new indication for the treatment of MS after first clinical episode.29
• Patents for Aricept and Mirapex will likely expire in 2010, which should favorably impact plan costs as patients shift to
a generic.
6. rHEUMAToLoGICAL drUGS
• Trend: 13.9%
Rheumatological drugs treat rheumatoid arthritis (RA), lupus, Crohn’s disease, ulcerative colitis, and other autoimmune
diseases (Formulary Guide Chapter 10.3.2).
In 2008, rheumatological drugs were the second largest contributor to overall trend (14.7%). This year, this category
contributed a lower percentage and trend was down from 17.2% in 2008. Utilization grew 12.0%, rising sharply across all age
groups: 18.1% in patients < 19, 21.2% in patients aged 20 to 34, 15.4% in patients aged 35 to 49, 14.6% in patients aged 50 to 64,
and 6.3% in patients aged 65+. Cost per day of therapy increased modestly despite an 8.4% inflation rate for Enbrel® and a
6.3% inflation rate for Humira®. The treatment rate grew 19.2%, while treatment intensity decreased 5.9%. Rheumatological
drugs reside within formulary chapter 10.3, musculoskeletal and rheumatological. This chapter contributed 4.8% to trend.
PEPM costs increased 13.9% in 2009 for this category. Enbrel and Humira drove costs in this category and occupied the third
and sixth places when net plan costs per drug were rank-ordered. Since 2008, PEPM costs for each have increased 4.1% and
26.9%, respectively.
• 2009 marked the introduction of two new therapeutic biologics in this category: Simponi™ for RA, psoriatic arthritis,
and ankylosing spondylitis; and Stelara™ for psoriasis.
• Cimzia® received approval for treatment of RA.30
• Simponi, Stelara, and Cimzia require special handling and are typically dispensed by specialty pharmacies.
• Most drugs within this category act by inhibiting tumor necrosis factor (TNF). In August, the FDA issued a follow-up
communication specifying TNF class-wide boxed warnings against increased lymphoma risk in children and
adolescents.31 In that same communication, the FDA mandated additional language clarifying that prior risk of
malignancies language in the label refers to increased risk of leukemia. The FDA also required label and REMS
medication guide updates to reflect warnings against new-onset psoriasis.
18
> 2010
7. UroLoGICAL drUGS
• Trend: 15.7%
Urological therapies treat benign prostatic hyperplasia (BPH), urinary incontinence, erectile dysfunction, urinary
anesthetics, cholinergic stimulants, anticholinergics, antispasmodics, and others (Formulary Guide Chapter 14).
Urological drugs contributed less to trend in 2009 than in the previous year (10.2%). Utilization grew at a slight pace with
incremental growth in treatment rate (2.2%). Treatment intensity growth remained steady (0.8%). Similar to 2008, cost per
day of therapy grew dramatically (12.0%).
Leading contributors to PEPM plan costs included Flomax and Viagra®, and each showed large increases in net PEPM costs:
29.9% and 16.4%, respectively. AWP increased for Flomax by 25.6% and for Viagra by 16.0%.
• The Flomax patent expired in early 2010, which can offer substantial savings to plans.
8. BiotEchNology drugs
• Trend: 10.4%
• Utilization ∆: -3.4
• Contribution to net plan costs: 3.7%
Biotechnology drugs include interferons, erythroid stimulants, myeloid stimulants, growth hormones, vaccines, and
interleukins (Formulary Guide Chapter 9).
The 2009 Drug Trend Report identified the biotechnology drug category as a fast mover, owing mostly to increased cost
per day of therapy. Utilization decreased overall because of a large increase in number of patients (39.5%) and a relatively
equally large reduction in patient days (-30.6%).
This category comprises a diverse group of recombinant proteins—drugs derived through recombinant DNA technology.
Net costs PEPM for interferons increased 14.4%, while utilization decreased (-4.3%). Growth hormone PEPM costs increased
(10.0%), and utilization increased modestly (3.4%). Net costs increased and utilization growth slowed (-1.0) for myeloid
stimulants. Net plan costs and utilization for erythroid stimulants decreased substantially, -17.0 and -17.6, respectively.
Net costs for vaccines increased 39.3%, likely a result of increased availability and usage of flu vaccine. For example, net
plan costs for FluMist® grew 62.1%, and days increased 43.2%. Although a relatively small cost to plan sponsors, costs for
interleukins more than doubled and utilization increased 43.5%—more than any other class within the category.
Avonex®, Rebif®, and Nutropin AQ® led plan PEPM costs for this category. Net plan PEPM costs increased 14.4%, 20.9%, and
67.6% for these medications, respectively. AWP also substantially increased for all three brands: 21.0% for Avonex, 16.9% for
Rebif, and 7.4% for Nutropin AQ.
19
• New vaccines include Agriflu for influenza types A and B and Hiberix for Haemophilus B.
• New biologics include Ixiaro®, for Japanese encephalitis, and Cervarix®, for prevention of cervical cancer.
• Ilaris®, a new therapeutic biologic, treats cryopyrin-associated periodic syndrome (CAPS).
• Gammaplex® was approved for primary humoral immunodeficiency.
• Humatrope® received an additional indication for short stature in children.32
• The H1N1 pandemic likely contributed to increases in the number of patients treated within this category.
• In April 2009, the FDA concluded its safety review of botulinum toxin therapies, resulting in new warnings across the
class and REMS medication guide revisions.33
• The FDA safety review of erythropoiesis-stimulating agents (ESA) began in early 2008 and may have contributed to
declining utilization within this category since that time.
- In early 2010, the FDA issued a drug safety communication requiring REMS for all ESAs.34
9. ANTICoAGULANT ANd ANTIpLATELET drUGS
• Trend: 10.9%
This therapeutic category comprises anticoagulant agents, antiplatelet agents, and low molecular-weight heparin.
In 2009, anticoagulant and antiplatelet drugs contributed considerably less to trend compared with the previous year. As
well, trend was lower for this category in 2009 (14.0% in 2008), while utilization grew steadily and cost per day increased
markedly. The number of new patients grew 4.2%, but new use was offset by reduced treatment intensity among existing
patients (-3.5%). As patients age, this category contributed a greater proportion to trend, comprising 16.2% in the 65+ subset.
The category contributed minimally to trend in children, but changes in utilization and cost of therapy per day grew at
similar rates (5.0% and 5.9%, respectively). By contrast, as age increased, contribution to trend resulted almost solely from
changes in cost of therapy. In the 65+ age group, utilization grew very little (0.4%), while costs grew 9.2%.
Of all prescription medications, plan sponsors spend the fourth greatest amount PEPM on the antiplatelet drug Plavix and
that percentage increased 11.8% in 2009. Plavix utilization grew incrementally at a rate of 2.8%. The anticoagulant Lovenox®,
also drove plan spending in this category—net cost change PEPM increased 12.3%, while utilization increased 5.5%. Net
plan costs decreased for the anticoagulants Coumadin® and its generic equivalent warfarin (-6.2% and -17.0%, respectively).
Coumadin utilization decreased while warfarin use remained relatively flat: -16.2% and 0.8%, respectively.
• Early and follow-up communications by the FDA advised against coadministration of the antiplatelet drug Plavix and
proton pump inhibitors (PPIs), such as omeprazole (Prilosec®), because the latter inhibits the metabolic conversion of
Plavix to its active form.35
• The FDA issued a public health advisory, stating that coadministration reduces the anticlotting benefit of Plavix.36
• The Medco Clopidogrel Outcomes Study series of analyses showed clinically significant increased relative risk for
major cardiovascular events such as stroke, myocardial infarction, and death in patients taking clopidogrel and PPIs in
cardiovascular patients and those with diabetes. 37, 38
• In March 2010, the FDA added a boxed warning to the Plavix label to warn of reduced efficacy in patients who cannot
metabolize the drug effectively because of genetic variations in the liver enzyme CYP2C19.39, 40
20
> 2010
10. CANCEr ANd TrANSpLANT
• Trend: 7.1%
Cancer and transplant classes include antineoplastics, immunosuppressants, antimetabolites, hormone therapies, and
molecular target inhibitors (Formulary Guide Chapter 2.1)
Cancer and transplant medications round out the top 10 therapeutic categories with the greatest trend contributions.
While utilization growth remained relatively constant, the cost per day of therapy increased. Cancer and transplant drugs
are the third largest contributor to net plan costs among the top 10 trend drivers. Because many cancer medication claims
may be recognized and paid as medical services, this amount underestimates the contribution to plan costs for this chapter.
Treatment of new patients grew 4.9%, but treatment intensity declined by 3.9%. The greatest utilization growth occurred in
children aged < 19 years (4.0%). However, contribution to trend and net plan costs remained low (1.0% and 1.5%, respectively)
for this age group. By contrast, cost per day of therapy rose 7.2% for the 65+ subset and contributions to net plan costs and
trend climbed 5.3% and 10.4%, respectively.
Within this diverse category, net cost PEPM growth occurred in alkylating agents (4.0%), antimetabolites (7.0%),
antiestrogens (14.7%), and antineoplastics (13.6%). However, plan sponsors spent less PEPM on androgens (-95.2%),
hormones (-10.2%), antiandrogens (-23.7), and immunosuppressants (-6.0%). Notable shifts in PEPM net costs occurred
for Xeloda® (14.5%), Arimidex® (14.3%), Femara® (19.4%), tamoxifen (-23.9%), Casodex® (-41.9%), CellCept (-40.3%), Gleevec®
(22.1%), Revlimid® (26.0%), and Sprycel® (59.6%).
• In 2009, several medications within the therapeutic category became available as generic drugs accounting for some
of the aforementioned shifts in plan sponsor PEPM costs.
- First-time generics include CellCept, Prograf, and Casodex.
• New medications include Afinitor® and Votrient® for advanced kidney cancer, Folotyn® for peripheral T-cell lymphoma,
Istodax® for cutaneous T-cell lymphoma, and Arzerra® for chronic lymphocytic leukemia.
• New indications for medications within the category include Avastin® for glioblastoma and first-line treatment of
metastatic kidney cancer,41 and Alimta® for maintenance therapy in non-small cell lung cancer.42
• The Arimidex patent will likely expire in 2010.
> trENd ModErators
Seizure, ulcer and heartburn, and osteoporosis therapeutic categories moderated trend the most in 2009. Figure 6 shows
their contribution to trend, trend growth, utilization changes, and changes in cost per day of therapy.
Blockbuster generic conversions accounted for large trend decelerations in 2009. Generic introductions of Topamax and
Depakote® ER in early 2009 and continued shift to divalproex moderated trend for seizure medications. In this same
category, plans spent considerably less on Keppra® (-64.6%), Depakote® (-79.7%), Lamictal® (67.8%), and Neurontin® (-15.3%).
The generic conversion of the branded drug Prevacid moderated trend in the ulcer and heartburn category. Shifts in therapy
mix to alendronate tablets (the generic equivalent of Fosamax®) continued to moderate trend in the osteoporosis category.
21
figurE 6.
seizure, ulcer and heartburn, and osteoporosis moderated trend
Top THErApEUTIC CATEGorIES THAT ModErATEd TrENd
Trend
4.4
5
Utilization
Cost per day
1.1
0
-5
-3.9
-5.0
-5.6
-8.3
-10
-13.4
-15
-20
-17.2
-20.7
-25
Seizure
Ulcer & heartburn
Osteoporosis
Contribution
to trend (%)
-13.9
-5.9
-5.3
2008 (%)
14.1
5.6
-7.0
Source: Medco data
> catEgoriEs to Watch
lipid-lowering agents
2009 marked a rebound in plan sponsor spending and trend for lipid-lowering agents. Among nonspecialty drugs, lipidlowering agents comprise the greatest single contribution to net plan costs (9.5%)—almost 1 of every 10 dollars spent
on prescription drugs goes toward the category. Overall, trend grew 0.9%, driven by increased PEPM costs (38.5%) and
utilization for Crestor® (22.7%). In 2009, the FDA concluded a review of safety data from the SEAS trial,43 and preliminary data
from the IMPROVE-IT44 and SHARP45 trials advising of an unlikely risk of cancer or cancer-related death in patients taking
Vytorin® or Zetia®.46 The 2011 scheduled patent expiration for Lipitor will likely enable large shifts in therapy mix to generic
formulations. However, many branded and combination products will remain eligible for marketing exclusivity and may
obtain 6-month patent extensions by adding pediatric indications similar to those granted to Crestor and WelChol® in 2009.
antipsychotics
The antipsychotic therapeutic category contributes the 11th greatest percentage to overall trend: 5.9%. Utilization (5.2%)
and cost per day (6.5%) of therapy continue solid growth and trend has been consistently among the highest across all
categories (12.0% in 2009). Continued evergreening, or patent extension, strategies with added pediatric indications (e.g.,
Abilify®, Zyprexa, and Seroquel in 2009), combination use in depression (Seroquel XR®, Symbyax® in 2009), and novel delivery
formulations (Risperdal Consta®) may partially offset savings from scheduled upcoming patent expirations for Seroquel XR
and Geodon® in 2012. Furthermore, many pipeline products may be attractive alternatives to brands and lower-cost generics
because they target effective treatment possibly with fewer extrapyramidal side effects and less weight gain.
22
> 2010
specialty healthcare
The term “specialty” has expanded over time from its original application to include injectable recombinant proteins (drugs
derived though recombinant DNA technology).47 Specialty drugs treat patients with chronic and complex diseases and
typically require special handling by pharmacists, providers, and patients. These patients may also be the largest users of
other, nondrug healthcare services such as physicians, hospitals, and emergency rooms. Healthcare professionals infuse
or inject some specialty drugs while other drugs are self-administered (e.g., treatments for RA).48 Specialty pharmacies
accommodate specialty drug handling requirements and may offer additional services to enhance the patient’s therapeutic
experience. Examples may include patient education services to ease administration, adherence support, and reimbursement
services to help patients navigate insurance paperwork. Recent data suggest an association between specialty pharmacy
management and improved adherence to specialty medications.49 These management services may lead to lower costs
within the healthcare system.
Seventeen of the new drugs approved in 2009 qualify as specialty (see Table 2). By contrast, nine specialty medicines were
approved in 2008.
> pharMacy vs. MEdical BENEfit
Traditionally, specialty drugs treated rare conditions affecting few patients. The special handling, administration, and
patient monitoring requirements contribute to their cost, which can annually amount to tens of thousands of dollars for
patients and tens of millions of dollars for plans. In the last decade, specialty drugs have become available to treat a broader
range of illnesses.
Specialty drugs may be recognized and paid under either the pharmacy or medical benefit. These parallel adjudication
tracks can make it challenging to identify and quantify total costs since they use different coding language, pricing sources,
and provider contracts.47 A recent survey* of plan sponsor perceptions highlighted the implications of these differences. The
study revealed that 77% of decision makers believe that their organization receives more consistent specialty drug pricing
under the pharmacy benefit and that same percent of respondents thought that coverage under the pharmacy benefit
would enable more spending transparency. The costs discussed in this report include specialty drugs adjudicated only under
the pharmacy benefit and so may underestimate the total expenditures on specialty medications.
> 2009 spEcialty drug trENd
In 2009, specialty trend increased 14.7%. Although this was a decrease from 15.8% for the period covering 2008, the last
4 years have marked consistent double-digit growth in specialty trend. Historical data reveal a growing gap between the
relative contributions to specialty trend—utilization and unit cost (see Figure 7). In recent years, unit cost has emerged
as the factor driving specialty trend. Unit costs climbed 12.1% in 2009, compared with 11.5% growth the preceding year.
Utilization growth slowed to 2.6%, compared to the figure reported for 2008: 4.3%.
* The third annual Medco survey on pharmacy benefit management was conducted during 1Q 2009 using web-based technology by Haldy Mcintosh & Associates. respondents
included 300 individuals with pharmacy benefit decision-making responsibilities (e.g., Benefits Managers or Benefits Directors) and included one respondent per organization.
Organization demographics included: 68% corporate (for profit), 13% public sector, 3% union group, 16% nonprofit.
23
figure 7. Utilization and unit cost diverge in specialty
Specialty trend 2006 to present
Trend
specialty change (%) year to year
20
18
16
16.1
15.8
14
10
8
7.3
6
8.8
8.4
4.3
2.6
2
0
12.1
11.5
3.9
4
Unit cost
14.7
12.3
12
Utilization
2006
2007
2008
2009
Source: Medco data
Unit cost growth
Unit costs increased 12.1% compared with 11.5% reported for 2008, primarily because of drug manufacturer price increases.
Unit cost accounted for a higher relative contribution to trend for drugs used to treat MS, growth stimulating agents, and
cancer medications. Unit costs and utilization contributed equally to trend in RA.
Utilization growth
Utilization increased 2.6% compared with 4.3% growth reported for 2008. This year, utilization, as opposed to unit cost,
contributed a greater percentage to specialty drug trend in the disease states pulmonary arterial hypertension (PAH),
immune deficiency and hemophilia, and for anticoagulants as well as pulmonary agents. Several new market entrants may
also have driven utilization increases:
• New options to treat RA (Simponi [golimumab]), and other autoimmune diseases (Stelara [ustekimumab])
• Adcirca® (tadalafil) to treat PAH50
In addition, many specialty medications treat rare diseases that have a large number of undiagnosed patients. As these
patients move from undiagnosed and untreated to diagnosed and treated, they drive total utilization. Examples of these
rare diseases include PAH and alpha-1 antitrypsin deficiency. Both are treated with specialty drugs in the pulmonary category.
24
> 2010
> spEcialty trENd drivErs
figurE 8.
MS, RA and other autoimmune conditions, and cancer remain the three largest contributors to specialty trend (Figure 8).
This year, MS specialty drugs became the leading contributor to specialty trend, up from the second largest contributing
position last year due largely to the 22.7% increase in cost per day for this category. PAH and anticoagulation agents
round out the top five specialty trend drivers. Figure 9 illustrates the percent contribution of each therapeutic category to
pharmacy spending for specialty drugs in 2009.
Ms, ra, and cancer drove specialty trend
SpECIALTy THErApEUTIC CATEGorIES rANkEd by TrENd CoNTrIbUTIoN
Trend
Utilization
Cost per day
40
35
33.2
31.5
30
25
24.7
23.7
22.7
20
17.8
15
14.0
10
5
0
13.4
16.9
15.6
13.1
11.9
8.3 7.9
6.8 6.7
1.6
16.9
21.9
10.1
9.4
6.4
5.8
3.5
1.3
Hemophilia
7.9
5.6
MS
RA
Cancer
PAH
Anticoagulants
Growth agents
Pulmonary
Immune deficiency
Contribution
to specialty
trend (%)
31.1
25.6
15.5
7.0
6.0
4.2
3.5
2.9
2.3
2008 (%)
26.1
30.1
16.5
5.7
6.3
5.9
3.9
2.5
0.5
Source: Medco data
MS = multiple sclerosis. rA = rheumatoid arthritis and includes other immune disorders. PAH = pulmonary arterial hypertension. Spending growth factors multiply to yield total trend,
so utilization growth and cost per day may not be additive.
Multiple sclerosis emerged with the greatest contribution to specialty trend in 2009. Copaxone and Avenox drove trend,
each with substantial increases in net cost PEPM (37.3% and 13.9%, respectively). While utilization (days) increased for
Copaxone 7.9%, it decreased for Avonex (-6.0%).
rheumatological drugs cost plan sponsors the most PEPM and contributed the second greatest percentage to specialty
trend. Enbrel and Humira are leading cost drivers and each had increases in net PEPM cost in 2009 (4.1% and 26.9%,
respectively). Utilization declined for Enbrel (decreasing 3.0%) but grew for Humira (21.1%).
cancer. The rising cost of specialty drugs, particularly for highly prevalent diseases such as cancer, has led industry experts
to spotlight oncology as a priority area for cost-saving measures. In the last 4 years, almost all of the drugs approved for
cancer treatment have cost more than $20,000 for a 12-week course.51 Cancer comprises 15.5% of specialty trend and 16.9%
of plan costs among specialty medications. Because many cancer specialty medications are adjudicated through the
medical claims process, however, these numbers underestimate the true costs to plan sponsors. New, expensive, targeted
biologics are driving cost increases. This pattern will likely continue as more of the approximately 800 cancer products in
development come to market. 44
pulmonary arterial hypertension (pah). Treatments for PAH contributed 7.0% to specialty trend. Utilization for medications
within this class increased 17.0% and costs per day of therapy grew 13.1%. The FDA approved two existing medications to
treat PAH in 2009: Tracleer®52 and Adcirca. The net cost PEPM for Tracleer increased 21.5% and utilization increased 5.5%.
25
Anticoagulants contributed 6.0% to specialty trend.
Within the category, Lovenox drove trend with a 12.2%
increase in net PEPM costs and 5.5% increase in utilization.
The possible generic availability of Lovenox in 2012 could
offer substantial savings to plans in this specialty category.
> Specialty trend moderators
Anemia, hepatitis (mostly hepatitis C), osteoporosis, and
specialty HIV treatments posted negative contributions
to specialty trend in 2009, and each category contributed
< 5% to plan costs. Hepatitis drug utilization decreased
14.3%, while anemia drug utilization decreased 17.6%. In
early 2010, the FDA required all erythropoiesis-stimulating
agents (ESAs), such as Epogen® and Procrit®, to be used
and prescribed with REMS. Continued safety concerns with
these agents may account for sharp declines in utilization.34
> Specialty drug spending growth
figure 9. RA and MS contribute most to plan
costs for specialty
Contribution to net plan specialty costs by category
Neutropenia
2.2%
Hemophilia
2.4%
Hepatitis
2.4%
Infertility
2.4%
Pulmonary
2.8%
Other
9.3%
RA
26.8%
PAH
3.6%
Anticoagulant
5.3 %
Growth agents
5.9%
MS
20.1%
Cancer
16.9%
Source: Medco data
RA = rheumatoid arthritis and includes other immune disorders; MS = multiple
sclerosis; PAH = pulmonary arterial hypertension. Other = all categories contributing
< 2.2% to net plan specialty costs: anemia, HIV, immune deficiency, metabolic disorders,
ophthalmics, osteoarthritis, osteoporosis, respiratory syncytial virus. Percentages are
rounded and may not add up to 100%.
Specialty drugs account for an increasing amount of
total pharmacy dollars spent. In 2009, specialty spending
comprised 14.2% of total PEPM spending. Inflation
contributes heavily to specialty spending growth. 2009 inflation for specialty drugs rose 9.5% for brands, 1.9% for the few
generic drugs available, and 9.4% overall. Plan spending is determined by pharmacy claims. The continued movement of
specialty drugs from medical to pharmacy coverage may provide a clearer picture of plan spending.
Specialty spending growth has outpaced spending for nonspecialty, or traditional medications because:
• A high proportion of newly approved drugs are designated as specialty.
• Unique manufacturing processes make specialty drugs expensive to develop.
• Fewer drugs within a therapeutic category limit competition.
• There may be only one specialty treatment for an orphan condition.
• Few drugs are therapeutically equivalent to others in the category, reducing interchange and related cost savings
opportunities.
• It is more difficult to transition existing patients from one specialty drug to another preferred specialty drug because
often these drugs are large, unique proteins that are not considered interchangeable.
• Most small-molecule specialty drugs are relatively new with few generic alternatives.
• No defined approval pathway exists for follow-on biologics (also known as biosimilars).
• Drugs used to treat cancer represent a large portion of new drugs in both the pipeline and marketplace; most are
specialty drugs and some can cost more than $20,000 for a 12-week therapy course.51
> Specialty designations and trend
When separating specialty trend data from book of business trend data, several factors can impact drug trend for the specialty
group. Major factors can include the therapeutic area scope and the type of drugs included on the specialty drug list. Medco
has historically maintained a relatively narrow specialty drug list. For the time period 2008 to 2009, the Medco specialty
drug list included approximately 190 drugs. Specifically, Medco did not include transplant therapies, atypical antipsychotics,
antiemetic therapies, and most HIV medications. Broader specialty drug lists can moderate reported specialty drug trend if
they 1) include more lower-cost drugs with low or negative growth or 2) include some drugs that are available as generics.
Medco’s specialty trend with the 190 drugs on our specialty list was 14.7%. If Medco’s list were expanded to include the
aforementioned categories, our trend would have been 12.1%. The difference in trend resulted from the additional lowercost medications, which may be included in the lists of other PBMs.
26
> 2010
Medicare trend
Medicare has evolved from its original 1965 mandate of providing health insurance coverage to people aged 65+. Persons
aged < 65 with disabilities, amyotrophic lateral sclerosis (ALS), and end-stage renal disease (ESRD) also qualify for benefits.53
Medicare covers 45.9 million people: 38.3 million aged 65+ and older and 7.6 million people aged < 65 with disabilities.54
Medicare coverage comprises four benefits53
• Part A: Hospital insurance for inpatient treatment paid for by payroll taxes and employer taxes (1.5% each).
• Part B: Supplementary medical insurance that covers physician, outpatient, home health, and preventive services for a
fixed, monthly rate dependent on income.
• Part C: Medicare Advantage programs that enable members to supplement or replace coverage with private insurance.
• Part D: Outpatient prescription drug benefits that stand alone (prescription drug plan or PDP) or are linked with a
Part C plan (Medicare Advantage or MA-PDP).
> MEdicarE spENdiNg groWth
Total Medicare drug trend grew 1.7% in 2009. Plans spent the most PMPM for Nexium®, Lipitor, Plavix, Advair Diskus, Aricept,
and Flomax. Patent expirations for Flomax (2010), Aricept (2010), Lipitor (2011), and Plavix (2012) will offer billions of dollars
in savings opportunities for Medicare-eligible members in the near future.
Medicare Part D trend was 5.2%. Utilization increased 1.5%, while unit costs rose 3.7%. For members enrolled in employerprimary coverage plans, trend was 0.3%. In this population, utilization decreased 2.0%, while unit costs grew 2.3%.
Medication
% net cost ∆ pMpM
% utilization (days) ∆ pMpM
Nexium
Lipitor
Plavix
Advair Diskus
Aricept
Flomax
2.4%
-3.5%
10.2%
4.2%
15.6%
29.2%
-3.8%
-8.3%
1.1%
-0.9%
3.5%
-0.6%
The top five chapters of prescription drug spending for Medicare enrollees in 2009, as measured by percent contribution
to net plan costs, included cardiovascular (29.3%); CNS, neurology, and pain (18.8%); gastroenterology (9.6%); endocrine
and diabetes (9.0%); and respiratory (7.8%). Without exception, these chapters contributed the most to plan costs in 2009
and varied little from figures reported in 2008. Figure 10 shows the percent contribution to Medicare costs across all
therapeutic chapters.
27
> Medicare trend drivers
figure 10. and moderators
Figure 11 shows the categories that made
the largest impact on Medicare trend.
The top three contributors included
diabetes (24.8%), respiratory (23.5%), and
urological (22.7%). Increased cost per
day of therapy drove trend growth in all
Medicare trend drivers.
As with book-of-business trend, antiseizure
medications moderated trend with a
decreased contribution to trend of -7.1%,
largely the result of decreased costs. The
moderating effect on trend of osteoporosis
drugs was amplified within Medicare
(-19.7%), likely a combination of decreased
costs (-9.4%) as more patients switched
from brands to generic alendronate, and
decreased utilization (-8.2%) resulting
from ongoing safety concerns among
patients taking bisphosphonates.
figure 11. Cardiovascular and CNS chapters contributed most
to Medicare plan costs
Therapeutic chapters by percent contribution to Medicare
plan costs
Ophthalmological
2.4%
Anti-infective
2.8%
Other
5.1%
Cardiovascular
29.3%
Urological
5.0%
Musculoskeletal
& rheumatological
5.0%
Antineoplastic &
immunosuppressant
5.2%
Respiratory
7.8%
Endocrine & diabetes
9.0%
CNS
18.8%
Gastroenterology
9.6%
Source: Medco data
Chapters based on Medco 2009 Formulary Reference Guide. Other = categories that contributed < 2.0% in
2009: biotechnology, 1.9%; dermatological, 1.5%; diagnostic and misc., 0.7%; ear, nose, and throat, 0.2%;
obstetric and gynecologic, 0.5%; vitamins, hematinics, and electrolytes, 0.4%. Biotechnology = immunology,
vaccines, and biotechnology.
Diabetes and respiratory categories drove Medicare trend
Therapeutic categories ranked by trend contribution to Medicare plans
Trend
Utilization
Cost per day
20
16.0
15
10
13.8
12.2
10.5
15.7
14.8
13.9
12.0
11.5
9.8
13.1
9.6
9.5
8.0
7.5
6.1
5
2.3
2.0
4.0
2.9
0.2
0
3.4
0.1
-2.6
-5
Contribution
to Medicare
trend (%)
11.0
-4.1
-4.9
Diabetes
Respiratory
Urological
Selected
neurological
Anticoagulant
& antiplatelet
Ophthalmological
Cancer &
transplant
Other
gastrointestinal
Biotechnology
24.8
23.5
22.7
22.1
15.3
9.9
5.6
4.8
4.4
Source: Medco data
Selected neurological therapies (Formulary Guide Chapters 3.5, 3.7) treat Parkinson’s disease, Alzheimer’s disease, multiple sclerosis (MS), and Huntington’s chorea.
28
> 2010
demographics of trend
> agE group variatioNs
Trend analysis by age group revealed the growing influence of younger patients in trend. For the second year, trend in
children has exceeded that for other age groups. Drugs in the ADHD category had the largest trend across all age groups.
Although plans still spend much more on older patients because of higher incidence of chronic and complex diseases,
trend in young and traditionally healthier patients warrants further exploration. Trend (and plan costs) in younger patients,
especially children, will increase as more children are diagnosed with “adult” diseases. In 2009, the FDA approved several
new indications for existing products that have traditionally treated adults.
• WelChol, Crestor—for low-density lipoprotein cholesterol (LDL-C) reduction in children aged 10 to 17 with heterozygous
familial hypercholesterolemia55, 56
• Atacand®—for hypertension in children aged 1 to 1757
• Axert®—for acute treatment of pediatric migraine58
• Protonix®—for erosive esophagitis in patients aged 5+59
• Abilify—for irritability associated with autistic disorder in children aged 6 to 1760
• Seroquel—for schizophrenia in children aged 13 to 17, and for acute manic episodes in children aged 10 to 17 with
bipolar I disorder61
• Zyprexa—for schizophrenia and for acute mania (bipolar I) in children aged 13 to 1762
New indications for traditional “adult diseases” act as a bellwether for the changing face of chronic and complex disease in
the United States and may foreshadow new spending patterns for plan sponsors in the coming decades. Table 4 highlights
the contributions to trend by each age group’s top three therapeutic categories.
TABLE 4.
top contributors to trend by age group
class
ADHD
Antibiotics
Antivirals
Asthma & COPD
Diabetes
Oral contraceptives
Selected neurological
rheumatological
Urological
< 19
20-34
21.6 %
11.9 %
17.3 %
15.5 %
11.8 %
11.3 %
35-49
19.9 %
14.3 %
15.4 %
50-64
65+
14.3%
28.3 %
25.7 %
28.7%
14.6 %
23.4 %
Other categories driving trend in children include dermatological and biotechnology products. For young adults aged 20
to 34, rheumatological medications also increased trend. Other notable trend drivers in ages 35 to 49 include diabetes,
biotechnology, and ADHD. In addition to the categories highlighted in the table, antivirals, selected neurological, and
urological medications increased trend in patients aged 50 to 64. For those aged 65+, selected neurological, anticoagulant
and antiplatelet, and cancer and transplant also drove trend. Antidepressants moderated trend in age groups 20 to 34 and
35 to 49. Seizure medications moderated trend in all groups except 65+. In the latter age group, ulcer and heartburn and
osteoporosis categories also moderated trend.
29
figure 12.
Drug trend driven by youth
Drug trend by age group
12
Trend
Cost per day
10.8
10
Utilization
9.0
8
6
5.5
5.0
4.1
4
4.8
4.8
3.2
2
3.4
3.2
3.1
2.8
1.6
0.2
0
-0.2
-2
19
20-34
35-49
50-64
65+
Source: Medco data
Although prescription drug trend in children and the young is rising, plan spending remains concentrated in older patients
(Figure 12). Interestingly, fewer categories account for a greater proportion of net plan spending in younger patients. For
example, the top five categories ranked according to net plan costs in patients aged < 19 account for 58.9% of total plan
costs in that age group. By contrast, the total contributions for the top five categories in patients aged 65+ account for 48.0%
of total plan cost contributions for that age group. These data suggest that plan sponsors are spending more dollars for a
larger variety of medications in older patients, whereas plan spending is concentrated among a few categories in children.
figure 13.
Plans spend more on elderly
Net plan costs per age group
2,000
$1,833
net plan cost ($)
1,500
$1,243
1,000
$646
500
$233
0
19
Source: Medco data
Does not include subsidy. Numbers rounded to nearest dollar.
30
> 2010
$326
20-34
35-49
50-64
65+
figurE 14.
Figure 13 shows annual net plan costs per member by age group. Figure 14 shows the top categories of drug spending
aligned with age group quintiles. Therapeutic categories included in the chart include the top two contributing to net plan
costs for each age group.
from youth to older patients, plan spending shifts dramatically
CroSS-SECTIoNAL SNApSHoT oF pLAN SpENdING ACroSS AGE GroUpS
ADHD
16
Antidepressants
contribution to net plan costs ($)
14
Antivirals
Asthma & COPD
12
Diabetes
Hypertension
10
Lipid lowering
Oral contraceptives
8
6
4
2
0
19
20-34
35-49
50-64
65+
Source: Medco data
> slEEp dEprivatioN: hiddEN coNsEQuENcEs, hiddEN costs
Many Americans report chronic sleep deprivation. The Centers for Disease Control and Prevention analysis of data from the
Behavioral Risk Factor Survey and Surveillance System (BRFSS) revealed 11.1% of respondents reported insufficient sleep or
rest during the previous 30-day period.63 Figure 15 depicts states grouped into quintiles from highest to lowest overall drug
utilization. There is notable overlap between states with high drug utilization (possibly an indicator of chronic disease)
and the top states in which patients self-reported inadequate sleep in the past 30 consecutive days. Although causes for
inadequate sleep vary, many studies have shown an association between sleep deprivation and chronic disease (e.g., type
2 diabetes).64 Less well known is the association between sleep apnea that causes sleep deprivation, hypoxia, and the
neuroendocrine imbalances that may lead to obesity and chronic disease. 65
A landmark study reported sleep-disordered breathing (indicated by sleep apnea) in 9% of middle-aged women and 24%
of middle-aged men.66 Provigil, a stimulant (in the category with the fourth greatest contribution to trend), ranked highest
in contribution to net plan costs among all drugs in the category (14.0%) and its AWP grew 20.8% in 2009. Provigil26 is
indicated for and used to treat obstructive sleep apnea, a condition highly prevalent in patients with comorbid chronic
disease or risk factors (metabolic syndrome,67 diabetes,64 cardiovascular disease,68 hypertension69) that prevents a good
night’s sleep. Notable overlap exists in states with high utilization, sleep deprivation, and Provigil use.
Patients with chronic diseases such as metabolic syndrome, diabetes, cardiovascular disease, and hypertension often take
multiple medications to manage these diseases but may also be taking medications such as Provigil to compensate for
apnea-induced sleep deprivation and improve daily function—another economic cost of chronic and complex disease.
Figure 15 shows overall drug utilization, Provigil utilization, and sleep deprivation.
31
figure 15.
Drug utilization and sleep deprivation
Highest
DE, KY, ME, AL, OK, IN, PA, WV, TN, SC
High
AR, HI, VA, LA, NC, IL, NH, MS, OH, FL
Medium
MO, GA, CA, NY, IA, KS, MA, RI, NM, VT, MD
Low
CT, NJ, TX, MT, AZ, ID, WY, OR, SD, DC
Lowest
UT, MI, CO, WA, WI, ND, MN, NE, NV, AK
Sources: Medco data; CDC BRFSS63
32
> 2010
Top 20 states for percentage of respondents reporting
30 out of 30 days of insufficient rest or sleep
Top 20 states for days per member for Provigil
National trend
The Centers for Medicare and Medicaid Services (CMS) reviews national spending trend annually and makes new
projections for the coming decade. This section highlights national trends from 2009.
Overall, national healthcare spending grew an estimated 5.7% in 2009 reaching $2.5 trillion.70 Healthcare spending as
a portion of gross domestic product (GDP) climbed to 17.3%—the largest single-year increase on record.70 Spending
growth by public payers (8.7%) outpaced spending growth by private payers (3.0%), for which the economy had a direct
influence: Medicaid enrollment and spending increased as
unemployment figures rose.70 National health expenditures
per person reached $8,046.70 in 2009.70 Figure 16 depicts
estimated national health expenditures for 2009.
figurE 16.
2009 NATIoNAL HEALTH EXpENdITUrES ($ bILLIoNS)70
CMS estimated that prescription drug spending grew
5.2%, up 2.0 percentage points over 2008. H1N1 antiviral
treatments drove an overall utilization rebound from
2008 to 2009, according to CMS estimates. These data are
consistent with Medco book of business analyses.
CMS predicted that economic recovery will drive national
healthcare spending growth following 2010. Until then,
CMS projected a drop in growth from 5.7% in 2009 to 3.9%
in 2010.54 After 2010, total health spending is expected
to increase year to year and reach 7.0% by 2016.54 The
baby boomer transition from private payers to publicly
paid programs will yield slowed growth in the former
and accelerated growth in the latter over the projected
period. Public funds will account for 52% of national health
expenditures by 2019, up from the present 48.6%, according
to CMS estimates.70
cMs estimated national health
expenditures 2009
Other
$393
Hospital care
$761
Investment
$166
Administrative
$163
Prescription drugs
$246
Nursing home care
$144
Home
health care
$72
Physician &
clinical services
$528
Source: Truffer CJ et al., Health Affairs. 2010;29:522-52970
investment does not include research and development expenditures of drug
companies and other manufacturers. Home health and nursing home care include
freestanding facilities only. Administrative includes program administration and net
cost of private health insurance. Numbers are rounded to the nearest billion dollars.
payer
spending growth 2015
spending growth 2019
Public
6.3%
7.6%
Private
7.2%
5.6%
33
WH ErE To
FoCUS NEXT
THE ForCES SHApING TrENd
WhErE to focus NExt
drug trend is likely to continue at low to mid single-digit levels over the next
3 years. a new wave of first-time generics will help counter the impact of pipeline
drugs in the specialty and oncology arenas, as well as the rising costs of treating
obesity-related and chronic disease.
> key developments that will shape changes in utilization and cost:
• Priceinflationforsingle-sourcebrand-namedrugsislikelytocontinueatrecordhigh
levels, especially where competition among brand products is weak or nonexistent.
• Upto50%offuturetrendwilllikelybedrivenbynewandexistingspecialtymedications,
especially monoclonal antibodies, small-molecule oral oncology drugs, and drugs for
orphan conditions.
• Personalizedtherapeuticapproachesthatrelyonbiomarkersandgenomictestingwill
show significant growth.
• Theepidemicofobesityandunhealthylifestylechoicescouldpushtheprevalenceof
diabetes to new heights and further add to the burden of other chronic diseases.
• About$50billioninU.S.branddrugsaleswillopentogenericcompetitionfrom2010
through 2012, creating substantial savings opportunities for plans and members.
• Apathwayforbiosimilarscouldeventuallyleadtonewversionsofsomeblockbuster
protein-based products, but the impact will not likely be experienced for several years.
> adjust your plan to keep pace with projected change.
Plan designs and benefit management policies should keep evolving to manage the new
wave of first-time generics, the latest biomarker and genomic testing strategies, the rising
costs of specialty medications, future biosimilar products, and the promotion of healthier
lifestyle choices.
WHErE To FoCUS NEXT
trend projections
Over the next few years, drug trend will be shaped by modest increases in utilization, high price inflation for single-source
brands, introduction of many high-cost specialty drugs, and potentially significant cost offsets from a new wave of
first-time generics.
Advances in drug development will yield new, higher-cost oral and injectable therapies for the treatment of cancer,
coagulation and platelet aggregation disorders, central nervous system disorders (such as multiple sclerosis, Alzheimer’s
disease, and pain), immune-mediated disorders (such as inflammatory bowel disease), enzyme-deficiency disorders, and
many “orphan” diseases. All this will likely occur in a new milieu of healthcare reform and the emergence of new genomic
and biomarker tests to help guide treatment decisions.
This report examines the impact of about 140 drugs in the pipeline and about 40 first-time generics expected to come to
market over the next few years. Approximately 40% of these pipeline drugs are likely to fall into the specialty category, and
up to 25% could be for orphan diseases.
35
The drugs highlighted in this report will be of significant interest to payers because:
• They may offer effective treatments for diseases that currently lack adequate treatment alternatives.
• Many of the new drugs, especially those in the oncology space, are expected to be costly. They may have been studied
only for certain narrow uses or for small populations of patients, and they may have been marketed based on an
accelerated approval. Careful attention to prior authorization strategies will be needed.
• Some new drugs in the pipeline will use biomarkers or genomic information to help identify patients who could
benefit and to guide dose or product selection. Genomic or biomarker information could be integrated into plan design
to help inform decision making.
• Some new drugs may be more expensive than existing brands or generics, and may offer no clear advantage. Steptherapy protocols may be needed in some cases.
• Some pipeline drugs may be intended for uses that do not typically qualify for coverage under the current benefit
design, such as sexual dysfunction or weight loss. Plans may need to consider whether to exclude some of these drugs
from coverage.
This section provides some highlights of what lies ahead—new pipeline drugs, new indications, first-time generics, possible
over-the-counter (OTC) switches, biosimilars, personalized approaches to pharmaceutical care, and the challenges created
by the epidemic of obesity. These developments will provide a strong incentive to implement new plan designs, coverage
management programs, and state-of-the-art member engagement programs.
> Trend forecast: The next 3 years
Medco expects the average drug trend for plan sponsors to increase between 3% and 6% annually over the next 3 years
(Table 1). These projections are computed at the ingredient-cost level, unadjusted for future changes in discounts, rebates,
cost sharing, and Medicare retiree drug subsidies. As in last year’s report, Medco has based its projections on ingredient
costs rather than on Average Wholesale Price (AWP), because generic dispensing rates are at record high levels and AWP
pricing does not reflect true ingredient costs for generics. Also, AWP may soon be replaced by another cost benchmark.
Ingredient-cost trend should more accurately reflect the impact of the large number of drug products expected to go
generic in the next 3 years.
Drug trend projection for 2010–2012*
table 1. Year
Utilization increase
Price and mix increase
Annual total
2010
2011
2012
0% to 1%
3% to 4%
3% to 5%
0% to 1%
4% to 5%
4% to 6%
0% to 1%
4% to 5%
4% to 6%
*Projected change in drug spending on a plan ingredient cost per-member per-year (PMPY) basis
As in the past, plan sponsors with less aggressive coverage management and plan design strategies are likely to
experience a drug trend toward or above the upper limit of the projected range. Plan sponsors that adjust coverage
policies by expanding incentives for generic utilization and mail-service programs and adjust member cost-share to keep
pace with current costs may experience spending growth toward the lower limit of this range or even lower.
Unit-cost growth, set by the balance between high price inflation for single-source brands and low price inflation for
generics, is expected to outpace utilization growth as the most impactful trend component over the next 3 years. Unit-cost
increases are expected to account for about 75% of drug trend during this forecast period, with utilization accounting for
the remaining 25%. In 2009, brand price inflation was at an all-time high of 9.2%, and price inflation among generics was
only 0.3%. The rapid price inflation for brand-name drugs is expected to continue over the next 3 years. This inflationary
pressure will be strongly offset by increased use of generic drugs, which could account for about 75% of overall prescription
volume by the end of 2012.
36
> 2010
forEcastiNg trENd
WhErE to focus NExt
Anticipated market developments are combined with 3-year historical utilization and ingredient-cost data to
provide forecasts for the following components of drug trend:
• utilization—changes in the number of users and the number of days of therapy per user
• Mix—changes in unit cost because of shifts in market share from brands to generics, from generics to
brands, and between brands in the same category
• price—changes in unit cost because of increases in manufacturers’ prices for existing drugs
The 2010 to 2012 drug trend forecast is based on utilization and cost data over a 3-year historical period
(2007 to 2009) for a large set of clients with integrated retail and mail-order benefits. The average monthly
enrollment in the data sample was over 40 million members. This year’s projections include members who
enrolled in Medicare Part D plans.
> kEy trENd drivErs
The trend projections provided in this section include many factors likely to affect future unit costs and utilization, including:
• New specialty and traditional drug approvals
• Shifting patterns in drug development away from small-molecule nonspecialty drugs and toward higher-cost,
large-molecule protein-based drugs
• New or expanded indications for existing drugs
• Price inflation among single-source brands
• New dosage forms and combination products
• Increased use of biomarker and pharmacogenomic testing
• Patent expirations and first-time generics
• Expected OTC conversions
• Research findings and clinical recommendations likely to affect prescribing practices
• Changes in disease prevalence, disease recognition, or diagnostic and treatment criteria
Over the next 3 years, about 72% of drug cost trend will be driven by drugs in just 6 of the 16 broad chapters in the
preferred prescriptions® Formulary (Figure 1). The central nervous system (CNS) and endocrine and diabetes chapters will
account for almost 40% of this spending growth.
One important difference between this year’s and last year’s report is the trend impact from the cardiovascular chapter. This
therapeutic area represents a large share of total drug spending (about 20%), but it will be a less significant contributor to
drug trend over the next 3 years, accounting for just 7% of total projected drug trend. The existing generics in this chapter,
the patent expiration of Lipitor® in the cholesterol-lowering class, and several new generics in the angiotensin II receptor
blocking (ARB) class will contribute to this shifting pattern of trend drivers. Detailed projections at the ingredient-cost level
for the top therapeutic chapters begin on page 47.
Within these broad chapters of drugs, eight specific drug categories—including diabetes treatments, rheumatological
drugs, treatments for respiratory conditions, anticoagulant and antiplatelet therapies, cancer treatments, and drugs for
Alzheimer’s disease, and multiple sclerosis—will account for almost two-thirds of ingredient-cost growth over the next
3 years (Figure 2).
37
figure 1. Top therapeutic chapters contributing
to projected drug trend (2010–2012)
figure 2.
Top therapeutic categories contributing
to projected drug trend (2010–2012)
Oral & injectable
diabetes
14%
CNS: Neurology,
mental health & pain
19%
Other chapters
21%
Rheumatological
10%
Other classes
36%
Cardiovascular
7%
Endocrine
& diabetes
18%
Infectious disease
8%
Respiratory
8%
Antipsychotics
4%
Interferons
6%
Musculoskeletal
& rheumatological
10%
Oncology
9%
Source: Medco projection.
Source: Medco projection.
Data are expressed as a percentage of the total projected increase in plan ingredient cost.
WHERE TO FOCUS NEXT
Respiratory
9%
Misc.
neurological*
7%
Cancer
7%
Anticoagulant &
antiplatelet
7%
Data are expressed as a percentage of the total projected increase in plan ingredient cost.
T H E F OR C E S S H A P I N G T R E N D
Marketplace projections
> National drug trend
The Centers for Medicare & Medicaid Services (CMS) reported that national healthcare spending growth slowed to 4.4%
in 2008.1 Spending growth for prescription drugs declined to an all-time low of 3.2%—continuing the deceleration that
began in 2000, and yielding the lowest rate of drug spending growth since 1963. However, the healthcare portion of gross
domestic product (GDP) continued to grow—reaching 16.2% in 2008, up from 15.9% in 2007.1
According to CMS, the record low growth in prescription drug spending can be attributed to several factors, including a low
number of new product introductions, safety-related concerns with certain medication classes, increased use of generics,
and patients either not filling prescriptions or adopting pill-splitting as a cost saving maneuver.1
CMS predicts that the average annual increases in national drug expenditures will be about 6.3% over the next 10 years.
Growth in national drug expenditures is expected to be 5.2% in 2009, a noteworthy increase over 2008. The CMS trend for
2009 is a projection, rather than the actual result for the year, and the projection is somewhat higher than the average
trend of 3.7% that Medco clients experienced in 2009. CMS projects that national drug trend will be 5.6% in 2010, then slow
to 4.7% in 2012 and 5.4% in 2013 due to the introduction of many first-time generics in these years, and then accelerate
again to 7.3% by 2019.2 Price increases for single-source brand drugs are expected to account for about half of the growth
in prescription drug spending during the next 10 years.2
> Drug pipeline
Approximately 140 new drugs, new dosage forms, and new combination products are currently awaiting approval by the
Food and Drug Administration (FDA). About 600 new drugs are in Phase III or Phase II/III clinical trials in the United States,
about 1000 drugs are in Phase II development, and about 1100 are in Phase I/II or Phase I development.3 About one-third
to one-half of the products in Phase III development are new molecular entities (NMEs), new therapeutic biologics, or new
vaccines/blood products. The remainder involve new indications for existing drugs, new combination products, new dosage
forms, or new routes of administration.
38
> 2010
> NEW drug approvals
Across all the drugs in the pipeline, an average of 30 to 40
new drug and biologic approvals are possible in each of the
next 3 years. In 2009, the FDA approved 34 new drugs and
biologics, three more than in 2008. The Center for Drug
Evaluation and Research (CDER) approved 19 NMEs and six
therapeutic biologics, and the Center for Biologic Evaluation
and Research (CBER) approved nine new Biologic License
Applications (BLAs) for vaccines and blood products, for a
total of 34 new approvals.5 , 6 These approvals do not include
several older drugs which have been on the market for
years, but have finally received FDA approval—including
colchicine (Colcrys®), a pancreatic enzyme replacement
product (Creon®), and a new version of interferon beta-1b
(Extavia®). Among the new drug approvals in 2009, almost
50% were for drugs that fall within the specialty category,
and five of the approvals (about 15%) were for new drugs
to treat cancer.
As in 2008, many of the approval delays in 2009 may be
attributable to the increased emphasis on risk evaluation
and mitigation strategy (REMS) programs. The FDA is using
its powers under the FDA Amendments Act to require more
of these programs for new and existing drugs. Since the REMS
requirements started in March 2007, the FDA has invoked
this new authority at least 60 times. Although 47 of the
new programs have involved only a medication guide, 16
have required a communications plan, elements to ensure
safe use (ETESU), or both.7 REMS programs requiring ETESU
can allow drugs to come to market that might not otherwise
have been approved. For example, Sabril® (vigabatrin) was
approved with a REMS program that included an ETESU
component, due to the risk of serious retinal adverse events
associated with this drug that can result in irreversible
partial blindness.
figurE 3.
WhErE to focus NExt
The world’s top pharmaceutical companies have about 2,300 drugs in clinical development in the top 10 therapeutic
categories (Figure 3).3 Oncology drugs will continue to be by far the largest area of new drug development, and they already
represent the largest drug category in terms of worldwide sales. Sales of oncology drugs are growing at 12% to 15% per year
and are expected to reach $80 billion worldwide by 2012.4 Many of the newly approved oncology drugs may use genetic or
biomarker information to determine the appropriateness of a particular therapy for a specific patient.
drugs in development by therapeutic
area (2009)
number of drugs in development
Cancer
831
CNS
329
Infections
229
Pain &
inflammation
204
Cardiovascular
191
Diabetes &
metabolism
166
Respiratory
disorders
Gastrointestinal
137
97
Blood disorders
83
Dermatological
66
Source: R&D Directions 3
The figure shows the number of drugs in the pharmaceutical pipeline for the top 10
areas of development, including drugs in Phase i, Phase ii, and Phase iii, or awaiting
fDA approval.
> futurE BlockBustErs
In 2007, the number of billion-dollar blockbuster drugs fell from 52 to 48 because of the introduction of first-time generics
for some major brands.8 This pattern is expected to continue as many more blockbuster drugs lose their patent protection
over the next few years. Unfortunately, the same will not be true for blockbuster biologics in the specialty arena, as there
is no pathway for approval of lower-cost versions of these drugs at the present time.
Although many current blockbusters will become available in generic form, this trend will be partially offset by the
introduction of new drugs that may become blockbusters, including rivaroxaban, apixaban, and dabigatran (new oral
anticoagulants); ticagrelor and thrombin receptor antagonist (SCH 530348) (new antiplatelet therapies); denosumab
39
(an injectable biologic for osteoporosis and bony metastasis); naproxcinod (a novel nonsteroidal anti-inflammatory
drug [NSAID]); belimumab (a monoclonal antibody for treatment of systemic lupus erythematosus); anacetrapib and
dalcetrapib (agents that lower LDL cholesterol and raise HDL cholesterol); and tanezumab (a novel monoclonal antibody
that blocks nerve growth factor and will be used for osteoarthritis, chronic lower back pain, and interstitial cystitis).
> New indications
Expanding the labeled indications for currently approved drugs, a practice that seems to be particularly common in the
area of specialty and cancer drugs, continues to be a focus for product development. Gaining a new indication expands the
current market or creates a new market for an existing product at lower cost to the manufacturer than developing a new
drug. Although these drugs are often prescribed off-label before the new uses are approved, the new indications represent
significant new user populations, which will contribute to rising utilization.
Some of the new uses being pursued by pharmaceutical manufacturers are shown in Table 2. Many of these new
indications, if approved, could have a significant impact on utilization growth and spending growth over the next several
years. For example, approval for new indications are being sought for Avodart® (prevention of prostate cancer), Cymbalta®
(treatment of osteoarthritis and lower back pain), Pristiq® (fibromyalgia and treatment of postmenopausal symptoms), and
Nuvigil® (jet lag syndrome).
New dosage forms and combination products
New extended-release dosage forms, combination products, and drug-delivery systems continue to be a significant part of
product development. Examples include naproxen/esomeprazole, choline fenofibrate/rosuvastatin, fluticasone/formoterol,
tamsulosin/dutasteride, and several abuse-resistant narcotic analgesic products. Some of these new products will compete
for market share with existing or soon-to-be-released generics.
�The increasing trend impact of specialty drugs
The specialty category includes a very large and diverse group of recombinant and plasma-derived protein-based drugs
and small-molecule drugs used to treat cancer and mostly rare diseases. Specialty drugs now account for about 14% of
plan spending and will become increasingly important as a trend driver over the next 3 years. In 2009, about 40% of drug
trend was attributable to the rising costs for specialty drugs, although the category as a whole represents only about 1% of
prescription claims volume.
Spending in the specialty category has been growing at about 15% per year for the past 4 years, a rate that is several times
faster than overall drug trend. At the current rate of spending growth, specialty drugs could represent 17.5% (about onesixth) of plan drug spending by the end of 2012. As patents expire on many small-molecule blockbuster drugs over the next
3 years, future blockbusters will increasingly come from protein-based and specialty drug products. In 2009, the specialty
category included 13 blockbuster drugs, such as Aranesp®, Avastin®, and Enbrel®, each with more than $1 billion in annual
U.S. sales.
> Orphan drugs
Since passage of the Orphan Drug Act about 25 years ago, about 350 orphan drugs or orphan indications for existing
drugs have been approved. Orphan conditions are rare diseases affecting less than 200,000 patients, and they include
such conditions as hypereosinophilia, hereditary angioedema, multiple sclerosis (MS), myelofibrosis, Huntington’s disease,
urea cycle disorders, inherited enzyme deficiencies, and many others. The Orphan Drug Act provided an expedited path for
approval of drugs to treat these conditions.
There are more than 6,000 rare or orphan diseases that affect about 25 million Americans, and many of these diseases
will continue to be targets for drug development.9 The number of drugs with new orphan designations rose from 208 in
the 3-year period 2000 to 2002 to 425 in 2006 to 2008.10 Since 2006, almost one-third of new NME and BLA approvals
have been for drugs with orphan drug status for one or more indications. Among the new NMEs for biologics approved
in 2009, 13 (38%) were drugs with orphan status for at least one indication. In addition, more than 300 drugs for orphan
conditions were in development in 2007.9
40
> 2010
table 2.
some new indications pending fda approval and in phase iii clinical trials
generic name
New indication
Acthar® gel
Afinitor®
Amitiza®
Arcalyst®
Avastin®
corticotropin gel
everolimus
lubiprostone
rilonacept
bevacizumab
Avodart®
Azilect®
Cymbalta®
Fentora®
gammagard®
dutasteride
rasagiline
duloxetine
fentanyl buccal tablet
intravenous gamma
globulin
adalimumab
ambrisentan
ranibizumab
sorafenib
romiplostim
armodafinil
eltrombopag
desvenlafaxine
methylnaltrexone
bromide
lenalidomide
rituximab
sunitinib malate
erlotinib
nilotinib
temsirolimus
bosentan
lapatinib
pazopanib
rifaximin
sodium oxybate
vorinostat
infantile spasms
Neuroendocrine tumors, carcinoid tumors
Opioid-induced bowel dysfunction
Prevention of gout flares in patients initiating urate lowering therapy
Prostate cancer, refractory ovarian cancer, in combination with Tarceva®
as second-line for non–small-cell lung cancer
reduction in risk for prostate cancer
Slow progression of Parkinson’s disease
Chronic lower back pain, osteoarthritis pain
Breakthrough pain in patients with chronic non-malignant pain
Mild-to-moderate Alzheimer’s disease
Humira®
Letairis®
Lucentis®
Nexavar®
Nplate®
Nuvigil®
Promacta®
Prestiq®
Relistor®
revlimid®
rituxan®
Sutent®
Tarceva®
Tasigna®
Torisel®
Tracleer®
Tykerb®
Votrient®
Xifaxan®
Xyrem®
Zolinza®
WhErE to focus NExt
Brand name
ulcerative colitis, asthma
interstitial pulmonary fibrosis
Diabetic macular edema
Non–small cell lung cancer, malignant melanoma
Chemotherapy-induced thrombocytopenia
Jet lag syndrome, excessive sleepiness associated with Parkinson’s disease
Hepatitis C induced thrombocytopenia
Neuropathic pain, postmenopausal vasomotor symptoms
Opioid-induced constipation in patients with chronic pain
Chronic lymphocytic leukemia, non-Hodgkin’s lymphoma
relapsing-remitting multiple sclerosis, systemic lupus erythematosus
Breast, lung, prostate cancer
first-line for non–small cell lung cancer in Egfr mutations, colorectal cancer
first-line for CML
Mantle cell lymphoma
idiopathic pulmonary fibrosis
Head and neck cancer, first-line for breast cancer, gastric cancer
Breast cancer, sarcoma
Hepatic encephalopathy, diarrhea-associated irritable bowel syndrome
fibromyalgia
Mesothelioma
In October 2009, the National Institutes of Health (NIH) announced a second phase expansion of the Rare Disease
Clinical Research Network (RDCRN), including $117 million in funds for 19 new research consortia. This new funding will
support study of the natural history, epidemiology, diagnosis, and treatment of more than 95 orphan diseases. The RDCRN
manages a program that aims to create specialized infrastructure to further support rare or orphan diseases research.11
Because orphan drugs are intended for use in patient populations where few, if any, treatments are available, they tend to
receive favorable treatment from the FDA and may be ushered more quickly through the review process. In fact, in early
2010 an FDA advisory board recommended approval of an orphan drug, carglumic acid, for treatment of a specific urea cycle
disorder without a single randomized controlled study to support its efficacy.12 This recommendation was likely a result of the
rarity of this disorder and the profound treatment effect that was demonstrated with this drug for an otherwise fatal illness.
Orphan drugs often come to market with a narrow indication for a small population of patients, and generally with a very
high price tag. Their distribution is often restricted to specialty pharmacies. These drugs should generally be included in a
coverage management program to help ensure that utilization is limited to the circumstances where the drugs have been
shown to be effective.
41
> Rx-to-OTC switches
The conversion of prescription drugs to OTC status is a continuing trend. Past OTC conversions have exerted a significant
impact on trend in some key categories, such as the nonsedating antihistamine and proton pump inhibitor (PPI) categories.
OTC versions of the lower dosage strength of Prevacid® (lansoprazole) came to market in late 2009. In the near future, an
OTC version of Zegerid® (omeprazole) is also expected. Thus, three OTC products representing two different PPIs could be
on the market in the near future, including the earlier OTC version of Prilosec® (omeprazole). OTC conversion of two more
nonsedating antihistamines, Clarinex® (desloratadine) and Allegra® (fexofenadine), is also expected in the near future.
As more drugs are converted to OTC status, drug utilization review (DUR) for OTC drugs, dietary supplements, and
prescription products will become increasingly important. Medco has created a DUR system for members who purchase
OTC products from the Medco Health Store™. The system alerts purchasers when an OTC product they are purchasing for
long-term use may have an important drug-drug interaction with another OTC product or a prescription product that they
are also taking. This can help avoid some incompatibilities between OTC and prescription products.
> First-time generics
Drugs with total 2009 U.S. sales of about $50 billion could lose patent protection over the next 3 years, expanding in an
almost unprecedented manner the market for lower-cost generics. The new generics will provide a significant opportunity
for savings to help offset the rising costs of specialty drugs and new drug introductions during the same time period.
Many of the anticipated patent expirations and first-time generics over the next 3 years are shown in Table 3. The number
of first-time generics could be even greater than presented in this table if generic manufacturers continue to launch new
generics on an at-risk basis (before patent disputes are settled) or secure favorable outcomes in ongoing patent litigation.
The potential first-time generics do not include protein-based drugs or biologics with expired patents or those that could
lose patent protection in the next 3 years, since an approval pathway for biosimilar products has not yet been defined.
New regulations for “pay-for-delay” agreements could accelerate the availability of new generics. In current pay-for-delay
agreements, a brand manufacturer compensates a generic manufacturer if the generic manufacturer agrees to drop patent
litigation and delay a generic launch until a specified later date. Congressional action may bring an end to these increasingly
common agreements (there were 19 such deals in 2009) and speed the pace of generic introductions.15
The launch of many new, high-volume generics over the next 3 years will help drive down unit-cost growth in several
therapeutic categories as utilization shifts to lower-cost generic options. The generic conversions will create many
opportunities to shift usage to new generic equivalents and new generic alternatives. A generic equivalent is a generic
drug that includes the same active ingredient and dosage form as the original brand-name product. A generic alternative
contains a different active ingredient, but one that can be used effectively and safely to treat the same condition as a
single-source brand. For example, a first-time generic for Xalatan®, a drug used to treat glaucoma, could provide a generic
alternative to Travatan® or Lumigan®.
In the next 3 years, first-time generics will become available in several drug classes that now include only single-source
brand-name drugs. These drug classes include ARBs with the introduction of generics for Cozaar®, Hyzaar®, Diovan®,
Diovan HCT®, Atacand®, and Atacand HCT®; selective alpha-adrenergic blockers with the introduction of generics for
Flomax®; aromatase inhibitors with the introduction of generics for Femara® and Arimidex®; antiplatelet therapies with the
introduction of generics for the mega-blockbuster Plavix®; and leukotriene antagonists with the introduction of generics
for Accolade® and Singulair®. A first-time generic in a drug class that is considered to be therapeutically homogeneous can
provide a significant savings opportunity as a generic equivalent and a generic alternative within the class.
As first-time generics become available, new brands and combination products are often introduced in the same or
related therapeutic classes. These competing products can counter some of the savings that could otherwise be realized.
For example, the savings from new generics for Fosamax® (alendronate) in 2008 could be reversed by the approval of
the specialty drug denosumab in 2010. Similarly, the potential savings from first-time generics for Aricept® could be
compromised by the introduction of Aricept extended release.
42
> 2010
table 3.
some potential patent expirations for 2010–2012
Brand name (generic name),
manufacturer/marketer
2010
Effexor XR® (venlafaxine extended-release), wyeth
Flomax® (tamsulosin),b Boehringer ingelheim
Aricept® (donepezil), Pfizer
Cozaar® (losartan), Merck
Arimidex® (anastrozole), AstraZeneca
Hyzaar® (losartan/HCTZ), Merck
Mirapex® (pramipexole), Boehringer ingelheim
Aldara® (imiquimod topical cream), graceway
Differin® (adapalene topical),b galderma
Astelin® (azelastine nasal spray), Meda
Fosamax® Plus D (alendronate/cholecalciferol)
2011
Lipitor® (atorvastatin), Pfizer
Zyprexa® (olanzapine), Lilly
Xalatan® (latanoprost ophthalmic solution), Pfizer
Protonix® (pantoprazole), wyeth
Femara® (letrozole), Novartis
Caduet® (amlodipine/atorvastatin), Pfizer
Patanol® (olopatadine ophthalmic solution),b Alcon
Accolate ® (zafirlukast),b AstraZeneca
2012
Plavix® (clopidogrel), Sanofi-Aventis
Seroquel® (quetiapine), AstraZeneca
Singulair® (montelukast), Merck
Actos® (pioglitazone),b Takeda
Lexapro® (escitalopram), forest
Levaquin® (levofloxacin), Ortho-McNeil
Diovan® (valsartan), Novartis
Diovan HCT® (valsartan/HCTZ), Novartis
TriCor® (fenofibrate), Abbott
Lovenox® (enoxaparin), Sanofi-Aventis
Lidoderm® (lidocaine) patch, Teikoku
Viagra® (sildenafil), Pfizer
Geodon® (ziprasidone), Pfizer
Provigil® (modafinil), Cephalon
Lunesta® (eszopliclone), Sepracor
Avandia® (rosiglitazone), glaxoSmithKline
Avapro® (irbesartan), Sanofi-Aventis
Avalide® (irbesartan/HCTZ), Sanofi-Aventis
Avandamet ® (rosiglitazone/metformin),
glaxoSmithKline
Clarinex® (desloratadine), Schering
Atacand® (candesartan), AstraZeneca
Atacand HCT® (candesartan/HCTZ), AstraZeneca
uses
2009 u.s.
retail sales
($M)
Depression, anxiety, panic disorder
Benign prostatic hypertrophy
Alzheimer’s disease
High blood pressure
Breast cancer
High blood pressure
Parkinson’s disease, restless
legs syndrome
Actinic keratosis, genital warts,
skin cancer
Acne
Allergic rhinitis
Osteoporosis
$2,554
$1,718
$1,464
$771
$697
$584
$417
High cholesterol
Schizophrenia, bipolar disorder
glaucoma, ocular hypertension
Stomach ulcers, gErD
Breast cancer
High blood pressure and
high cholesterol
Allergic conjunctivitis
Asthma
$6,053
$1,968
$519
$497
$461
$362
Prevention of arterial
thrombotic events
Schizophrenia, bipolar disorder
Asthma, allergic rhinitis
Type 2 diabetes
Depression
Bacterial infections
Hypertension, CHf
Hypertension
High triglycerides
Treatment/prevention of venous
thromboembolism
Postherpetic neuralgia
Erectile dysfunction
Schizophrenia
Narcolepsy, idiopathic
hypersomnolence
insomnia
Type 2 diabetes
Hypertension
Hypertension
Type 2 diabetes
$4,562
Allergic rhinitis
Hypertension, CHf
Hypertension
WhErE to focus NExt
possible patent
expirationa
$412
$282
$209
$123
$256
$44
$3,482
$3,465
$2,782
$2,554
$1,632
$1,469
$1,376
$1,350
$1,245
$1,064
$1,000
$975
$966
$804
$436
$413
$359
$207
$207
$162
$77
Sources: iMS Health (retail sales),13 Orange Book 14
a
Availability dates for first-time generics are subject to significant change as a result of multiple patent protections, patent litigation, pediatric or other exclusivities, at-risk
launches, and delays between patent expiration and launch of first-time generics.
b
Possible patent expiration assumes a pediatric extension.
43
> Chronic disease and the epidemic of obesity
The high cost of caring for individuals with chronic disease is one of the most pressing healthcare issues in the United
States today. Treatment of chronic diseases accounts for the majority of healthcare spending, so reducing the cost and
burden of chronic disease needs to be a primary focus of payers and other stakeholders in the current healthcare system.
The prevention and treatment of many chronic diseases relies primarily on long-term drug therapies, so the escalating
burden of chronic disease has a direct effect on prescription drug spending.
Contributing substantially to the existing and future burden of chronic disease is the epidemic of obesity and the problem
of inactivity. During the past 40 years, the population of obese or overweight people in the United States has steadily
increased. In the early 1960s, about 31% of males and females were considered overweight and 13% were considered to be
obese. By 2008, these numbers had grown significantly, with 68% of adults being overweight and 33.8% of adults being
obese.16 The numbers for adolescent and school-age children are equally alarming, with about 32% of children being
overweight and 17% being obese.17
Obesity is a risk factor for a variety of chronic conditions, including diabetes, hypertension, high cholesterol, stroke,
osteoarthritis, musculoskeletal disorders, heart disease, sleep apnea, gallbladder disease, lower-back pain, and even certain
cancers. Medical spending for obesity-related conditions accounted for an estimated 10% of total U.S. healthcare costs in
2008, or about $147 billion, according to the Centers for Disease Control and Prevention (CDC).18 Of all chronic diseases, type
2 diabetes is most clearly linked to obesity. In 2009, an estimated 19.5 million adults between the ages of 24 and 85 had
diagnosed diabetes and another 4.25 million were undiagnosed. Over the next 25 years, the number of Americans with
diabetes will climb to an estimated 44 million, and the annual medical spending related to diabetes will increase from $113
billion to a staggering $336 billion.19
Recent data suggest that the rate of increase in the number of people who are overweight or obese has moderated in the
last few years; however, it is still increasing, albeit at a slower pace than in the past.16 Even at the current rate of increase,
overweight and obesity will likely rival smoking as a major public health problem, counteracting the benefits seen from the
decline in smoking over the past several decades.20
All stakeholders in the healthcare system have an incentive to help reduce the impact of overweight and obesity as
contributors to the burden of chronic disease and the corresponding healthcare costs. The solutions will not be simple,
because unlike other risk factors that might be successfully mitigated by drug therapies or shorter-term interventions,
dealing with obesity involves difficult-to-maintain and permanent lifestyle changes. Education on the risks of being
overweight, nutritional counseling, programs to encourage weight loss and increase physical exercise, and reduction in salt
intake are all important components of a plan to reduce the burden of obesity.
The currently available weight-loss drug therapies generally have limited evidence for a long-term impact on obesity.
However, they may be helpful in the short term when combined with lifestyle changes. There are currently at least three
new weight-loss products in the pipeline, including locaserin, naltrexone/topiramate, and naltrexone/bupropion sustained
release. Whether these drugs will provide better options for weight loss is unclear at this time. However, pharmacotherapy
is rarely, if ever, the long-term solution for this issue, and lifestyle changes are always needed.
Utilization of cardiovascular drugs will be affected by the rise in obesity-related illnesses, but these drugs are not expected
to be a major trend driver over the next 3 years, due to the impact of new generics for many drugs used to treat hypertension
and high cholesterol. However, drugs to treat diabetes will be a major driver of trend, and the rising prevalence of obesityrelated diabetes will move the needle even further.
> Progress in personalized medicine
Personalized medicine, or pharmacogenomics, refers to drug therapy tailored to the specific characteristics of an individual
patient. Gene-based and other molecular diagnostic tests provide the information that enables this more personalized
approach. Although integration of genomic technology into day-to-day healthcare will take years to achieve, progress over
the next few years will begin to have a significant effect on drug utilization.
44
> 2010
WhErE to focus NExt
illuminating the mechanisms of disease
Advances in gene-sequencing technology will continue to be a major driver of personalized medicine. Gene sequencing
that would have cost millions of dollars several years ago may be widely available for under $1,000 in the next few years. In
2009, the National Human Genome Research Institute awarded millions of dollars in grant funding to stimulate research
and development in genomic technology that can sequence a human genome at much lower cost. Several companies are
currently racing to become the first company to offer full genome sequencing for under $1,000.21, 22
Inexpensive full-genome sequencing will provide a wealth of individualized data that can be used throughout a person’s
lifetime to help inform clinical decision-making. The availability of such technology has already resulted in an explosion of
genetic literature in recent years; this trend is expected to continue or even accelerate over the next few years.23 The new
genetic information will provide hope for illuminating mechanisms of disease that were previously a mystery and help
identify at-risk populations where therapeutic interventions might be helpful. Still, one of the primary challenges will be
linking the wealth of information on a wide variety of genotypes to discernible levels of risk for development of a disease
or condition, as well as developing personalized interventions or pharmacologic treatments that will forestall development
of the at-risk condition.
pharmacogenomic pipeline
To capitalize on the availability of genetic information, pharmaceutical companies are either developing their own
molecular diagnostic divisions or are partnering with companies that can provide diagnostic testing capabilities for drug
development.24, 25 Genetic and other biomarkers are being used to identify the target patient populations for pipeline drugs
during clinical development. These tests may eventually be marketed as “companion diagnostics” when the drugs are
approved by the FDA.
However, regulatory requirements for drug and diagnostic co-development are unclear at the present time. Diagnostic
companies and pharmaceutical manufacturers, as well as trade organizations, have been actively lobbying the FDA to
revise its 2005 draft guidance on this issue, and the agency has indicated that it may do so in the near future. This updated
guidance will significantly shape the course of the personalized medicine marketplace, as it will further define the
regulatory requirements for more-targeted drugs and companion tests to gain FDA approval.
There are several pipeline drugs, especially in oncology, that are being developed with a companion diagnostic to better
identify the patients who will benefit from the drug. The following are two examples of this trend:
• Bapineuzumab is a pipeline biologic agent in development for Alzheimer’s disease. The drug’s efficacy appears to be
highest among patients who lack a specific genetic marker, the APOE-4 allele. A companion diagnostic test may be
required with this drug to determine the likelihood of response.
• Idebenone is a pipeline drug that is being developed for Friedreich’s ataxia, a rare genetic disorder that affects nervous,
cardiovascular, and endocrine systems. The condition is caused by the loss of the FXN gene on chromosome 9 and
occurs in 1 in 50,000 Caucasians. This genetic mutation can be used to identify the patients with the disease and more
specifically define the target population for this drug.
coverage policy trends
Debate continues regarding the incremental value provided by genomic testing and who will pay for the testing. In 2009,
CMS issued a recommendation that genetic testing for warfarin should be covered only in the context of a clinical trial
and should not be covered for routine clinical use, until evidence demonstrates more clearly the value of such testing.26 At
about the same time, the FDA revised the warfarin product label to include genetic testing information and, more recently,
dosing recommendations according to genotype.27 This apparent disconnect between government agencies contributes to
the confusion surrounding the role of genomic testing and personalized medicine. Similar debates are expected in 2010,
since CMS is currently evaluating cancer-related genomic tests and plans to issue a coverage recommendation by mid-year.
CMS policy will likely determine how these tests will be covered under federal plans, and it may also influence decisions by
commercial payers regarding the proper use of these tests.
45
Debate about personalized medicine will continue in the next few years as healthcare reform efforts continue to take shape.
A particular area of interest is how comparative effectiveness research (which attempts to identify the best treatment for
a particular condition) will align with the concepts of personalized medicine (which helps to identify the best treatment
for individual patients).28
The new technologies for personalized medicine have the potential to make clinical decision-making more precise,
leading to an overall improvement in healthcare. Plan sponsors can capitalize on this opportunity by providing coverage
for companion diagnostics and genetic tests when sufficient evidence shows that the tests can identify patients who will
respond to a treatment, or who are at increased risk for developing an illness and can take steps to prevent or delay its onset.
The key question is what represents adequate evidence, and this will be a topic of ongoing debate.
> Slow progress toward biosimilars (follow-on biologics)
Protein-based drugs or biologics, most of which are produced using recombinant DNA technologies, are playing an
increasingly important role in the treatment of many conditions. Since the first recombinant human insulin product
entered the market in 1982, over 100 different recombinant protein-based drugs have been approved. Another 633 biologics
and protein-based drugs are in various stages of clinical development.29 Biologic or protein-based drug therapies amounted
to about $76 billion in worldwide sales in 2008, and this number could grow to $115 billion by 2015, with sales increasing at
a much faster rate than for non–protein-based drugs.30 The lack of availability of lower-cost competitor versions is one of
the factors contributing to the rapid growth in spending for these drugs.
Creation of an approval pathway for biosimilar products is still under consideration, but progress appears to have been
slowed by the debate over national healthcare reform. Market forces may add to the pressure on regulators to develop a
new approval pathway. Recent announcements by several brand and generic pharmaceutical manufacturers suggest that
they are preparing to be active in developing biosimilar products. For example, Merck has created a new business unit called
Merck Bioventures, which aims to launch six or more follow-on biologics between 2012 and 2017.31
Once an approval pathway is enacted, it will take time for the FDA to work out the details of the process and for
manufacturers to prepare and submit their applications. Therefore, biosimilars are not likely to have a significant presence
in the marketplace for several years.
> Key therapeutic developments
Developments in the following therapeutic areas will be the primary determinants of drug trend over the next 3 years
(Figure 1):
• Central nervous system (CNS) drugs
• Endocrine and diabetes agents
• Musculoskeletal and rheumatological drugs
• Oncology drugs
• Respiratory agents
This is the first time since we have been creating these forecasts that oncology drugs have been among the top five trenddriving chapters. Cardiovascular drugs will continue to be one of the top categories of drug spending, but they are no longer
a leading driver of drug trend. Significant patent expirations have dramatically reduced the impact of cardiovascular drugs
as a trend driver, including the launch of generics for Zocor® (simvastatin) in 2006. This pattern will accelerate with the
introduction of generics for Lipitor® (atorvastatin) in late 2011.
Detailed forecasts of developments in these major therapeutic chapters are provided in the following pages.
46
> 2010
WHErE To FoCUS NEXT
WhErE to focus NExt
cardiovascular agents
Contribution to plan spending (2009): 20.4%
Projected contribution to trend (2010 to 2012): 7%
table 4.
drug trend projection for cardiovascular agents*
year
utilization increase
Annual total
2010
2011
2012
0% to 1%
1% to 2%
1% to 3%
0% to 1%
2% to 3%
2% to 4%
1% to 2%
0% to 1%
1% to 3%
*Projected change in drug spending on a plan ingredient-cost basis.
trENd prEdictioNs
key developments that are likely to shape drug trend in the cardiovascular chapter over the next 3 years:
• Increased use of combination drugs that reduce low-density lipoprotein (LDL) cholesterol and triglycerides,
and raise high-density lipoprotein (HDL) cholesterol
• Increased use of lipid-lowering therapy in primary prevention for patients with low/normal LDL, elevated
C-reactive protein (CRP), and other risk factors
• Two or more new oral anticoagulant drugs that will provide alternatives to warfarin treatment
• New antiplatelet drugs used alone or in combination with existing antiplatelet drugs
• Unit-cost savings resulting from new generics in the statin, angiotensin receptor blocker (ARB), and
antiplatelet therapy classes
trend drivers: New antiplatelet and anticoagulant drugs, new and existing cholesterol-lowering drugs
trend moderators: Increased availability of generic drug options to treat hypertension, high cholesterol, and
arterial thrombotic disorders
pipeline drugs: Some of the primary cardiovascular drugs in the pipeline are shown at the end of this
section (Table 5)
The cardiovascular chapter accounts for about 20% of plan spending and has historically been a significant contributor to
total trend. However, due to generic competition, this former trend driver will have a much lower impact than in the past.
Although significant progress has been made in managing cardiovascular disease in the United States, as evidenced by a
33% age-adjusted decline in mortality between 1990 and 2004, it remains a leading cause of death and disability.32
• Coronary heart disease (CHD) caused about 1 of every 6 deaths in the United States in 2006, with a total CHD mortality
of 425,000. In 2010, it is estimated that 785,000 Americans will have a heart attack, and about 470,000 will have a
recurrent coronary event. Thus, about every 25 seconds, an American will have a coronary event.33
• Each year, about 795,000 people experience a new or recurrent stroke. On average, every 40 seconds, someone in the
United States has a stroke.33
• Approximately one-third of adult Americans (about 81 million) have at least one type of cardiovascular disorder.
Among the most common types are hypertension (74 million), CHD (17.6 million), prior stroke (6.4 million), and heart
failure (5.8 million).33
47
The latest estimates also indicate that more than one-third of adults are obese and more than two-thirds are overweight.16
Excess body weight and obesity place people at risk for heart disease, stroke, diabetes, gallbladder disease, osteoarthritis,
and respiratory disease. The epidemic of obesity is also likely linked to the five-fold increase in triglyceride levels seen
during the past 30 years. About one-third of adults now have hypertriglyceridemia.34 Elevated triglyceride levels are also
a risk factor for CHD.
> Cholesterol management
Drugs used for cholesterol management have been the top spending category for most plans. However, the availability of
first-time generics in the statin category has dramatically changed this pattern. Plan ingredient-cost trend for cholesterollowering drugs is expected to be slightly negative during the first 2 of the next 3 years, and it will begin to decline more
sharply in 2012 due to the impact of new generics for Lipitor. At the same time, use of Crestor® for primary prevention in
patients with elevated highly sensitive C-reactive protein (CRP) and other cardiovascular risk factors is likely to increase,
counteracting some of the savings from existing and new generics.
Guidelines for cholesterol management
Results from the National Health and Nutritional Examination Survey (NHANES) indicate that self-reported use of statins
has increased from 8.0% to 13.4% during the period 1999 to 2006, an increase of 67% over this 8-year period.35 Also, during
the period 1988 to 2006, the use of statins by adults 45 years of age and older has increased about 10-fold, from 2% to 22%.36
While the prevalence of high LDL levels among patients age 20 years and older decreased from 31.5% in 1999-2000 to 21.2%
in 2005-2006, almost two-thirds of people at high risk for developing CHD within 10 years and who were eligible for lipidlowering drugs were still not receiving a medication.35 Clearly, LDL levels are heading in the right direction, but treatment of
people with high LDL who are candidates for cholesterol-lowering therapy is still falling short.35 Fortunately, with a generic
for Lipitor on the horizon, use of a generic statin will be a good option for almost all of the statin-eligible patients who are
not being treated.
C-reactive protein (CRP)
Results from the JUPITER trial could have a major impact on the use of cholesterol-lowering drugs over the next few years.37
In this trial, patients without high cholesterol but with elevated CRP levels received either Crestor® or placebo. CRP is a
marker for vascular inflammation and atherosclerotic plaque. In this study, Crestor significantly reduced the incidence of
major nonfatal cardiovascular events compared with placebo.
In February 2010, the FDA approved Crestor for reducing the risk of stroke, heart attack, and revascularization procedures in
patients 50 years of age or older with increased highly sensitive CRP and the presence of at least one additional cardiovascular
risk factor, such as hypertension, low HDL cholesterol, smoking, or a family history of premature CHD. This new indication
for primary prevention could translate into a patient population of almost 6 million new statin users, which would have a
significant impact on utilization of Crestor and cholesterol-lowering drugs in general. However, the increased use will likely
occur gradually, since changes to diet and exercise may also be an option for patients in this lower-risk population.
��
Treatment of mixed dyslipidemia
The prevalence of high LDL levels among people age 20 years and older was 21.2% in 2005-2006.35 Several million American
men and women also have low HDL values, a significant risk factor for serious cardiovascular events.38 The next crop of lipid
management therapies are aimed at treating mixed dyslipidemia—lowering LDL and triglyceride levels, while simultaneously
increasing HDL levels. Combination products containing simvastatin and niacin extended release or lovastatin and niacin
extended release are already available in the marketplace. However, these statin plus niacin combination products have not
made much of an impact on utilization in the cholesterol-lowering category. In general, utilization of fibrates, such as Tricor®
or Trilipix®, significantly exceeds the use of extended-release niacin in the cholesterol management marketplace. This may
be due to a higher level of intolerance for high-dose niacin regimens compared to fibrate therapy.
The next combination product to be introduced in this category will be a combination of Crestor and Trilipix. However, this
combination will simply allow patients to take one pill a day, instead of having to take the two products separately. Use
48
> 2010
of this combination product will also move market share away from Tricor or other generic forms of fenofibrate that are
currently more heavily utilized than Trilipix.
WhErE to focus NExt
research on niacin combinations
In 2009, the results of the ARBITER 6-HALTS study were released.39 This study showed that addition of extended-release
niacin to statin therapy resulted in significant regression of atherosclerotic plaque, as measured by carotid intima-media
thickness, whereas addition of ezetimibe to statin therapy did not have this effect. At this time, the majority of available
evidence appears to support use of niacin rather than ezetimibe or a fibrate as an add-on to statin therapy for halting
progression or even causing regression of atherosclerotic plaque. The results of this study and other studies that are in
progress will likely drive increased use of Niaspan® in combination with a statin in the coming years.
The National Heart, Lung and Blood Institute is also currently conducting a long-term outcome study (AIM-HIGH)
to determine whether raising HDL cholesterol with niacin therapy confers cardiovascular benefits. This multicenter,
randomized trial is designed to assess whether the combination of niacin plus simvastatin is superior to simvastatin alone
in delaying time to first major cardiovascular event over a 4-year follow-up period in patients with mixed atherogenic
dyslipidemia.40 Results of this study, which are expected in 2011, will help determine the ultimate place in therapy of niacinplus-statin combination products that lower LDL and raise HDL levels simultaneously.
other cholesterol-lowering and plaque-reducing drugs
Although the first cholesteryl ester transfer protein (CETP) inhibitor, torcetrapib, failed in clinical trials, research into this
novel class of drugs has not been halted, and two other CETP inhibitors, anacetrapib and dalcetrapib, are in Phase III trials.
These drugs can lower LDL while increasing HDL to an extent not possible with existing HDL-raising therapies. One or
both of these drugs may receive FDA approval as early as 2012. However, large outcome studies using hard cardiovascular
endpoints will be needed to prove the value of these drugs, and results of such studies are still years away.
In addition to new CETP inhibitors, a few novel cholesterol-lowering drugs are in the pipeline. Mipomersen, a novel antisense
compound directed against apolipoprotein B, a substance that is linked to elevated LDL cholesterol and development of
atherosclerotic plaque, has been shown to cause incremental reductions in LDL cholesterol and triglycerides when used
with a statin. Antisense drugs, like mipomersen, target and inactivate messenger RNA, thereby effectively suppressing the
activity of a gene that is producing a detrimental clinical effect.
In a recent Phase III trial, mipomersen added to maximally tolerated doses of a statin resulted in a 28% LDL reduction from
baseline levels, compared to a 5% reduction for the placebo group. This subcutaneously administered drug may be approved
in 2010 for use only in patients with very high cholesterol levels because of homozygous familial hypercholesterolemia.
Additional indications involving much larger populations of patients could come after 2011. As an injectable medication
used in a very limited population at a likely high cost, this drug may be included in the specialty category.
A second novel drug that specifically targets atherosclerotic plaque formation�darapladib�is in Phase III trials. Darapladib is
an orally active inhibitor of lipoprotein-associated phospholipase A2 (Lp-LPA-2), an enzyme linked to atherosclerotic plaque
formation. This drug is being studied in a 15,000-patient Phase III trial called STABILITY, which will enroll men and women
with existing CHD to determine if the drug will reduce the risk of death, heart attack, or stroke in this population. Results
of this trial are expected in 2012. Even if the results of this trial are positive, the drug will not likely be available until late
2012 or after.
impact of new generics
By the end of 2009, the three generic statins—lovastatin, pravastatin, and simvastatin—accounted for about two-thirds of
prescription market share among the pure statin drugs. These new generics will continue to moderate unit-cost growth as
the product mix shifts toward lower-cost options over the next few years. Near the end of 2011, the mega-blockbuster Lipitor
(atorvastatin) is also expected to lose patent protection. Based on current market share data, about 85% of pure statin
prescriptions could be dispensed using generics after this conversion occurs. The availability of generic statins is a major
factor in the relatively small contribution of the cardiovascular chapter to expected trend over the next 3 years.
49
> Antihypertensive drugs
Antihypertensives represent the largest single contributor to utilization in the cardiovascular category. Fortunately, this
category has become increasingly dominated by generic utilization over the past few years. Data from the latest NHANES
survey indicate that about 33% of U.S. adults over the age of 20—approximately 74.5 million adults—have high blood
pressure.33 Although about 68% of diagnosed patients are treated, hypertension is controlled to target goals in only 64%
of those who are treated.33 Efforts to ensure adherence to antihypertensive medications should help in the quest for more
effective control of high blood pressure.
High blood pressure is treated with several different types of drugs, including diuretics, beta-blockers, calcium channel
blockers, angiotensin converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs). These drugs are often
combined to help control blood pressure, and an increasing number of fixed-dose combination products including two and
even three classes of drugs are also becoming available.
First-time generics
Generic versions of Cozaar® (losartan) and Hyzaar® (losartan/hydrochlorothiazide) have been introduced this year—the
first drugs in the ARB class to become available in generic form. These two drugs account for about one-fifth of the
prescription market share in the combined ARB and ARB/diuretic category. The new generics create significant cost-saving
opportunities for plans, because ARBs have been the only remaining class of antihypertensive drugs that were available
only as single-source brands. Generics for at least two other drugs in this class, Diovan® and Atacand®, are likely to become
available during 2012, further reducing the need to prescribe a single-source brand in this class.
> Anticoagulant and antiplatelet drugs
Disease prevalence
The use of antiplatelet and anticoagulant drugs to prevent heart attack, stroke, and other vascular events continues to
grow rapidly. These two drug classes currently account for about 6% of overall drug trend. The populations eligible for
treatment with these medications are large and growing:
• According to the American Heart Association, 17.6 million Americans have CHD, 6.4 million have a history of stroke,
and about 8 million have peripheral artery disease.33 These conditions represent three large patient populations where
antiplatelet therapy may be indicated.
• In addition, venous thromboembolism—where a blood clot forms in a vein—affects about 300,000 Americans each
year, and about 2.7 million have either atrial fibrillation or atrial flutter.33 Oral anticoagulant therapy is often needed in
these two patient populations, as well as many other patient populations where there is an increased risk for venous
thromboembolism.
Introduction of new antiplatelet agents that may be an improvement over Plavix®, and new oral anticoagulants that do not
require the intensive monitoring needed for warfarin, could add significantly to growth in this category over the next few years.
Antiplatelet market evolution
Plavix (clopidogrel), the second largest-selling drug in the world, will lose patent protection in early 2012. However, the
focus in the antiplatelet category is now shifting to newer drugs that will provide alternatives for antiplatelet treatment.
Clopidogrel is a prodrug that needs to be converted to its active form to exert its effect. Patients who have genetic
polymorphisms in metabolizing enzymes and patients taking other medications, such as PPIs, may be unable or poorly
able to convert clopidogrel into the active compound.41, 42 Newer antiplatelet drugs do not appear to have the same issues,
so they may be preferred in patient populations where the efficacy of clopidogrel may be compromised. At the same time,
for the large population of patients who can convert clopidogrel efficiently into the active compound, clopidogrel (in brand
or generic form) may remain the preferred treatment. Pharmacogenomic testing can help identify the patients for whom
clopidogrel is the best treatment option and help ensure cost-effective treatment after the drug becomes available in
generic form.
New antiplatelet drugs
Effient® (prasugrel) was approved in 2009 for the reduction of thrombotic cardiovascular events (including stent
thrombosis) in patients with acute coronary syndrome who are to receive percutaneous coronary intervention. In a major
50
> 2010
WhErE to focus NExt
study, known as the TRITON TIMI 38 study, which compared prasugrel and clopidogrel in patients with acute coronary
syndrome who were scheduled for percutaneous coronary intervention, prasugrel therapy was associated with significantly
fewer ischemic events, including stent thrombosis, than clopidogrel.41 However, a small increased risk of bleeding, including
fatal bleeding, was reported with prasugrel. As a result, Effient has a black box warning for bleeding risk, and certain patient
populations, such as those with a prior stroke, should not be treated with prasugrel.
The next new antiplatelet drug to come to market is likely to be ticagrelor. The NDA for this drug was submitted in
November 2009. This drug has been compared to Plavix in a major study, known as the PLATO study, involving over 18,000
patients.43 In this study, ticagrelor outperformed clopidogrel in the reduction of vascular events, such as heart attacks and
stroke, and it was not associated with a higher rate of overall bleeding. The drug also reduced cardiac mortality, something
that was not seen in the study of prasugrel.
Ticagrelor is an active compound, and it is not influenced by the types of genetic variations or drug-drug interactions that
may impair the activity of clopidogrel. This drug also has a shorter duration of action than clopidogrel or prasugrel. This
would give it an advantage in situations where a patient needs to have cardiac surgery after a heart attack, and antiplatelet
therapy with a longer-acting drug would increase the surgical bleeding risk. The drawback is that ticagrelor needs to be
administered twice a day. Ticagrelor may be approved by the end of 2010, and could be a strong competitor and alternative
to clopidogrel in some circumstances.
A new antiplatelet agent, SCH 530348, with a unique mechanism of action—thrombin receptor inhibition—could also
come to market by 2011 or 2012. This drug targets the thrombin receptor on platelets, and preliminary evidence shows that
it further reduces vascular risk without any increase in bleeding risk when added to current therapy. Since this drug will
likely be an add-on antiplatelet therapy to be used with aspirin and clopidogrel, it could further increase cost and utilization
in the antiplatelet category once marketed.
New oral anticoagulants
Several novel oral anticoagulants are also in the near-term pipeline. Anticoagulants differ from antiplatelet drugs by
being used primarily to prevent blood clots in the veins, rather than in the arteries. These new agents could represent a
revolutionary change in oral anticoagulation therapy because they are used at a fixed dose and they do not require the
frequent coagulation monitoring required with warfarin, which has been the standard treatment for several decades. The
new drugs include several Factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban) and the reversible direct thrombin
inhibitor, dabigatran.
In March 2009, an FDA advisory board recommended approval of rivaroxaban for prevention of deep vein thrombosis
(DVT) following orthopedic surgery. In its complete response letter in May 2009, the FDA did not ask the manufacturer
for additional studies on this drug, but it did ask for additional long-term safety data. The manufacturer has indicated
that it will respond to the FDA later in 2010. Therefore, rivaroxaban could see an FDA approval for prevention of DVT
following orthopedic surgery by the beginning of 2011. Other indications, such as prevention of stroke in patients with atrial
fibrillation, and treatment of venous thrombosis and pulmonary embolism, could follow shortly thereafter.
FDA approval of dabigatran is also possible by the end of 2010 or early 2011. While an NDA has not yet been submitted in the
United States, the drug is already available in a number of other countries. Dabigatran has demonstrated efficacy similar to
that of Lovenox®, the standard of care for preventing DVT following orthopedic surgery. It has also been compared directly
with warfarin in several large clinical trials known by the acronyms RE-LY and RE-COVER.44, 45
The RE-LY study compared dabigatran to adjusted-dose warfarin for preventing stroke and systemic embolism in patients
with atrial fibrillation. In this study, dabigatran at doses of 110 mg twice a day or 150 mg twice a day was similar to or
better than adjusted-dose warfarin for reducing the rate of stroke and systemic embolism. The lower dose was associated
with a lower rate of hemorrhage compared to warfarin and the higher dose had a similar rate of hemorrhage compared
to warfarin.44 The RE-COVER study compared dabigatran at a dose of 150 mg twice daily to adjusted-dose warfarin for
preventing recurrent thromboembolism in patients with acute DVT.45 In this study, fixed-dose dabigatran was as effective
as adjusted-dose warfarin and had a similar safety profile.
51
Although more comparative studies of dabigatran and warfarin may be forthcoming, these two studies and the studies
comparing dabigatran with Lovenox provide significant support for dabigatran as a more convenient alternative to Lovenox
or adjusted-dose warfarin in a number of settings where there is an increased risk of clots and thromboembolism.
If these drugs gain approval for prevention or treatment of DVT and pulmonary embolism, prevention of stroke in patients
with atrial fibrillation, and treatment of acute coronary syndrome, they could become the standard of care for these
conditions and significantly increase both utilization and unit cost in the oral anticoagulant drug category. The new drugs
may provide safer alternatives to warfarin, and their use may be economically advantageous when considering both
medical and pharmacy costs.
New generics in the anticoagulant category
Generic versions of the injectable anticoagulant, Lovenox, are likely to become available by 2012, although approval
of a generic is possible during 2010.46 This drug is the standard of care for many circumstances where an injectable
anticoagulant is needed. Worldwide sales of Lovenox exceeded $4 billion in 2009, with U.S. sales accounting for a significant
portion.46 Lovenox is a complex mixture of large polysaccharide (sugar) molecules that will not be easy to replicate, and
the molecules may sometimes provoke an immune response, an effect known as antigenicity. Generic manufacturers
may need to demonstrate that their generic is no more likely to provoke an immune response than Lovenox. In addition,
generic substitution involving an injectable anticoagulant may be viewed with caution because of the risk of bleeding with
these drugs. In spite of these challenges, several companies have already submitted abbreviated new drug applications
(ANDAs) for this product, and these applications appear to be under consideration at the FDA. Approval of a therapeutically
equivalent generic for Lovenox would have a favorable impact on cost in this category, and it would help offset some of the
increased costs expected from introduction of new oral anticoagulants.
table 5. Some ambulatory-use cardiovascular agents in the pipeline
Generic name
Uses
2010
choline fenofibrate + rosuvastatin
dabigatran
Hypercholesterolemia/mixed dyslipidemia
Prevention and treatment of deep-vein thrombosis,
pulmonary embolism
Hypercholesterolemia/mixed dyslipidemia
pulmonary embolism
$
$$
pravastatin + fenofibrate
rivaroxaban
$
$$
2011
aliskiren + amlodipine
ticagrelor
Hypertension
Acute coronary syndrome
$
$
2012
anacetrapib
apixaban
High cholesterol/low high-density lipoprotein (HDL)
pulmonary embolism
Hypertension
High cholesterol/low HDL
Treatment/prevention of atherosclerosis
pulmonary embolism
Hypertriglyceridemia
Mixed dyslipidemia
High cholesterol
Acute coronary syndrome
Secondary prevention of stroke, myocardial infarction
Venous thrombosis
$$
$
azilsartan
dalcetrapib
darapladib
edoxaban
ethyl-eicosapentaenoic acid (AMR101)
laropiprant + niacin ER
mipomersen
otamixaban
SCH 530348 (TRA)
tecarfarin
$$ = potential to cause a > 2% increase in this category’s trend.
$ = potential to cause a < 2% increase in this category’s trend.
Bold text indicates potential specialty drugs.
52
Potential impact
on drug trend
Year
> 2010
$
$$
$$
$
$
$
$
$
$$
$
WHErE To FoCUS NEXT
WhErE to focus NExt
central nervous system (cNs) agents
table 6.
drug trend projection for cNs agents*
year
Annual total
2009
2010
2011
1% to 2%
2% to 3%
3% to 5%
2% to 3%
1% to 2%
3% to 5%
2% to 3%
4% to 5%
6% to 8%
*Projected change in drug spending on a plan ingredient-cost basis
trENd prEdictioNs
key developments that are likely to shape drug trend in the cNs chapter over the next 3 years:
• Conversion of the antiseizure category from a trend driver to a trend reducer due to many first-time generics
• Continued growth in utilization of antipsychotic medications used to treat schizophrenia, bipolar disorder,
and depression
• New drugs for the treatment of multiple sclerosis (MS), epilepsy, schizophrenia, depression, and Alzheimer’s disease
• New pain medications, including a new monoclonal antibody for pain, and reformulations of narcotic pain
relievers that may discourage abuse
• Continued growth in the attention deficit hyperactivity disorder (ADHD) category, and a new indication for
Nuvigil for symptoms associated with jet lag
• Many first-time generics, including generics for leading antidepressants, antipsychotics, and treatments for
Parkinson’s disease and Alzheimer’s disease
trend drivers: Narcotic pain relievers, atypical antipsychotics, drugs for ADHD, Cymbalta®, and new MS agents
trend moderators: Selective serotonin reuptake inhibitors (SSRIs), antiseizure medications, sleep agents,
migraine agents
pipeline drugs: Some of the primary CNS drugs in the pipeline are shown at the end of this section (Table 7)
The CNS chapter is a large and diverse group of drugs, representing about 23% of plan spending. This chapter consists of
many different classes of therapeutic agents, including drugs for pain, psychiatric illnesses, insomnia, Alzheimer’s disease,
MS, ADHD, migraine headache, Parkinson’s disease, and several other illnesses affecting the central nervous system.
> aNtisEizurE drugs
In recent years, utilization of antiseizure drugs has grown swiftly due to use of these drugs for nonseizure conditions such as
neuropathic pain, psychiatric conditions (e.g., bipolar disorder), migraine headache prevention, and restless leg syndrome.47
This trend is expected to continue, but costs will be substantially moderated by the introduction of many first-time generics
for highly utilized brand drugs in the category. Although several new antiseizure drugs are in development, spending in this
category is likely to be dominated by increased use of generics over the next few years, converting it from a trend driver to
a trend moderator.
53
New antiseizure medications
Several new antiseizure agents are expected to reach the market in the next 3 years:
• retigabine, a gamma-aminobutyric acid and potassium channel agonist, which has a unique mechanism of action
• eslicarbazepine, a once daily agent similar to oxcarbazepine (Trileptal®), but which may have less skin toxicity
• brivaracetam, a derivative of levetiracetam (Keppra®) which is now available as a generic
These drugs are being studied as add-on therapy for partial-onset seizures. However, the new drugs will be challenged to
distinguish themselves as substantially better than generically available alternatives. As with other agents in this category,
these new drugs may also be used for nonseizure indications.
First-time generics
Unit costs for antiseizure agents have been significantly reduced by the introduction of many generics in this category. Firsttime generics for Depakote® ER (divalproex extended release), Topamax® (topiramate), and Tegretol® XR (carbamazepine
extended release) were all approved in 2009. Combined with the multiple first-time generics in the category during 2008,
the new generics have resulted in a dramatic and favorable change in unit costs. No new generic antiseizure drugs are
expected until 2012, when patents expire on Gabitril® (tiagibine). Sales of Gabitril were $54.9 million in 2009.13
> Antidepressants
Utilization of antidepressants is likely to grow slowly over the next 3 years. Although serotonin-norepinephrine reuptake
inhibitors (SNRIs) lack clear evidence of superiority over other antidepressants, they are likely to generate most of the
growth in the category.48 Growth is also expected to result from treatment of patients with fibromyalgia syndrome (FMS),
a chronic pain syndrome often accompanied by depression. FMS affects approximately 1% to 5% of the U.S. population.49
Continued use of SNRIs, particularly Cymbalta®, for FMS and potential future indications, such as chronic lower back and
osteoarthritis pain, may fuel utilization growth in this category. Back pain affects up to 14% of Americans, and approval of
this new indication could expand the population of users and make this drug a major competitor in the pain management
marketplace.50
Vilazodone is the only new antidepressant in the near-term pipeline with approval possible in 2011. Vilazodone is an SSRIlike antidepressant that was being developed with a companion diagnostic. However, confirmatory studies did not validate
the biomarker and the manufacturer has submitted the drug to the FDA without the biomarker information.51
Generic antidepressants
Unit-cost growth among antidepressants is expected to be moderated by savings in the SSRI category. Utilization of
SSRIs is likely to remain flat, but unit cost is likely to decline because the SSRI category is now predominantly generic, and
Lexapro® (escitalopram), the last remaining branded SSRI, is expected to lose patent protection in 2012. Additionally, firsttime generics for Effexor XR® (venlafaxine extended release), an SNRI that accounted for approximately $2.6 billion in drug
spending in 2009, may reach the market by mid 2010.13 The availability of generics for these two blockbusters will likely
lead to a negative cost trend in this category.
> Atypical antipsychotics
Atypical antipsychotics have almost entirely replaced traditional agents. The category currently accounts for about 6% of
overall trend and is expected to show high single-digit increases in growth over the next 3 years. In addition to being used
to treat schizophrenia, many of these drugs are also approved for short- and long-term treatment of mania associated
with bipolar disorder. Off-label uses for these drugs include obsessive-compulsive disorder, post-traumatic stress disorder,
personality disorders, and dementia.
New atypical antipsychotics
Lurasidone is a new atypical antipsychotic being developed for the treatment of schizophrenia. In pivotal trials, lurasidone
demonstrated significantly greater improvements on the Positive and Negative Syndrome Scale compared with placebo.
Additionally, lurasidone had effects on body weight that were similar to placebo. Lurasidone was submitted to the FDA
in early 2010 and could reach the market in 2011.52 A new inhaled formulation of loxapine is also in development that will
deliver this conventional (typical) antipsychotic via an inhaler for the treatment of acute episodes of agitation associated
54
> 2010
with schizophrenia. If approved, this would be the first formulation of an antipsychotic designed for inhalation delivery. A
loxapine inhaler could reach the market in 2011.53
WhErE to focus NExt
first-time generics
Generics for Risperdal® (risperidone) have already provided a useful option in this formerly all-branded category of drugs.
Additional first-time generics for Zyprexa (expected in 2011), Seroquel (expected 2012), and Geodon (expected late 2012)
are likely to have a significant impact on costs in this category in the next few years. Together these three products were
responsible for $6.4 billion in U.S. sales in 2009.13 The availability of at least four generic options in this category by the end
of 2012 could help change this category from a trend driver to a significant trend moderator by 2013. However, the tendency
to treat this class of drugs as “protected” and not suitable for step therapy may prevent potential savings opportunities.
> MultiplE sclErosis (Ms)
Drugs used to treat MS are second only to rheumatological drugs as a main driver of specialty drug spending. Utilization of
these drugs is likely to grow in the next few years as manufacturers race to develop the first oral disease-modifying agent
for this illness. Several of these new drugs may reach the market in the next 3 years. The current therapy for MS includes
injectable medications such as beta-interferons, which are sometimes poorly tolerated, and Copaxone®. Oral agents
could help improve patient adherence, and new mechanisms of action may provide some incremental benefit in terms of
reducing disease exacerbations.
Dalfampridine (Ampyra™), an oral drug that blocks potassium channels in nerves, was approved by the FDA in January 2010
to improve walking speed in patients with MS. This drug will be used in all forms of MS, not just the relapsing-remitting form
of the disease. However, studies indicate that the drug provides only a modest average benefit in improving walking speed,
and the drug does not have a long-term effect in decreasing disease exacerbations or delaying the progression of disability
from the disease.54 This drug will be used in addition to current immunomodulating drugs as part of the treatment of MS.
pipeline drugs
Several additional oral drugs for treatment of MS are expected to reach the market in the next 3 years. These agents
are being studied as monotherapy for relapsing-remitting MS. If approved, these agents could be used in place of betainterferons and would likely be priced similarly to interferons.
Fingolimod is a once-daily oral immunosuppressant that lowers the levels of activated T-cells in the bloodstream and in the
CNS. If approved, fingolimod would be the first in a new class of drugs called S1P receptor modulators. Recently published
data indicate that the drug may have better efficacy (significantly fewer relapses) compared with interferon beta-1a.55
Fingolimod could reach the market by the end of 2010.
Cladribine is a chemotherapeutic agent that impairs DNA repair and interferes with the proliferation of white blood cells
that accompany MS.56 Cladribine has been used off-label as a treatment for MS, but currently it must be given by intravenous
or subcutaneous injection. An oral formulation of cladribine is being developed specifically for MS and is expected in 2011.
When studied against placebo, oral cladribine resulted in fewer relapses, delayed progression of disability, and fewer lesions
detected using MRI.57 Oral cladribine can cause lymphocytopenia, but has the advantage of cyclical administration in several
short cycles a few times a year.
BG-12, dimethyl fumarate, is an immunomodulator that has a mechanism different from currently available agents. It is
being studied as initial monotherapy for relapsing-remitting MS, but its complementary mechanism may lead to its use
as an add-on agent, especially since it has not yet demonstrated the same level of efficacy as other pipeline agents, like
fingolimod or oral cladribine. BG-12 is expected to reach the market in 2011.56
Laquinamod is an oral immunomodulator that reduces inflammatory activity in MS. When studied in patients with
relapsing-remitting MS, treatment with daily doses of laquinamod resulted in significant reductions in gadoliniumenhanced lesions identified on MRI when compared to placebo.58 Although it appears to have modest efficacy in relapsingremitting MS, it has the benefit of once-daily administration along with a favorable side effect profile. Laquinamod has
been granted fast track status by the FDA and could reach the market by late 2011 or in 2012.56
55
These new oral agents will join the other specialty drugs currently used for the treatment of MS, leading to increased costs
in the category. However, these new drugs may be challenged to displace existing therapies that already have favorable
long-term safety and efficacy profiles.
> NoNNarcotic paiN rEliEvErs
Naproxcinod, a novel form of naproxen that releases nitric oxide, may have protective effects on the gastrointestinal
tract and may protect against NSAID-induced ulcers. The new drug, which is likely to be introduced in 2010, provides pain
relief similar to naproxen in patients with osteoarthritis.52 Moderate utilization growth for the nonnarcotic analgesics will
probably continue over the next 3 years, tempered by unit-cost savings from the large number of generics in the class.
> Narcotic paiN rEliEvErs
Utilization of narcotic pain relievers is likely to increase by about 9% per year over the next 3 years, due in part to the
introduction of new formulations of narcotics that offer reduced potential for abuse or improved dosing convenience.
OxyContin® (oxycodone) is the market share leader in the narcotic category, responsible for over $3 billion in drug
expenditures in 2009.13 Generic versions of OxyContin were available for a brief period in 2008, but they were withdrawn
from the market when the brand manufacturer won a patent lawsuit. Generics for OxyContin are not expected to re-enter
the market until the patent expires in 2013. A new abuse-resistant formulation of OxyContin may extend the patent life of
this product even further, but the potential for reduced abuse is not yet well-documented.52
A new once-daily form of hydromorphone, Exalgo®, was approved in March 2010. This product will provide another option
for long-term pain relief, competing with OxyContin.
abuse-resistant narcotic formulations
Products in the pipeline include several reformulations of currently available narcotics that are designed to have a lower
risk for abuse or misuse. The first such product was approved in 2009. Embeda™ contains morphine sulfate and naltrexone
(a morphine antagonist); crushing or otherwise destroying the tablets releases naltrexone, blocking the effects of the
morphine. Remoxy® is a pipeline extended-release version of oxycodone formulated as a gel cap that has shown resistance
to dissolution with alcohol and cannot be crushed. Acurox® contains oxycodone and subtherapeutic amounts of niacin;
if the product is destroyed by crushing it or otherwise tampering with it, the niacin is released and produces unpleasant
adverse effects such as flushing, headache, and itching. Finally, Oxytrex™, anticipated in 2010, is a new formulation of
oxycodone that contains ultra-low doses of naltrexone, which is included to reduce development of tolerance to the effects
of oxycodone.
a completely new treatment for chronic pain
By 2012, the pain management field could see introduction of a completely new treatment for pain. The new drug is
tanezumab, a monoclonal antibody directed at blocking the effects of nerve growth factor, which plays a role in pain
transmission. This drug represents a completely new way to treat pain and it will be the first monoclonal antibody ever used
for this indication. This drug is administered by intravenous infusion once every 1 or 2 months. It is being studied for relief
of pain due to osteoarthritis, chronic lower back problems, and interstitial cystitis. These types of pain are currently treated
with NSAIDs, such as naproxen, or narcotic analgesics.
Tanezumab, a monoclonal antibody, will join the ever-expanding category of high-cost specialty drugs. As such, use of this
drug will probably need to be reserved for when other treatments have failed or cannot be used.
first-time generic
The only new generic long-acting narcotic analgesic on the horizon is a generic version of Kadian® (morphine extended
release), which may lose patent protection in 2010. Kadian sales were $294 million in 2009.13
56
> 2010
> alzhEiMEr’s disEasE
WhErE to focus NExt
Utilization of drugs for Alzheimer’s disease continues to grow at a rate of about 6% per year. Several diseasemodifying pipeline drugs have recently been discontinued because of disappointing efficacy results. However, one drug—
bapineuzumab, a monoclonal antibody targeted against beta-amyloid—has shown promise, especially in patients without
a specific genetic marker (APOE4-negative patients). Bapineuzumab could reach the market in 2012, perhaps with use
limited to the population of patients without APOE4.
Another drug for Alzheimer’s disease, latrepirdine, is a small-molecule drug that has been marketed in Russia for some
time as an antihistamine. It has recently been found to have properties that may be useful in the treatment of Alzheimer’s
disease. When studied in patients with mild to moderate Alzheimer’s disease, the drug has demonstrated improvements in
cognition in early studies, whereas those treated with placebo demonstrated deterioration in cognitive function.59 Recent
Phase III trials have not confirmed these findings and the future of latrepirdine is in doubt.
First-time generics for Aricept (donepezil) could be introduced sometime during 2010. Generic versions of Aricept could
result in substantial savings for plans; the drug accounted for approximately $1.4 billion in U.S. sales in 2009 and is the most
widely used treatment for the condition.13 However, a long-acting, higher dose version of Aricept is also in development, and
this product could reduce the impact of first-time generics for Aricept. This new version of Aricept will need to be evaluated
carefully to determine whether it provides some measurable advantage over the new generic.
> sEdativE-hypNotics
Almorexant is the only new sedative-hypnotic drug expected in the next few years. In the first pivotal trial, almorexant
demonstrated significant improvements in sleep maintenance compared to placebo.52 If additional studies demonstrate
similar efficacy, and if safety concerns exposed during the first trial are adequately addressed, almorexant could reach the
market in 2011.
Generics for Lunesta® (eszopiclone) are expected to reach the market in mid 2012. With generic zolpidem (Ambien®) already
available, this is another category that could be almost all generic in utilization by the end of 2012.
> cNs stiMulaNts
CNS stimulants and drugs used to treat attention deficit hyperactivity disorder (ADHD) were a significant trend driver
in 2009, and this pattern of rapid growth is expected to continue in the next 3 years. This category includes drugs like
Adderall XR®, Concerta®, Vyvanse®, Provigil®, and Nuvigil®.
One of the trend-driving drugs in the category, Nuvigil (armodafinil), the single isomer version of Provigil (modafinil), could
win a new indication in 2010 for the treatment of sleepiness associated with jet lag. In a recent trial, armodafinil was given
to travelers after a flight eastward across six time zones. Armodafinil resulted in reductions in self-rated daytime sleepiness,
an increase in alertness, and decreases in the time needed to fall asleep. If armodafinil is approved for jet lag, plans will need
to determine whether jet lag is a covered use and in what quantities the drug should be provided per month. Treatment
is likely to require only a few tablets per trip, but this use could involve a sizeable population.60, 61 In March 2010, the FDA
declined to approve this indication; however, the manufacturer may still pursue development of the drug for this use.
First-time generics for Provigil are likely to enter the market in 2012. Combined annual sales of Provigil and Nuvigil are
currently almost $1 billion.13 Since Nuvigil is a single-isomer version of Provigil, the new generic is likely to displace both
brands in the marketplace in 2012, resulting in substantial savings to plans.
57
table 7. Some ambulatory-use CNS agents in the pipeline
Generic name
Uses
2010
ketorolac intranasal
fingolimod
naproxcinod
safinamide
ibuprofen + famotidine
naproxen + esomeprazole
eslicarbazepine
oxycodone extended release
(abuse-resistant formulation)
oxycodone + niacin
retigabine
idebenone
Pain
Multiple sclerosis
Osteoarthritis
Parkinson’s disease
Mild-to-moderate pain
Pain
Seizure disorders
Chronic pain
$
$
$$
$
$
$
$
$
Chronic pain
Seizure disorders
Friedreich’s ataxia
$
$
$
2011
loxapine inhalation
lurasidone
vilazodone
BG-12 (dimethyl fumarate)
cladribine (oral)
esmirtazapine
almorexant
morphine + oxycodone
Acute agitation in schizophrenia
Schizophrenia
Depression
Multiple sclerosis
Multiple sclerosis
Insomnia, hot flushes
Insomnia
Pain
$
$
$
$
$
$
$
$
2012
brivaracetam
laquinamod
pardoprunox
bapineuzumab
latrepirdine
tanezumab
Seizure disorders
Multiple sclerosis
Parkinson’s disease
Pain associated with osteoarthritis
$
$
$
$$
$
$$
58
Potential impact
on drug trend
Year
> 2010
WHErE To FoCUS NEXT
WhErE to focus NExt
Endocrine and diabetes agents
table 8.
drug trend projection for endocrine and diabetes agents*
year
Annual total
2010
2011
2012
1% to 2%
8% to 9%
9% to 11%
1% to 2%
8% to 9%
9% to 11%
1% to 2%
9% to 10%
10% to 12%
trENd prEdictioNs
key developments that are likely to shape drug trend in the endocrine and diabetes chapter over the next 3 years:
• Continued rapid growth in utilization of diabetes drugs due to the epidemics of obesity and diabetes in this country
• Increased use of multiple-drug therapy to help control blood glucose levels and prevent long-term
complications of diabetes
• Introduction of several new oral and injectable agents for the treatment of diabetes and its complications
• A new drug to prevent or delay the onset of type 1 diabetes
trend drivers: New users of oral and injectable hypoglycemic agents, including modified insulin products such
as Lantus® and Humalog®
trend moderator: None, as first-time generic for Actos® has been delayed until 2012
pipeline drugs: Some of the primary endocrine and diabetes drugs in the pipeline are shown at the end of this
section (Table 9)
> diaBEtEs
There are two forms of diabetes, type 1 and type 2. Type 1 diabetes is usually diagnosed in children and young adults, and
was previously known as juvenile diabetes. In type 1 diabetes, the body does not produce enough insulin. Only 5% of people
with diabetes have this form of the disease. Type 2 diabetes is the most common form of diabetes. In type 2 diabetes,
either the body does not produce enough insulin or the cells ignore the insulin that is produced. Patients with diabetes
are at significantly increased risk for cardiovascular, kidney, and eye diseases. In addition to managing blood glucose levels,
patients with diabetes need to manage cholesterol, blood pressure, and other risk factors.
obesity and diabetes
The epidemic of diabetes continues to evolve at an unprecedented rate. Recently, the CDC estimated that the incidence of
diabetes in the United States has more than doubled in the last 15 years.62 In addition, the American Association of Clinical
Endocrinologists (AACE) estimated that there are 24 million Americans with diabetes, and each year, 1.3 million people are
newly diagnosed with type 2 diabetes.63 Also, the CDC estimates that another 57 million Americans have prediabetes, a
condition characterized by elevated fasting glucose levels, placing them at high risk for developing type 2 diabetes.64
59
The combined population of people with diabetes and prediabetes represents an enormous future burden on our already
strained healthcare system. Dietary modifications and regular exercise might delay or prevent the development of diabetes
in many people with prediabetes, but these lifestyle changes are difficult to follow consistently over a long period of time.
As a result, obesity-related onset of diabetes is likely to be a major contributor to the rapid utilization growth of diabetes
drugs over the next several years.
In spite of the availability of numerous drugs to help treat diabetes and related disorders, only a fraction of patients with
the disease achieve their target goals for blood glucose, cholesterol, and blood pressure. The remaining patients represent
an undertreated population that will accelerate future utilization growth for diabetes and cardiovascular drugs, and drugs
used to treat or prevent other conditions that affect patients with diabetes.
New FDA guidance for drug approvals
Several new pipeline drugs for the treatment of type 2 diabetes may be approved over the next several years. However, the
timing of these approvals hinges on how the FDA applies its recent guidance for evaluating new diabetes treatments. The
new guidelines require manufacturers to evaluate the cardiovascular risk associated with a new diabetes drug, as well as the
drug’s ability to control blood glucose.65 The new FDA guidance significantly increases the number of patients who must be
exposed to a drug during clinical development, and it also requires inclusion of high-cardiovascular-risk patients in clinical
trials. Consequently, there could be delays in FDA approval of some diabetes medications that are already in the pipeline.
New injectables
Glucagon-like peptide-1 agonists (GLP-1), a new class of injectable treatments, have multiple effects on blood glucose
control. They stimulate the secretion of insulin in the presence of elevated blood glucose, slow gastric emptying, and inhibit
secretion of glucagon. Over time, the use of these drugs often leads to weight loss—an unusual benefit among drugs for
diabetes.
A new injectable agent, liraglutide (Victoza®), was approved at the beginning of 2010 for the treatment of type 2 diabetes.
Liraglutide acts similarly to Byetta® (exenatide) in reducing A1C levels and weight, and is administered only once daily.
However, liraglutide has been linked to an increased risk for thyroid cancer in animals. Whether this risk also exists for
humans is unclear. Thus, this drug is not recommended as a first-line agent.
A new dosage form of exenatide, called exenatide LAR, is also under FDA review and could be on the market in the second
half of 2010. Administered by once-weekly injection, the new dosage form would be an advance in terms of convenience
and long-term glucose control, and it may set a new standard for medications to treat diabetes. Other injectable GLP-1
agonists also under clinical development include lixisenatide and taspoglutide. Either or both of these drugs could be
approved in the next few years.
New oral drugs
Saxagliptin (Onglyza®), a new oral dipeptidyl peptidase IV (DPP-IV) inhibitor, was approved during the second half of 2009.
Several additional oral DPP-IV inhibitors and DPP-IV combination products are in late-stage clinical development, including
alogliptin, saxagliptin/metformin, vildagliptin, and vildagliptin/metformin. These drugs are likely to be used as part of
multiple-drug combinations for patients with diabetes.
Sodium-glucose transporter-2 inhibitors
A new area of diabetes drug development involves agents that prevent reabsorption of glucose in the kidneys. These drugs
help lower blood glucose levels by blocking a molecule that transports glucose from the urine back into the body, and they
may also play a role in the absorption of glucose from the small intestine. Dapagliflozin, currently in Phase III development,
may be the first drug in this new class to be approved during the next 3 years.
60
> 2010
WhErE to focus NExt
New treatment for type 1 diabetes
Type 1 diabetes is an autoimmune disorder in which the immune system attacks the patient’s pancreas, making it unable to
secrete insulin. These patients require lifelong treatment with insulin injections. While the search for pump technology that
can essentially provide an artificial pancreas continues, multiple daily insulin injections or continuous infusion of insulin via
a pump remains the mainstay of therapy for type 1 diabetes.
Scientists have shown that suppressing the immune system can prevent or delay type 1 diabetes in animals. As a result of
this research, several monoclonal antibodies to delay the onset of type 1 diabetes are under clinical development in humans.
These drugs are designed to prevent immune cells, known as T-cells, from attacking and destroying the insulin-producing
cells in the pancreas. Current data indicate that these agents can delay the use of insulin and preserve pancreatic function
for up to 1 year.
Otelixizumab is the first such treatment that may be approved in the next 3 years to delay the onset of type 1 diabetes. This
drug would be used to help preserve pancreatic beta cell function in patients who are newly diagnosed with type 1 diabetes.
The drug is likely to be the first specialty drug in the diabetes category.
Biosimilars for insulin
Modified insulins, such as Lantus®, Humalog®, and Novolog®, are the primary trend drivers in the diabetes class, which
accounted for a remarkable 17% of trend in 2009. These insulins are small-molecule proteins that should be relatively easy
to replicate once the patents expire by 2015. However, a pathway for follow-on biologics will need to be developed before
alternative versions of these drugs can be marketed.
table 9.
some ambulatory-use endocrine and diabetes agents in the pipeline
potential impact
on drug trend
year
generic name
uses
2010
exenatide long-acting formulation
Type 2 diabetes
$
2011
valsartan + nateglinide
$$
lixisenatide
inhaled insulin
reduction in risk for newonset type 2 diabetes
Type 2 diabetes
Type 2 diabetes
alogliptin
otelixizumab
dapagliflozin
taspoglutide
Type 2 diabetes
Delay onset of type 1 diabetes
Type 2 diabetes
Type 2 diabetes
$
$
$
$
2012
$
$
61
WHERE TO FOCUS NEXT
Musculoskeletal and rheumatological agents
table 10.
Drug trend projection for musculoskeletal and rheumatological agents*
Year
Annual total
2010
2011
2012
1% to 2%
6% to 7%
7% to 9%
1% to 2%
12% to 13%
13% to 15%
1% to 2%
12% to 13%
13% to 15%
Trend predictions
Key developments that are likely to shape drug trend in the musculoskeletal and rheumatological chapter over
the next 3 years:
• Introduction of denosumab, initially for the treatment of osteoporosis, with several additional indications
likely to follow
• Use of the interleukin-6 antagonist tocilizumab as a new treatment strategy for rheumatoid arthritis (RA)
• Increased use of existing biologics for the treatment of RA
• Introduction of a novel high-cost injectable biologic agent for treatment of refractory gout, and increased
use of Uloric® as a replacement for allopurinol
• Introduction of one or more new injectable biologics for the treatment of systemic lupus erythematosus
(SLE) and lupus nephritis (LN)
Trend drivers: Increased use of existing biologics for RA, and new high-cost drugs for the treatment of
osteoporosis, gout, SLE, and LN
Trend moderator: Nothing significant, since the generic versions of Fosamax® have already reduced costs in the
category, and the impact of generics for Fosamax with D is likely to be small
Pipeline drugs: Some of the primary musculoskeletal and rheumatological drugs in the pipeline are shown at
the end of this section (Table 11)
> Osteoporosis
An estimated 44 million Americans have been diagnosed with osteoporosis or are at risk of developing the condition.66
Plan spending for this treatment class has generally declined in 2009, due to the introduction of generics for Fosamax®
(alendronate). However, the impact of these generics will diminish, and spending will increase once again with the likely
introduction of denosumab in late 2010. Denosumab is a twice-yearly, subcutaneously administered biologic that is likely
to be high in cost.
Setbacks for new SERMs
Selective estrogen receptor modulators (SERMs) are drugs that have estrogen-like beneficial effects on bone and lipid
profiles, but antagonize estrogen’s effects on reproductive tissues, such as those of the breast and uterus. Evista® was
the first SERM to win FDA approval, and it is now also approved for use in reducing the risk of invasive breast cancer in
postmenopausal women with osteoporosis or women at increased risk for breast cancer.
62
> 2010
WhErE to focus NExt
In September 2008, an FDA advisory board recommended approval of a second SERM, lasofoxifene, for the treatment
of osteoporosis in certain postmenopausal women who are at high risk and cannot tolerate other therapies. The FDA
requested additional information on the drug in January 2009. Although lasofoxifene has been approved in Europe for
treatment of osteoporosis in postmenopausal women at increased risk of fracture, no progress has been reported on FDA
approval of the drug. If approved and marketed, the impact of the new drug in the osteoporosis market is expected to be
modest, because SERMs are generally less favored than bisphosphonates for treating or preventing osteoporosis.
Another pipeline SERM, bazedoxifene, may be approved in 2010. However, bazedoxifene has already received two
approvable letters from the FDA, and concerns about a possible increased risk of stroke and thromboembolism appear to
have contributed to a delay for this drug. A combination product containing bazedoxifene and conjugated estrogens could
be approved in 2011. This combination may help minimize endometrial thickening caused by conjugated estrogen, while
alleviating postmenopausal symptoms that might be worsened by bazedoxifene alone.
A third new SERM, arzoxifene, a compound closely related to Evista, appears to have been dropped from further clinical
development after the compound failed to demonstrate a reduction in nonvertebral fractures in a large Phase III trial. The
drug was also associated with an increased risk of venous thromboembolism, leg cramps, and hot flushes compared to
placebo.67 At this time, there do not appear to be any other SERM products in the near-term pipeline.
a new biologic for osteoporosis
A new monoclonal antibody for the treatment of osteoporosis, denosumab, may be introduced later in 2010. Denosumab
inhibits the activity of osteoclasts, the cells responsible for breakdown of bone, by inhibiting the activation of the nuclear
factor kappa B pathway. Published data suggest that denosumab may equal or surpass Fosamax in increasing bone mineral
density (BMD).68 Denosumab also appears to be effective in increasing BMD in patients with breast cancer who are being
treated with antiestrogen agents, and patients with prostate cancer receiving antiandrogen drugs; both of these therapies
are known to accelerate bone loss and increase fracture risk.69, 70 However, the FDA is not likely to approve this use until
additional studies provide evidence for the safety of this drug in patients with cancer.
An FDA advisory board has recommended approval of denosumab for the treatment of postmenopausal osteoporosis and
the treatment of bone loss in patients undergoing hormone ablation for prostate cancer. The FDA may initially approve this
drug only for the treatment of postmenopausal osteoporosis, and it is likely to require a REMS program to help manage the
potential cancer and infection risks associated with the drug. The agency may require additional studies before approving
the drug for prevention of postmenopausal osteoporosis and for patients with existing cancer, because of the possible
increased risk of cancer and infections with the drug.
The manufacturer of denosumab is also seeking an indication for this drug to reduce the risk of further skeletal events, such
as fractures and spinal cord compression, in patients with breast cancer, prostate cancer, other solid tumors, and multiple
myeloma who already have bony metastasis. Invasion of the bone by the cancer is a very common problem in these cancers.
Approval of denosumab for these indications would allow it to compete directly with zoledronic acid (Zometa®), which is
the standard treatment for this condition.
Denosumab is also being studied for reducing the risk of first bony metastasis in patients with metastatic prostate cancer
that has not yet infiltrated the bone. This use represents a significant market opportunity for denosumab, and one in which
there are currently no other FDA-approved products, including Zometa. In the case of this use, the dosing for denosumab
may be as high as 120 mg monthly instead of the 60 mg twice-yearly dose used for treating osteoporosis. Thus, this use of
denosumab will be much more costly than the use for osteoporosis.
other drugs for osteoporosis
Odanacatib, a new drug for the treatment of osteoporosis, is being studied in Phase III trials for the treatment and
prevention of osteoporosis and for the reduction of skeletal events in women with breast cancer and bone metastasis.
This is the first drug to inhibit cathepsin K, which is found on osteoclasts, the cells involved in the breakdown of bone.
It is too early to judge how odanacatib will perform relative to bisphosphonates. It will probably not be introduced until
late 2012 or 2013.
63
> Rheumatoid arthritis (RA)
Treatment trends
RA is a common condition affecting more than 2 million Americans, many of whom are candidates for treatment with
an existing biologic agent. These agents, which are often used in combination with methotrexate, can achieve disease
remission and stop joint erosions to an extent not previously possible. In 2009, this category of drugs was second only to
drugs for multiple sclerosis as a trend driver in the specialty category.
A wide variety of biologics are now available to treat RA and other immune-mediated disorders, including:
• Five tumor necrosis factor (TNF) inhibitors that are approved for first-line use alone or in combination with
methotrexate: Enbrel®, Humira®, Remicade®, Simponi®, and Cimzia®
• Rituxan, a second-line agent that treats RA by targeting and destroying B-lymphocytes
• Actrema, a second-line therapy that acts as an interleukin-6-receptor antagonist
• Orencia, a first-line therapy that acts by reducing T-cell activation
Biologics are being used much earlier and more frequently in RA treatment, as results from clinical trials continue to
demonstrate their excellent efficacy and safety profiles. The American College of Rheumatology recommends the use of
TNF inhibitors to treat newly diagnosed RA in patients with high disease activity or those with longer-duration RA who
have had an inadequate response to methotrexate. For patients who do not respond to TNF inhibitors, Orencia, Rituxan,
and Actrema® are other options.
New specialty drugs for RA
Ocrelizumab, a second generation, fully humanized anti-CD-20 monoclonal antibody was studied in Phase III trials for
treatment of RA in combination with methotrexate. As with Rituxan, depletion of B-cells with ocrelizumab reduces the
signs and symptoms of RA and may also reduce the joint space narrowing and erosions associated with this condition.
However, Roche announced in March 2010 that development of ocrelizumab for RA has been suspended due to adverse
events, including deaths, in patients treated with this drug.
A second pipeline drug, CP-690550, is an oral, small-molecule, immunosuppressive agent that acts as an inhibitor of the
Janus-activated kinase type 3 (JAK3) enzyme. The JAK3 enzyme plays a role in lymphocyte proliferation, differentiation,
and survival, so a JAK3 inhibitor could be useful for the treatment of RA. Phase III trials of CP-690550 for treating RA were
started in April 2009, so this drug is not likely to be approved until 2012 or later. An effective and safe oral drug would make
treatment of RA more convenient for patients.
> Gout
Gout is a form of arthritis that affects mostly men. The symptoms are caused by the collection of urate crystals in the joints,
which is very painful and can lead to joint destruction. The lifetime prevalence of gout is approximately 2.6% for adults age
20 and older; in 2005, an estimated 6.1 million adult Americans had gout.71 Allopurinol, which decreases uric acid production,
has been used for decades to prevent gout. About 12 million prescriptions were written for allopurinol in the United States
during 2009.13
For patients with gout for whom other drug treatments have failed, a new biologic agent is also on the horizon. Pegloticase
is an intravenously administered recombinant enzyme (urate oxidase or uricase) that breaks down uric acid into a harmless
substance that can be easily eliminated. The enzyme is pegylated to prolong its duration of action and allow administration
every 2 to 4 weeks. It appears to dissolve urate crystals in the joints much more quickly than currently available drug
treatments, giving it a possible advantage over existing drugs in selected patients.
Approval of pegloticase for the treatment of refractory gout is possible by the end of 2010, and the new drug will likely
include a REMS program. The drug has been associated with serious infusion reactions and possibly an increased risk of
cardiovascular adverse events, so it will need to be monitored closely. Introduction of pegloticase will move treatment of
refractory gout into the high-cost specialty arena, and could contribute to rising costs in a therapeutic area that has long
been dominated by generics.
64
> 2010
> systEMic lupus ErythEMatosus (slE)
WhErE to focus NExt
SLE is a chronic relapsing and remitting autoimmune disorder that affects mostly women. The disease, which currently
has no cure and is associated with frequent flares, causes damage to a variety of body organs, including skin, heart,
joints, blood vessels, and kidneys. Current treatments, which are aimed at reducing disease flares, include a variety of
immunosuppressive drugs that are used off-label, such as prednisone, azathioprine, methotrexate, mycophenolate, and
antimalarials, such as hydroxychloroquine. No new drugs for this disorder have been approved in decades, and progress has
been slow for the drugs currently in the pipeline.
Several high-cost specialty agents for the treatment of SLE and lupus nephritis (LN) are currently under development, including:
• Ocrelizumab—an intravenous humanized anti-CD 20 monoclonal antibody that recruits the body’s immune system
to attack and destroy B-cells. However, development of this drug for the treatment of lupus has been suspended due
to adverse events in Phase III trials.
• Belimumab—an intravenous monoclonal antibody that inhibits the biologic activity of the protein B-lymphocyte
stimulator (BLyS). BLyS is necessary for the maturation and survival of B-cells into antibody-producing cells. Elevated
levels of BLyS occur in patients with SLE, perhaps increasing self-antibody production and disease activity. By blocking
this protein, belimumab may reduce the signs and symptoms of SLE. Positive results from two large Phase III trials, BLISS
52 and BLISS 76, have recently been released, and an NDA for this drug could be submitted before the end of 2010.
• Epratuzumab—an intravenous monoclonal antibody directed against the CD-22 antigen on B-lymphocytes. Similar
to belimumab, epratuzumab is aimed at decreasing antibody production that may be involved in the pathogenesis
of SLE. Phase III trials are expected to start in 2010, and an NDA filing may not take place until 2012.
If approved for treatment of SLE or LN, these new high-cost biologics will increase utilization and costs in the musculoskeletal
and rheumatological drug category, and they will further augment the list of specialty drugs used for rheumatological
conditions. The new drugs will likely be used in addition to current therapies or possibly as part of the induction regimen
for these conditions. They will not likely provide cures, but they may help ameliorate some of the symptoms, reduce organ
damage, and permit a reduction in the dose of long-term corticosteroid therapy, which is often needed to keep this disease
from flaring up.
table 11.
some ambulatory-use musculoskeletal and rheumatological agents in the pipeline
potential impact
on drug trend
year
generic name
uses
2010
bazedoxifene
denosumab
pegloticase
Osteoporosis
Osteoporosis
gout
$
$$
$$
2011
bazedoxifene + conjugated estrogen
lasofoxifene
belimumab
Osteoporosis, postmenopausal symptoms
Osteoporosis
Systemic lupus erythematosus (SLE)
$
$
$
cp-690550
odanacatib
ospemifene
epratuzumab
rheumatoid arthritis
Osteoporosis
Vaginal atrophy
SLE
$
$
$
$$
2012
$ = potential to cause a <2% increase in this category’s trend.
65
WHERE TO FOCUS NEXT
Respiratory agents
Drug trend projection for respiratory agents*
table 12. Year
2010
Annual total
0% to 1%
3% to 4%
3% to 5%
2011
0% to 1%
5% to 6%
5% to 7%
2012
0% to 1%
6% to 7%
6% to 8%
Trend predictions
Key developments that are likely to shape drug trend in the respiratory chapter over the next 3 years:
• Introduction of new corticosteroid/long-acting bronchodilator combination products to compete with
Advair Diskus® and Symbicort®
• New treatments for chronic obstructive pulmonary disease (COPD), hereditary angioedema (HAE),
pulmonary arterial hypertension (PAH), and cystic fibrosis (CF)
• First-time generics for the blockbuster drug, Singulair®
• Limits on long-term use of long-acting bronchodilators, such as Serevent®
Trend driver: New treatments for pulmonary diseases, including COPD, PAH, and CF
Trend moderators: Nonsedating antihistamines, generics for Singulair
Pipeline drugs: Some of the primary respiratory drugs in the pipeline are shown at the end of this section (Table 13)
> Asthma and chronic obstructive pulmonary disease (COPD)
Treatment trends
The use of single-entity long-acting bronchodilators, such as Serevent® Diskus® and Foradil®, has continued to decline in
response to concerns about an increased risk of asthma exacerbations and asthma-related deaths associated with these
drugs in the treatment of asthma.72, 73 Long-acting beta-agonists (LABAs) are contraindicated as monotherapy for asthma,
and should only be used in combination with inhaled corticosteroids in moderate-to-severe persistent asthma.74 The FDA
has advised healthcare professionals to prescribe inhaled corticosteroids as first-line controller therapy and to add longacting bronchodilators only if inhaled steroids are inadequate to achieve control.
In 2010, the FDA issued new warnings about use of long-acting bronchodilators alone to treat asthma, advising that they
should be discontinued once control is achieved with a preferred controller, such as an inhaled corticosteroid.75 The new FDA
warning could have implications for the long-term use of combination products like Advair for some patients with asthma.
Practice guidelines have not yet been defined with regard to discontinuing LABA treatment for patients who have been on
a combination treatment and whose asthma is now well-controlled. Practice policies for these patients need to be deferred
until the FDA and manufacturers complete the label update and professional organizations have a chance to comment on
the changes.
66
> 2010
WhErE to focus NExt
New treatments for asthma and copd
Despite concerns about their safety, several LABAs are still in development, although they are likely to be indicated first for
COPD, and only later for asthma as part of combination products with inhaled corticosteroids. Indacaterol is a once-daily
LABA with a rapid onset of action (approximately 5 minutes) that may be approved for COPD in 2011. Pipeline developments
for COPD may also include combination products containing once-daily drugs with complementary actions, such as a longacting anticholinergic drug combined with a long-acting inhaled corticosteroid.76
An inhaled formulation of the anticholinergic drug glycopyrrolate is being developed as a new treatment for COPD. Inhaled
glycopyrrolate can be administered once daily and may have a faster onset of action than the anticholinergic medication,
Spiriva® (tiotropium), although it is still unknown if this will translate into improved efficacy. Inhaled glycopyrrolate could
reach the market in 2012, and the manufacturer is also developing a combination product with indacaterol that could reach
the market after 2012.
Daxas® (roflumilast) could be the first in a new class of agents for COPD. This once-daily oral drug is a selective
phosphodiesterase IV inhibitor that has both anti-inflammatory and vasodilation properties. However, efficacy in clinical
trials has been modest and tolerability has been an issue due to the high doses needed for a response. If approved,
roflumilast is likely to be indicated for patients with more severe COPD who have frequent exacerbations, and it may be
used in combination with currently available therapies. Roflumilast could reach the market as early as 2010.76
Several inhaled corticosteroid/bronchodilator combinations may reach the market in the next few years, providing some
additional competition for Advair®. Dulera® (mometasone/formoterol) has a twice-daily administration schedule and is
expected to reach the market in late 2010 for both asthma and COPD indications. Flutiform® (fluticasone/formoterol) is also
designed for twice-daily administration and is expected in 2011 with an indication for asthma only. Finally, fluticasone plus
642444 (another LABA) could be the first once-daily inhaled corticosteroid/bronchodilator combination to reach the market.
This would offer increased convenience over existing combinations, which are all dosed twice daily. The new combination
product could reach the market in 2012.
first-time generics
No inhaled corticosteroid or inhaled corticosteroid combination products are currently expected to become available
in generic form during the next 3 years due to the current lack of bioequivalence standards for inhaled corticosteroids.
Considering that billions of dollars are spent on inhaled corticosteroids and LABA/corticosteroid combinations, FDA
standards to approve bioequivalent generics for these drugs are surely needed to help create more competition in this space.
Generic albuterol inhalers, which were available for many years, completely disappeared in 2009, as the market transitioned
from CFC-based to HFA-based inhalers. The HFA-based inhalers have gained extended patent life because of the new
propellant used in the products. Some of the patents for these HFA products will expire in 2010, but any generics that enter
the market will only need to pick one of the three available brands as the reference standard. Therefore, any new generic
for these HFA inhalers might be substitutable for only one of these brands, rather than all three.
When generics become available for Singulair (montelukast) in 2012, the asthma category will experience a significant
reduction in unit costs. Singulair is one of the leading asthma controller medications; in 2009, it accounted for 2.3 million
prescriptions and over $3.4 billion in sales in the United States.13
> pulMoNary artErial hypErtENsioN (pah)
Spending in this specialty category has been growing rapidly due to the high cost of PAH treatments and the growing
use of combination therapy to treat this condition. In the past, these expensive therapies were often billed under the
medical benefit, since some of the drugs used to treat PAH are administered parenterally. However, as more oral drugs and
inhaled medications to treat PAH become available, the costs of PAH treatment are shifting to the pharmacy benefit. Two
new products were approved in 2009—Tyvaso®, an inhaled formulation of treprostinil that is administered via portable
nebulizer, and Adcirca®, a form of tadalafil, a phosphodiesterase-IV inhibitor, that has been marketed as Cialis® for the
treatment of erectile dysfunction.
67
No new drugs for the treatment of PAH are likely to come to market during the next 3 years. Some new drugs, including
a next-generation version of Bosentan®, are in development, but none are expected to reach the market until after 2012.
> Allergic rhinitis
First-time generics for Clarinex® (desloratadine) and Clarinex-D® (desloratadine/pseudoephedrine) are expected to reach
the market in 2012. However, as with other prescription antihistamines, this product may be converted to OTC status before
the generic products are introduced. Utilization and costs for nonsedating antihistamines are expected to continue to
decline over the next 3 years as patients migrate to new and existing OTC products.
> Cystic fibrosis (CF)
Several new agents may be introduced for the treatment of CF over the next few years. Two antibiotic products are being
developed to control or prevent Pseudomonas infections, which are particularly common and problematic in this disease.
Aztreonam inhalation (Cayston®), an antibiotic for administration via nebulizer, was approved in February 2010. Cayston
may improve lung function and delay the need for other antibiotic treatments in CF patients with Pseudomonas aeruginosa
infections in the lungs. A new dry-powder inhaler formulation of tobramycin may be available in 2012, also for the treatment
of P. aeruginosa lung infections. Tobramycin is already available for delivery via nebulizer, but a dry-powder inhaler would
offer greater convenience and eliminate the need for a nebulizer.
Two additional new drugs are being developed for patients with CF to help clear the lungs of thick mucus secretions,
which can contribute to bacterial infections. Bronchitol® is an inhaled formulation of mannitol that helps hydrate mucus
secretions, thus facilitating clearance from the lung. Bronchitol is administered twice daily using a dry powder inhaler and
is expected to reach the market in 2011. Denufusol, another mucus-clearing agent, stimulates the P2Y2 receptor in the
lungs, resulting in increased fluid content and enhanced mucociliary clearance of secretions. Denufusol could reach the
market in 2012.77
> Idiopathic pulmonary fibrosis (IPF)
Pirfenidone, an oral agent that inhibits collagen synthesis, is being developed as a treatment for IPF, a rare and serious
respiratory disorder. The two pivotal Phase III trials for this drug provided discordant results in terms of efficacy for IPF, so
there is some question about how these results will be interpreted by the FDA. If approved, pirfenidone will be the first drug
ever approved for treatment of IPF. It is likely to be a very high-cost specialty drug, since this is a rare condition with few
effective treatment options.
> Hereditary angioedema (HAE)
HAE is a rare genetic disorder characterized by recurrent, unprovoked episodes of severe edema involving the face, larynx,
extremities, and abdomen.78 Although rare, the disorder has been a hotbed for new drug development. In 2008, Cinryze®
(a C1 esterase inhibitor) was approved for prevention of HAE episodes. In October 2009, Berinert® (a C1 esterase inhibitor
similar to Cinryze) was approved for treatment of acute HAE attacks affecting the face and abdominal area. Both Cinryze
and Berinert are administered by intravenous infusion. In November 2009, a third drug, Kalbitor®, a kallikrein inhibitor that
is administered via subcutaneous injection, was approved for the treatment of acute HAE attacks.79
New drugs in development for HAE include icatibant, a bradykinin antagonist, which is being developed as a prefilled
syringe for subcutaneous injection. Bradykinin is believed to be one of the major mediators of the edema that characterizes
this condition. Approval of icatibant is expected in 2011.
Although utilization of these agents is likely to be small because HAE is a rare condition, payment for these new drugs under
the pharmacy benefit is likely to contribute to unit-cost growth in the respiratory category.
68
> 2010
table 13.
some ambulatory-use respiratory agents in the pipeline
generic name
uses
2010
mometasone + formoterol
roflumilast
pirfenidone
alpha 1 antitrypsin
Asthma
Asthma, chronic obstructive
pulmonary disease (COPD)
idiopathic pulmonary fibrosis
Emphysema
$$
$$
2011
mannitol inhalation
icatibant
indacaterol
fluticasone + formoterol
levalbuterol + ipratropium
Cystic fibrosis
Hereditary angioedema
Asthma, COPD
Asthma
COPD
$
$$
$
$
$
2012
denufosol inhalation
tobramycin inhalation powder
fluticasone + 642444
glycopyrrolate inhalation
Cystic fibrosis
Cystic fibrosis
COPD
COPD
$
$
$
$
WhErE to focus NExt
potential impact
on drug trend
year
$
$
69
WHERE TO FOCUS NEXT
Oncology agents
table 14.
Drug trend projection for oncology agents*
Year
2010
Annual total
1% to 2%
11% to 12%
12% to 14%
2011
1% to 2%
11% to 12%
12% to 14%
2012
1% to 2%
11% to 12%
12% to 14%
Trend predictions
Key developments that are likely to shape drug trend in the oncology chapter over the next 3 years:
• Increased treatment of cancer as a chronic disease involving long-term, daily therapy with anticancer drugs
• Patients moving from one targeted therapy to the next as their cancer progresses
• New injectable monoclonal antibodies to treat various cancers
• The first therapeutic cancer vaccine product
Trend driver: Several new cancer drugs, including oral multi-kinase and vascular endothelial growth factor
(VEGF) inhibitors, and monoclonal antibodies
Trend moderators: Several first-time generics, including Femara® (letrozole), Arimidex® (anastrozole), and
Temodar® (temozolomide)
Pipeline drugs: Some of the primary oncology drugs in the pipeline are shown at the end of this section (Table 15)
The oncology chapter includes a diverse group of cancer drugs: injectable cytotoxic chemotherapy, monoclonal antibodies,
other injectable drugs to treat cancer, and many newer oral drugs. This chapter is unique in that a very large part of the costs
for these drugs is paid for under the medical benefit, rather than under the pharmacy benefit. Therefore, some of the costs
may be “hidden” on the medical side and may not be as readily apparent to plans as other areas of drug therapy.
Scientists have begun to develop more targeted drug therapies and diagnostic tests that are transforming how cancer is
treated. Biomarker and genetic testing is becoming more common in the oncology arena—for example, testing patients
for polymorphisms in CYP450 metabolizing enzymes to identify poor metabolizers of tamoxifen. The FDA recently held an
Oncology Advisory Committee meeting to discuss clinical trial design for validating biomarkers and selecting patients for
drug use based on this information.80 As more and more information becomes available on the use of genomic and other
biomarkers, cancer therapy is leading the way in the field of personalized medicine.
There are currently over 800 new cancer drugs and new indications for existing cancer drugs in clinical development.81
Consequently, plan costs for oncology drugs, especially the more targeted and long-term oral drugs, will continue to grow
rapidly over the next 3 years. Cancer treatments are now the third largest category of specialty drugs paid under the
pharmacy benefit. However, considering that most cancer treatments are paid under the medical benefit, oncology drugs are
likely the top category for specialty drug spending when payments under the pharmacy and medical benefits are combined.
70
> 2010
WhErE to focus NExt
The marketplace tolerance for the high cost of cancer drugs seems greater than in many other areas of drug therapy. More
than 90% of the anticancer drugs approved during the last 4 years exceed $20,000 for a 12-week course of therapy.82 A
recent survey of medical oncologists indicates that the rising costs of cancer drugs—and patients’ out-of-pocket costs, in
particular—are starting to influence their treatment recommendations.83
The rising costs of cancer drugs are also a growing concern for payers. Cancer drugs often provide only short-term
improvements in progression-free survival (time to cancer progression) or response rate (shrinking of the tumor), rather
than improvements in an outcome (such as overall survival). Also, once a new cancer drug has been approved for one
indication, off-label use of the product for other indications is common, and some of these uses may not be supported
by adequate evidence of efficacy. Off-label uses may be driven more by urgent circumstances and the lack of available
treatment options.
> caNcEr trEatMENt
treatment trends
Older injectable cytotoxic chemotherapeutic drugs, such as doxorubicin or cyclophosphamide, are used for many types of
cancers. These agents need to be administered in a physician’s office, clinic, or hospital by intravenous infusion and are given
in short cycles due to their potential for severe side effects. New, more targeted, and better tolerated orally-administered
cancer drugs are causing a paradigm shift towards long-term maintenance use of these drugs in an ambulatory setting,
rather than the use of short-term cyclic treatments. These oral treatments are expensive—they frequently cost in the range
of $5,000 to $10,000 for only a month of therapy. Many new cancer drugs are used on a long-term basis in addition to or
sequentially with other treatments, so they can be significant drivers of utilization growth.
New, more targeted drugs
New oral and injectable drugs for treating cancer will continue to be important trend drivers over the next few years due
to the large number of drugs in the oncology pipeline. These new drugs, combined with expanded indications for existing
oncology drugs and widespread off-label usage for these products, will drive increased costs in this category. New targeted
cancer treatments in the pipeline include oral multi-kinase inhibitors, oral VEGF inhibitors, and injectable monoclonal
antibodies.
Multi-kinase inhibitors
Multi-kinase inhibitors are small-molecule oral drugs designed to inhibit the growth and proliferation of tumor cells by
targeting various pathways that promote tumor development. There are a wide variety of these drugs, both on the market
and in the pipeline. Gleevec® was the first multi-kinase inhibitor to be approved. One of the indications for this drug is for
treatment of Philadelphia chromosome–positive chronic myeloid leukemia (CML). Gleevec significantly improved patient
survival and dramatically changed how CML is treated, turning an acute and often fatal illness into a chronic condition that
can be managed with long-term oral therapy.
Over the past few years, a large number of additional drugs in this class have been approved. Nexavar® is approved for the
treatment of advanced renal cell and liver cancers. Sutent® is approved for advanced renal cell cancer and gastrointestinal
stromal tumor (GIST) after failure with Gleevec. Tykerb® is approved for advanced or metastatic breast cancer after
Herceptin® fails or in combination with Femara® as first-line therapy. Sprycel® and Tasigna® are both approved for Gleevecresistant CML. These drugs may soon be approved for additional indications, further contributing to utilization and unitcost growth in this category.
Several new oral multi-kinase inhibitors are in late-stage clinical development and may receive FDA approval over the next
several years. These pipeline multi-kinase inhibitors include motesanib for lung and breast cancer, bosutinib for CML and
breast cancer, axitinib for renal cell carcinoma, and cediranib for colorectal cancer.
71
Vascular endothelial growth factor (VEGF) inhibitors
VEGF inhibitors are designed to starve the cancer cells of oxygen and nutrients by inhibiting the growth and development
of tumor-feeding blood vessels. The VEGF inhibitor Avastin® (bevacizumab) is an injectable monoclonal antibody that is
FDA-approved in combination with other therapies for the treatment of advanced colorectal cancer, metastatic lung cancer,
and metastatic human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. In 2009, Avastin also
received FDA approval for the treatment of metastatic renal cell carcinoma in combination with interferon, and for the
treatment of glioblastoma (an aggressive type of brain cancer). Avastin is already a multi-billion dollar drug and these new
indications will continue to fuel the costs associated with its use.
Another oral VEGF and multi-kinase inhibitor, pazopanib (Votrient®), was approved by the FDA toward the end of 2009 as
a once-daily oral drug for the treatment of renal cell cancer. In the last few years, about six new oral or injectable drugs
have been approved for the treatment of renal cell carcinoma. Some of these drugs will be used sequentially; as renal
cell carcinoma progresses on one drug, patients will be transitioned to the next one. Pazopanib is also under clinical
development for other types of cancers, including breast cancer.
Monoclonal antibodies
Monoclonal antibodies are highly selective protein-based injectable drugs that selectively target and attach to specific
receptors on cancer cells, thereby helping the body’s immune system attack and kill or inhibit the growth of the tumor.
Rituxan was one of the first monoclonal antibodies developed for the treatment of cancer, specifically non-Hodgkin’s
lymphoma, and in March 2010 was indicated for lymphocytic leukemia. Other monoclonal antibodies approved for the
treatment of various cancers include Herceptin® for breast cancer, Erbitux® for colon and head and neck cancer, Vectibix®
for colon cancer, and Mylotarg® for acute myelogenous leukemia (AML). These drugs are often given in combination with
traditional chemotherapy to achieve the greatest benefit.
All of these monoclonal antibodies are in clinical development for the treatment of other cancers, including Vectibix for
head and neck cancer and Erbitux for pancreatic and lung cancers. Thus, some of these drugs may receive additional FDA
indications over the next several years.
A new monoclonal antibody, Arzerra™ (ofatumumab), was approved by the FDA toward the end of 2009 for the treatment
of chronic lymphocytic leukemia in patients who have failed to respond to other medications. Additional monoclonal
antibodies are currently in clinical development, including ipilimumab, a monoclonal antibody targeting cytotoxic
T-lymphocyte antigen-4, to be used for treatment of metastatic melanoma.
Therapeutic cancer vaccines
Therapeutic cancer vaccines are an emerging field of cancer therapy. These vaccines provide a unique and highly
personalized way of treating certain types of cancer by stimulating the body’s own immune system to recognize and attack
the patient’s tumor. Unlike other vaccines that are used to prevent a disease from developing in the first place, a therapeutic
cancer vaccine is used as part of the treatment for an existing condition. These vaccines typically use a piece of the tumor
or a tumor-specific chemical as the antigen (a substance that can provoke an immune response).
The objective behind these vaccines is to train the body’s immune system to recognize the cancer as foreign to the body, so
that the immune system will attack it. One advantage of such an approach is that once the immune system is stimulated to
attack the tumor, there can be ongoing surveillance by the immune system to destroy the tumor if it recurs. This approach
could provide a long-term deterrent against return of the cancer.
Sipuleucel-T (Provenge®) is a therapeutic vaccine that is designed to activate the patient’s own immune defenses against
hormone-refractory prostate cancer. Sipuleucel-T is produced by taking cells from the patient’s immune system, sensitizing
them to a substance typically produced by the tumor, and then returning them to the patient to provoke an immune
response against the tumor. The manufacturer has submitted a BLA for this novel therapeutic approach to treating
advanced, hormone-refractory prostate cancer, and this highly personalized medicine could be approved by the middle
of 2010. Other therapeutic vaccines for cancer are also in development. Therapeutic vaccines to treat B-cell lymphoma are
among those that are closest to market availability.
72
> 2010
> supportivE carE
WhErE to focus NExt
Use of erythroid stimulating agents (ESAs), such as Epogen® and Aranesp®, has continued to decline as a result of FDA
warnings and product label changes that have led to reduced use of these drugs for chemotherapy-induced anemia. In
February 2010, the FDA announced new REMS requirements for these agents, known as “Assisting providers and cancer
patients with risk information for the safe use of ESAs” (APPRISE). These new requirements will help highlight the fact
that ESAs may cause tumors to grow faster and cause some cancer patients to die sooner. Although the program is
not mandated for patients with chronic kidney failure, the program does highlight the risk of stroke, heart attack, heart
failure, and blood clots associated with these drugs in all patients, not just cancer patients. When this new program is
implemented, use of ESAs is likely to decline further, especially in the cancer-related marketplace.
L-glutamine (Saforis®), a potential new drug for chemotherapy-induced mucositis (painful mouth sores), was submitted for
FDA approval last year. However, the FDA has requested an additional clinical trial before the drug can be approved. If the
manufacturer successfully completes and submits the required study, this drug could become the second FDA-approved
drug to treat one of the most common complications associated with chemotherapy.
Two new drugs used to treat low platelet count in patients with idiopathic thrombocytopenic purpura (ITP), Nplate® and
Promacta®, were approved toward the end of 2008. Both of these medications are also under clinical development for
chemotherapy-induced thrombocytopenia. If the clinical data are positive and these drugs are approved for this use, their
utilization could increase significantly since available options to treat chemotherapy-related thrombocytopenia are mostly
limited to platelet transfusions.
first-time generics
Several first-time generics may be approved in the oncology category over the next few years. These include Femara®
(letrozole) and Arimidex® (anastrozole) for breast cancer, and Temodar® (temozolomide) for brain and skin cancers. However,
these drugs are not significant drivers of trend in the category, so the impact of the generic conversions will be small.
Increased utilization and costs associated with new oncology drugs will exceed the savings from these new generics.
73
table 15.
Some ambulatory-use oncology agents in the pipeline
Potential impact
on drug trend
Year
Generic name
Uses
2010
eribulin
omacetaxine
pixantrone
sipuleucel-T
Breast cancer
CML
Non-Hodgkin’s lymphoma
Prostate cancer vaccine
$
$
$
$
2011
patupilone
alvocidib
carfilzomib
L-glutamine suspension (Saforis®)
cediranib
cabazitaxel
histamine dihydrochloride
ipilimumab
pertuzumab
Ovarian cancer
Chronic lymphocytic leukemia
Multiple myeloma
Chemotherapy-induced mucositis
Colon cancer
Prostate cancer
AML
Melanoma
Metastatic HER2 breast cancer
$
$
$
$
$
$
$
$
$
2012
abiraterone
BiovaxID®
bosutinib
CDX-110
motesanib
axitinib
lonafarnib (Sarasar®)
Prostate cancer
Non-Hodgkin’s lymphoma
CML
Glioblastoma
Breast cancer, thyroid cancer
Renal cell cancer
Breast cancer, myelodysplastic
syndromes
$
$
$
$
$
$
$
WHERE TO FOCUS NEXT
Other areas of drug development
In addition to the drugs mentioned in the top 6 therapeutic chapters, there are many other interesting drugs in the
pipeline (Table 16). These include the following areas of new drug development:
• A pipeline drug to treat premature labor
• Several new drugs used to treat hepatitis C infection
• Several drugs to treat inherited enzyme deficiencies, such as Gaucher’s disease, Fabry’s disease, and Pompe’s disease
• At least two new drugs for psoriasis
• At least three new drugs to promote weight loss
• Several drugs to treat male and female sexual dysfunction, including male erectile dysfunction, premature ejaculation,
and female hypoactive sexual desire disorder
• Multiple drugs to treat eye disease, such as macular edema and macular degeneration, posterior uveitis, and glaucoma
• Several orphan drugs to treat myelofibrosis, urea cycle disorders, and Huntington’s disease
74
> 2010
table 16.
other therapeutic categories: some ambulatory-use drugs in the pipeline
generic name
uses
2010
17 alpha-hydroxyprogesterone injection
albuferon
alglucosidase alfa
motavizumab
Premature labor
$$
$
$
$
phentermine + topiramate
taliglucerase alfa
tesamorelin
Hepatitis C
Pompe’s disease
Prophylaxis of respiratory syncytial virus
infections
Obesity
gaucher’s disease
HiV lipodystrophy
2011
agalsidase
alprostadil topical gel
avanafil
linaclotide
lorcaserin
mepolizumab
naltrexone + bupropion Sr
reslizumab
vicriviroc
voclosporin
fabry’s disease
Constipation-predominant iBS
Obesity
Hypereosinophilic syndrome
Obesity
Eosinophilic esophagitis
HiV/AiDS
Posterior uveitis
$
$
$
$
$
$
$
$
$
$
2012
aBt-874
afilbercept
apremilast
apricitabine
AZD3355
boceprevir
cyclosporine ocular implant
dapoxetine
eliglustat
esmirtazapine
flibanserin
hpN-100
iNcB18424
lidocaine/prilocaine
migalastat
mirabegron
ospemifene
pridopidine
telaprevir
testosterone gel
udenafil
vedolizumab
Chronic plaque psoriasis
Age-related macular degeneration
Chronic plaque psoriasis
HiV/AiDS
gastroesophageal reflux disease
Hepatitis C
Prevention of corneal transplant rejection
Premature ejaculation
gaucher’s disease
Postmenopausal symptoms
female hypoactive sexual desire disorder
urea cycle disorders
Myelofibrosis
Premature ejaculation
fabry’s disease
urinary incontinence
Vaginal atrophy
Huntington’s disease
Hepatitis C
Hypoactive sexual desire disorder
Crohn’s disease
$
$
$
$
$
$$
$
$
$
$
$
$
$
$
$
$
$
$
$$
$$
$
$
WhErE to focus NExt
potential impact
on drug trend
year
$
$
$
75
W H AT ’ S N E X T
IN HEALTHCArE
THE WAy ForWArd
What’s NExt iN hEalthcarE
the u.s. healthcare system is broken: costs continue to rise unsustainably
without commensurate quality improvements. fragmented care that rewards
high-volume over high-quality and acute intervention over wellness is to
blame. What can be done to solve the cost/quality equation? Wiring healthcare
infrastructure is the first step forward.
Some providers are making great strides by transitioning away from the
traditional fragmented delivery system towards a wired, collaborative model.
Such collaborative care-delivery models, which lay the groundwork for smarter
medicine, improve the quality of care and moderate cost. Here we explore how
wired healthcare delivery supports leadership in collaborative care,
women’s health, and personalized medicine.
W H AT ’S N E XT I N H E A LT H C A r E
T H E WAy F o r WA r d
What are we facing now?
Healthcare costs in the United States continue to escalate for both patients and payers. National health expenditures (NHE)
increased 4.4% to $2.3 trillion in 2008 accounting for 16.2% of national gross domestic product (GDP). NHE projections due
out this year estimate a 5.7% increase accounting for 17.3% of GDP.1 America spends an average of $7,681 per capita annually
on healthcare, almost double that spent by most other industrialized countries. Escalating expenses result in part from
rising chronic disease rates, inefficient delivery, and regional variation in service use and service costs. A recent estimate
determined that 75% (at the time $1.7 trillion) of the total healthcare cost was spent on treating chronic and complex
diseases.2 As a country, we spend more than twice as much on healthcare compared to food ($1 trillion).2 What can be done?
The Commonwealth Fund suggests the following solutions:3
• Wiring the care-delivery system to improve provider and patient access to clinically relevant patient information
• Coordinating patient care across provider settings
• Developing collaborative care models to deliver high-quality and high-value care
• Implementing performance assessments and feedback systems to improve the quality and value of care delivery
• Holding providers accountable for the total care of the patient
• Enabling easy access by offering extended hours and culturally competent care
Trailblazing organizations, both public and private, are developing the means to realize affordable, quality healthcare for
their employees and members. Informed by technology, these leaders employ collaborative models to deliver care that
meets unique patient needs. Specifically, they have:
• Implemented health information technology (HIT) to contain costs, and to improve and measure quality
• Recognized the patient-centered collaborative care model as a more efficient and effective care-delivery system
compared to the traditional model
• Integrated the practice of protocol-driven care to reduce cost, prevent treatment errors, and improve quality
• Evolved the traditional one-size-fits-all delivery model in favor of personalizing care based on unique patient needs
77
Wired collaborative care for the whole patient
A number of preventive and patient-centered care models have emerged in recent years. Collaborative care provides
optimal efficiency by focusing on appropriate, timely, and preventive treatment. This model relies heavily on the use of
information technology to enhance communication across providers and patients and ensures ready access to clinical
information. 4 Successful collaborative care pilot programs employ a wired infrastructure, evidence-based protocols, and
financial incentives tied to quality benchmarks.5
Collaborative care is rooted in what the American Academy of Pediatrics introduced in 1967 as the “medical home.” The
medical home has traditionally included the primary care provider, typically a physician or a nurse practitioner. However, it
also engages an extended healthcare team, including clinical specialists, pharmacists, patient advocates, health insurance
plans, and benefits coordinators, to expand and support the medical home. Leaders in collaborative care recognize the
vital roles that all members of the healthcare team play in supporting the doctor-patient relationship and delivering more
effective care.
> What is collaBorativE carE?
The concept of collaborative care is an approach to providing primary care that is coordinated, accessible, comprehensive,
and patient-centered. A collaborative care model ensures that each provider has unencumbered, real-time access to all
the records related to every aspect of a patient’s care. In addition to improving clinical outcomes, collaborative care models
can effectively reduce wasteful spending incurred from duplicative laboratory or diagnostic testing and close gaps in care.
The Joint Principles of the Patient-Centered Medical Home6, 7 have formed the basis of current collaborative care models.
These fundamental principles include:
• Coordinated primary care ensures well-orchestrated delivery of all primary care, whether acute or chronic, irrespective
of the clinical setting.
• Patient-centered care is tailored to the needs and preferences of individual patients who are engaged in the clinical
decision-making process. As the focus of the treatment model, patients must also have flexible options in accessing
their care, which could include Internet-based “visits” and evening hours.
• Transparency is designed to improve safety and accountability through evidence-based, protocol-driven clinical
practices that are available to all care providers.
• Payment reform refers to a shift from fee-for-service to a pay-for-performance approach that includes appropriate
payment structures for care coordination and technology-based consultations.
> WirEd collaBorativE carE: thE road Map for iMprovEd outcoMEs
Moving toward a protocol-driven healthcare system requires both defined metrics and a means for frictionless
information exchange. Once the protocols are in place, collaboration follows more smoothly. Standard protocol
implementation via decision support has also shown measurable outcome improvements. In a study that evaluated
the use of HIT to integrate decision support systems, every 10-point increase in the use of these systems created a 16%
reduction in the frequency of complications and a 15% reduction in the number of in-hospital deaths. In addition, perpatient hospital costs dropped by $538.8
Electronic medical records (EMRs), which include a history of clinical services a patient uses within a specific care-delivery
organization, streamline the use of existing paper medical records and enhance communication, coordination, and
decision support within hospital and ambulatory settings.
78
> 2010
Electronic health records (EHRs), which include a history of the clinical services a patient uses across several care-delivery
organizations (i.e., the summary of EMRs), can be shared across multiple care-delivery organizations within a community,
region, or state to provide a comprehensive history of an individual’s health.9 The use of EHRs is an important tool in
facilitating the success of collaborative care: They remove geographic barriers, empower consumers, and improve reliability.
However, only about 17% of U.S. physicians and 8% to 10% of U.S. hospitals use a basic EHR system, in part because of
concerns about the costs of implementation and lack of standards to assure interoperability across healthcare settings.
Providers often view implementation as a major change in their practice or operation that will initially be highly disruptive
to existing work-flows and result in inefficiencies during the startup or adoption phase. By comparison, 80% to 100% of
primary care physicians in Europe, New Zealand, and Australia use EHRs.10 Transforming a paper-based record system to an
electronic infrastructure is costly and time-consuming and, without standards, could result in operability conflicts.
Ideally, EMR and EHR systems are “interoperable”—data can be exchanged and received according to a standardized
coding format shared by all systems involved. One example of the value of EMRs is within the computerized physician
order-entry system, which allows physicians to order tests, medications, and services, and to make referrals electronically.9
Electronic prescribing (e-prescribing), an application of computerized physician order entry, enables prescribers to send
prescriptions directly to the pharmacy from the point of care.11 These systems also alert the physician to formulary options
and prior authorizations, which can eliminate work steps and help reduce costs for patients and payers. Systems could
also include various quality controls and drug interaction safety checks. The inclusion of e-prescribing in the Medicare
Modernization Act of 2003 highlighted the importance of this innovation in improving the quality of patient care. As
e-prescribing systems have become widely available, their use has begun to increase, virtually doubling in use yearly. A
recent study funded by the Agency for Healthcare Research and Quality estimated that e-prescribing allows physicians
to select less-expensive medications that can save private insurers as much as $845,000 per 100,000 patients per year.12
> rEduciNg WastE aNd closiNg gaps iN carE
Wired, collaborative healthcare delivery can transform the treatment of chronic and complex disease by reducing
waste and closing gaps in care to improve patient outcomes. Deploying HIT to support care delivery opens the door
to innovations in preventive care, chronic disease management, and care coordination.13 Today, preventive care may be
overlooked simply because providers have no electronic systems that would automatically assist in keeping track of the
preventive services each patient requires. Currently, about 54% of Americans are screened for colorectal cancer, 69% for
breast cancer, and 81% for cervical cancer. It is estimated that improving these rates could save up to 45,000 lives per year.13
Wired collaborative care could significantly improve outcomes in chronic disease management. Only 29% of patients
treated for high cholesterol in the United States achieve their cholesterol goal. At Kaiser Permanente of Colorado, the
percentage was even lower (26%). However, by using HIT together with a proactive approach, they helped 73% of their
patients reach their cholesterol goal.13
> lEadErship iN practicE: gEisiNgEr hEalth systEM’s ProVeNHeALTH NAVIgATor sM
Background
The Geisinger Health System, an integrated delivery system in Pennsylvania, serves a largely stable population of 2.5
million people who are generally older, poorer, and less healthy than national indices. Geisinger’s ProvenHealth Navigator
(PHN) is a customized version of the patient-centered medical home, which is increasingly a model for the delivery of
primary care throughout the United States.14 A PHN nurse or case manager is assigned to develop a personal care plan
for each patient. The PHN coordinates care for the patient at every level; reviews medications; ensures that the patient
receives all recommended checkups, screenings, and immunizations; and connects the patient to community resources
as appropriate.
The tool has improved both the patient experience and clinical outcomes—enhancing value in primary care and
promoting efficiency.
79
Key innovations
On-site case managers working at Geisinger Health System care centers use HIT applications to implement standardized
care protocols. The platforms remind case managers of potential topics where patients may need counseling including:
• Smoking cessation, eating and nutrition, exercise
• Medication dosages and interactions
• Managing acute disease situations (e.g., chronic obstructive pulmonary disease [COPD] exacerbations)
• Generic conversion opportunities
Outcomes
Figure 1 shows that during the period 2005 to 2008, emergency room (ER) admissions decreased sharply for patients with
heart failure, diabetes, and COPD who participated in the ProvenHealth Navigator but increased or remained constant for
patients who did not participate.
While the Geisinger innovations may not be suited, point by point, for every healthcare system,15 they offer a successful,
adaptable framework that can be continually revised and renewed to integrate new best practice components with a view
to improving quality and value for patients and their communities.
FIGURE 1.
ProvenHealth Navigator improves clinical outcomes
change in er admissions per 1,000 members from 2005 to 2008
Heart failure
Diabetes
COPD
10
5
change (%)
0
-5
-10
-15
-20
-25
WITH PHN
WITHOUT PHN
Source: Geisinger Health System data
> DUR: Advancing safety through technology and collaboration
Drug utilization review (DUR), a safeguard measure used by pharmacists to screen a patient’s prescriptions, employs
technology to help prevent safety errors in real time. Before dispensing a drug, the pharmacist uses DUR to check for
potential drug interactions, allergies, or other potential medication-related issues. Automatically, the system compares the
new prescription with the patient’s complete medication history to determine whether medicines could interact and cause
a potential hazard. This is particularly problematic because patients are being treated by multiple physicians who are often
unaware of treatments or therapies prescribed by others. When a potential conflict is flagged, the pharmacist can then
recommend an appropriate change in medication. Medco uses a proprietary DUR process. In a 12-month study of seniors
(N=23,269), among whom polypharmacy can present significant safety concerns, computerized DUR identified over 43,000
potential safety concerns resulting in more than 24,000 phone calls to prescribers. As a result of this procedure, medications
were changed by prescribers in 24% of cases, which was much higher than the 2% previously observed.16
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> hit: ExtENdiNg rEach, ExtENdiNg touch
The Medco Extended Enterprise HIT platform enables pharmacists to use real-time pharmacy data when counseling
patients in order to identify and then close gaps in care that could improve clinical outcomes or relay opportunities that
could lower costs. This knowledge is especially beneficial immediately after a diagnosis when a patient is most likely
to phone a Medco pharmacist with medication-related questions or seek information online. The Extended Enterprise
wired capability empowers pharmacists to capitalize on the “teachable moment” arising from the member interaction to
communicate critical medical information at a time when the member is most receptive.
The HIT infrastructure underlying Extended Enterprise focuses on the unique member health action plan (HAP). As Figure 2
shows, the HAP displays, in real time, the list of medications taken by a patient and flags opportunities for further
support. For example, the HAP may identify several opportunities to improve the health of a member with diabetes, such
as prompting the pharmacist to remind the member that his or her plan offers smoking cessation programs and that
the member’s diabetes pharmacist has important health information about the medications the member is taking. The
member can then be transitioned to a Medco Specialist Pharmacist in the Medco Diabetes Therapeutic Resource Center.
That pharmacist has additional training in diabetes care and is best positioned to interact with that particular patient.
Medco research has shown that members readily take advantage of this opportunity. A Medco survey reported that 81% of
participants with a new diagnosis, who received services at a traditional retail pharmacy, either did not receive counseling
or were dissatisfied with the prescription drug counseling they received. When given the opportunity to speak with a
Medco Specialist Pharmacist, 75% of these patients accepted the offer of immediate telephone support.17
FIGURe 2.
real-time view of a patient’s hap
Not actual patient data.
81
W H A T ’ S N E X T in healthca r e
the wa y f o r wa r d
Wiring healthcare for women
As recipients of healthcare based on collaborative models and supported by wired technology, patient benefits are
clear: efficient delivery and improved outcomes. Technological advances across other industries have also enhanced
user experience (e.g., drive-through automated teller machines and automatic bill payment). How could collaborative
healthcare supported by wired technology enhance the healthcare consumer experience?
Research shows that women make most of the healthcare decisions in America today—not only for themselves, but also
for their families as well as their aging parents. Few professional service providers have a comparable opportunity to build
a lifelong “customer relationship.” Nonetheless, surveys reveal that women remain largely dissatisfied with the state of
current healthcare services, especially the care they receive from hospitals and their doctors. The time pressures women
face in their daily lives is at the center of this dissatisfaction.18 Leaders in women’s health have recognized this opportunity
and are implementing creative and wired solutions that are designed to help women meet the demands that come with
busy schedules and multiple responsibilities.
> The sex and gender of disease
We have learned a lot over the past few decades about how sex and gender affect health and disease. In this context, the
term “sex” refers to the biologic aspects of being a woman according to reproductive and chromosomal determinants. The
term “gender” is used to describe more of the social roles and environmental influences of being a woman. Both sex and
gender are important variables in how health or disease processes differ among women or between men and women.
What difference can an X chromosome make? While certain conditions are obviously unique to women, other conditions
that are common across men and women, such as heart disease, can present with very different symptoms. For example,
chest pain or discomfort is a common symptom for men and women that can signal a heart attack. However, women are
more likely than men to experience shortness of breath, nausea/vomiting, and back or jaw pain. Cardiovascular disease
kills 50,000 more women than men each year, and, on average, strikes a decade later in a woman’s life.19 Additionally,
smoking harms women’s hearts more than men’s and women are more likely to suffer severe withdrawal symptoms when
trying to quit. These diseases, not traditionally considered “women’s issues,” underscore the importance of recognizing the
biological differences separating the ways in which men and women experience disease.19
Gender differences, or the social and environmental aspects of being a woman, are equally important to comprehend.
For example, the role of caregiver disproportionately and adversely affects the health of women. Sixty-six percent of
caregivers are women.20 Women spend an average of 20.4 hours per week providing care and making healthcare decisions
for their immediate and extended families.20 The National Alliance for Caregivers survey of self-identified caregivers
showed an increase in the use of medications from 85% in 2004 to 93% in 2009. Seventeen percent of caregivers believed
their health worsened as a result of the caregiving responsibility, which 31% labeled as stressful.20
While women access the healthcare system at a younger age than men, mostly due to reproductive and prenatal needs,
they tend to stay more involved in healthcare decision making as they grow older. Women have higher than average
out-of-pocket healthcare costs than men, spending 68% more on their healthcare during their reproductive years. These
factors combined increase the financial healthcare burden for women. Women are more likely than men to skip medical
care or not fill a prescription because of cost, which in turn may increase their risk of declining health and poor outcomes.21
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> 2010
> lEadErship iN practicE: MEdco WoMEN’s hEalth thErapEutic rEsourcE cENtEr
Background
A Women’s Health Specialist Pharmacist counseled a 59-year-old woman with a history of osteoporosis who appeared to
be nonadherent to her osteoporosis medication.
key innovations
Women’s Health Specialist Pharmacists are trained to understand all aspects of drug therapy used to treat osteoporosis
and the alternatives available.
• The Women’s Health Specialist Pharmacist contacted the patient by phone and probed to determine why she had
not recently filled her osteoporosis medication prescription. During the conversation, the pharmacist learned that the
patient skipped her medicine due to financial hardship caused by a recent co-payment increase. She was also not
taking Vitamin D or calcium due to side effects. Her nonadherence to these medications placed her at risk for fracture.
• The pharmacist counseled the patient on the importance of treating osteoporosis and avoiding the potential risks of
osteoporosis-related fractures. She also informed the patient that a generic alternative to her medication was available
at a significantly reduced cost.
• The patient noted that the calcium supplement was causing constipation and the pharmacist was then able
to recommend an alternative supplement that should not cause constipation. The pharmacist emphasized the
importance of taking the generic medication that could provide similar benefits to the high-cost-brand drug, as well
as calcium and Vitamin D to prevent fractures.
outcomes
With the patient’s consent, the pharmacist faxed a request for the generic medication to the patient’s physician. The
prescription was received back from the physician and was mailed to the patient 3 days after the call, saving considerable
time and out-of-pocket expense for the patient. Reducing the adverse events of osteoporosis can improve quality of life
and reduce total healthcare costs. Generic alternatives save money for both the patient and the plan.
> coordiNatiNg a 360-dEgrEE WoMEN’s hEalth approach
The unique needs of women’s healthcare require greater coordination, more intensive counseling approaches, and a better
understanding of gender-specific treatment protocols—along with cost sensitivity. The pharmacists within the Women’s
Health Therapeutic Resource Center address the sex- and gender-based needs of women through collaborative and
wired protocols and can leverage high-touch interventions to support patients who have chronic and complex diseases.
The Therapeutic Resource Centers model offers collaborative care that considers the entire patient, multiple conditions,
lifestyle factors, and the impact on overall family health—all important treatment considerations for women.
> WirEd collaBorativE carE iMprovEs hEalthcarE for WoMEN
Today there is a renewed sense of urgency for innovation and leadership in designing clinical research studies that are
fine-tuned to meet the needs of women. The National Institutes of Health (NIH) Revitalization Act of 1993 mandated
the inclusion of women and minorities in clinical trials.22 This was the first step that enabled a better understanding of
the diseases and conditions that affect women from a biological and a behavioral perspective, as well as the differences
in the ways that medications interact uniquely for women. The NIH has increased research activity to understand the
differences in women’s health outcomes and disease status related to the role and validation of biomarkers, eating
disorders, hormones, obesity, sleep quality, the use of dietary supplements, and alcohol and drug use or abuse, among
other variables.
83
> Leadership in practice: Dartmouth Hitchcock Norris Cotton Cancer Center
“One of the things I am very interested in is how health information technology can improve our process.”
— E. Dale Collins, M.D., M.S. (Dartmouth Hitchcock Norris Cotton Cancer Center)
Background
Shared decision-making surveys guide patient and clinician discussions so that patients feel informed and empowered
about their breast cancer treatment options.
Key innovations
• The Center for Shared Decision Making is a healthcare system dedicated to helping patients and families make
informed choices about their treatment options.
• An extensive laptop-based questionnaire developed by Dr. E. Dale Collins queries patients about their medical and
family histories and emotional concerns (e.g., depression) and assesses patients’ understanding of their diagnosis,
treatment options, and other factors taken into consideration when deciding on their course of treatment.
• A collaborative care team composed of surgeons, specialists, social workers, facilitators, and nurse coordinators reviews
the survey with the patient and supports the patient throughout treatment selection and delivery.
Outcomes
“Even the best, most dedicated and conscientious clinician occasionally forgets to ask a question, and that one question
may be really important to address. This technology helps to prevent things from ‘slipping through the cracks,’ and
provides crucial data to the care team to ensure that we’re meeting all of the patient’s needs.”
— E. Dale Collins, M.D., M.S.
> Women want more time
Nearly 80% of women in the United States serve as the primary decision maker for their family’s healthcare, and even
more take responsibility for their family’s appointments and make the ultimate selections related to health insurance.
Women are also disproportionately represented in their family’s caregiving responsibilities, typically caring for a sick or
aging relative. This is in addition to serving in primary roles for housework, transportation, and/or financial decisionmaking. Working outside the home may add to women’s responsibilities and the time pressures they feel.
With all of these demands, women are looking to more efficiently and effectively control their time, and healthcare is
no exception. Yet healthcare providers, administrators, and insurance companies have lagged behind other industries in
offering valuable services that accommodate busy lives. For example, financial institutions and retailers offer extended
hours to accommodate work schedules, and they provide concierge services to simplify end-user experiences. In doing so,
many industries have realized that investments to accommodate the convenience and simplification desired by women
also make sound business sense. Wired healthcare initiatives that allow easy access to a patient’s own medical records,
provide the ability to refill and obtain needed prescriptions, simplify administrative logistics, and make medical advice
available 24/7 for women are some solutions that could offer greater convenience and build loyalty.
> Precision medicine for women
Tamoxifen is widely used and considered extremely effective to prevent the recurrence of estrogen-dependent breast
cancer tumors. However, to work effectively, tamoxifen must be metabolized by the liver enzyme cytochrome P450 2D6
(CYP2D6). Some medications, including many antidepressants commonly prescribed with tamoxifen, act as inhibitors of
this process—counteracting the effectiveness of tamoxifen. Approximately 10% of the population has a genetic variation
that also limits the functioning of CYP2D6.
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> 2010
In a large (N=1,298) study, scientists compared women taking tamoxifen with and without selective serotonin reuptake
inhibitors (SSRIs)—a medication that is frequently prescribed for the depression that is linked to the diagnosis of breast
cancer. The same metabolic pathway that enables the body to use tamoxifen to fight the cancer is also used by the SSRI to
combat depression. Some SSRIs fully prevent tamoxifen from working. These SSRIs are called “moderate or potent CYP2D6
inhibitors.” Other SSRIs are “weak inhibitors” of the CYP2D6 pathway; they can be taken with tamoxifen and do not reduce
its effectiveness.
The study results (Figure 3) showed that women who took SSRIs that prevented tamoxifen from working (moderate or
potent inhibitors) suffered approximately twice as many episodes of breast cancer recurrence as those women who took
a weak CYP2D6 inhibitor or who did not take an SSRI.23
It is estimated that 10% of women have genetic differences that prevent medicines like tamoxifen from working. They are
called genetic “poor metabolizers.” The results of this study may also be helpful in predicting what would happen if these
patients were given tamoxifen—a drug that would not work for them: Cancer recurs and time, money, and lives are lost. By
precisely understanding the genetically determined ability of a woman’s body to metabolize tamoxifen or the ways that
drugs may interact, members of a patient’s collaborative care team can ensure appropriate prescribing, facilitate proper
utilization, save money, and most importantly, preserve her life.
FIGURe 3.
Medication interaction leads to higher breast cancer recurrence23
TWo-yEAr brEAST CANCEr rECUrrENCE rATE IN pATIENTS TAkING TAMoXIFEN ANd ANTIdEprESSANTS
No SSRI
Celexa®, Lexapro®, Luvox®
18
16%
recurrence rate (%)
16
14
her
s hig
ime
2.2 t
12
10
8
Paxil®, Prozac®, Zoloft®
8.8%
7.5%
6
4
2
0
No SSRI
Weak CYP2D6
inhibitor SSRI
Moderate or potent
CYP2D6 inhibitor SSRI
The Medco Oncology Therapeutic Resource Center works closely with the Women’s Health Therapeutic Resource Center to
evaluate patients’ comprehensive health needs and overall risk profile. The Medco Oncology Therapeutic Resource Center
is designed to consolidate both traditional and specialty pharmacy cancer-treatment medications to enable a review of
anticancer regimens that include oral cancer medications and supportive therapies to treat nausea and anemia.
85
W H A T ’ S N E X T in healthca r e
the wa y f o r wa r d
Leading the way in personalized medicine
Personalized medicine, or the practice of using diagnostic tests to detect and tailor treatments based on unique individual
genetic variations, holds the promise of making medical care more precise and effective. In addition to elevating clinical
quality, it also contributes to lowering overall healthcare costs. Personalized medicine can optimize drug therapy and help
avoid adverse drug-related reactions. By understanding the genetic markers in an individual patient, a physician has an
indication whether a certain medication would have a high degree of success, which allows the physician to more precisely
select both the medicine and the dose without the “trial and error” that is currently a mainstay of medical practice.
Many adverse drug reactions may be explained by genetic variations in liver enzymes (the cytochrome P450 family)
that metabolize a wide variety of drugs. Warfarin therapy provides one such example. Warfarin is one of the most
commonly prescribed medicines, considered an effective blood thinner. However, precise dosing is critical and, in the
early stages of therapy, patients often need dose adjustments to prevent adverse bleeding events and reduce the risk of
atherothrombotic events such as stroke. In addition to variables such as sex, age, height, and weight, genetic differences
contribute to warfarin treatment response variations. Medco analyses have shown that warfarin dosing issues result in
a 20% hospitalization rate for patients in the initial months of therapy. A simple genetic test can more accurately guide a
physician to more quickly reach the optimal dosing. In one study, investigators suggested that the integration of genetic
testing into warfarin therapy could save more than $1 billion a year in adverse event–related spending.24
A recent Medco study of FDA-approved drug labels reported that25:
• 121 drug labels contained pharmacogenomic information.
• 24.3% (8.8 million) of 36.1 million patients who had prescriptions processed by Medco took one or more drugs labeled
with pharmacogenomic information.
To ensure the integration of personalized medicine into clinical practice, payers and healthcare providers need to embrace
the new science. Today, payers commonly apply a traditional one-size-fits-all model of reimbursement that applies to large,
predictable populations. This must be updated to embrace new actuarial models that consider the unique circumstances
that are now applied to smaller patient populations.26
Physicians need better education and tools to help them incorporate personalized medicine into day-to-day practice.
A recent survey showed that an overwhelming majority of doctors acknowledge that genetics play a role in drug
response, but only a small minority consider themselves well enough informed to use the available genetic tests in the
appropriate situations.
Medco, in collaboration with the American Medical Association, conducted an anonymous, cross-sectional survey
of more than 10,000 physicians to explore the factors that influence the adoption of pharmacogenomics testing.27
• 98% of the responders believed that patients’ genetics can affect drug response.
• Only 10% of the responders believed that they were adequately informed about pharmacogenomic testing.
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> a pathWay to sMartEr MEdiciNE
Medco’s strategy for personalized medicine underscores the importance of using genetic tests when appropriate to help
providers prescribe the most effective medicine at the most effective dose, while improving safety margins, based on each
patient’s genetic profile. In forging the future of pharmacy through personalized medicine, Medco has launched several
studies based on a series of clinical partnerships, including collaborations with the Mayo Clinic, Celera Corporation, and
the FDA.
The Medco-Mayo warfarin collaboration was designed to investigate the economic benefit and the clinical outcomes of
genetic testing to prevent the adverse events of warfarin treatment. The average cost of warfarin-related hospitalization
per patient ranges from $18,000 to $25,000.28 In March 2010, Medco and Mayo reported that hospitalization rates for
patients taking warfarin dropped by approximately 30% when genetic information was available to guide the doctors
prescribing warfarin therapy. More than 58% of patients were found to have genetic profiles that suggested a significant
adjustment in dose was required to achieve an effective level of coagulation.29
A collaboration with California-based Celera Corporation underscores Medco’s commitment to optimize medication
adherence and improve clinical outcomes. Medco and Celera will investigate whether patients who learn they have a
higher genetic risk of heart attack (and other cardiovascular diseases) will become more compliant about taking the
cholesterol-lowering statins they have been prescribed. Statins are the most potent cholesterol-lowering agents available
and the third most commonly prescribed class of drugs in the United States. In 2007, statins ranked number one in
annual cost to Medco clients. Adherence to these medications is needed to obtain the full benefit toward prevention
of cardiovascular disease. Poor adherence accounts for large client drug spending that does not produce the beneficial
outcomes expected by this investment.
Based on clinical trials and new guidelines, statins also play an important role in both the primary and secondary prevention
of coronary heart disease, myocardial infarction, stroke, and peripheral artery disease. Recently, a cardiovascular genetic
marker was discovered that is associated with increased risk for cardiovascular events independent from traditional risk
factors such as low-density lipoprotein, diabetes, and smoking. Medco researchers are investigating whether knowledge
of this second serious risk factor may increase compliance with statin therapy. In 2005, a study to evaluate the impact
of medication adherence on healthcare utilization and cost found that increased adherence to cholesterol medications
results in a decrease to overall medical cost by reducing hospitalizations.30 If knowledge of a genetic risk of heart disease
could improve adherence, a significant reduction in cardiovascular events and the related cost of treatment could
be expected.
> aligNiNg With coMparativE EffEctivENEss rEsEarch
Personalized medicine focuses on the ability to deliver the appropriate treatment to patients based on their unique needs,
whereas comparative effectiveness research examines two or more healthcare services or treatments to determine the
relative effectiveness of those procedures based on scientifically valid methods.
The universal adoption of HIT is required to efficiently orchestrate these two guides—ensuring that a medicine or
procedure used in treatment is proven the most effective for a general population and then ensuring that particular
treatment would be effective for an individual based on that person’s genetic profile. Electronic health records can
effectively capture patients’ genetic and individual health information and ensure that the appropriate evidence-based
and personal information are accessible at the point of care delivery.31
87
As part of its mission to improve patient outcomes and reduce cost, Medco has adopted comparative effectiveness
research to examine the role of genetics in a new concept called Genetics for Generics. This strategy is designed to optimize
the clinical outcomes of generic drug therapy, while lowering overall healthcare costs. The first Genetics for Generics
initiative involves a head-to-head study to determine the effectiveness of a medicine about to become available in generic
formulations compared to a new branded treatment for the same affliction. It is commonly accepted that newer, more
expensive medicines are more effective than older medicines that have transitioned to generic availability. This study will
test whether that is the case for clopidogrel (Plavix®), one of the world’s most widely prescribed medicines that will soon
be available generically, and prasugrel (Effient®), a new brand drug, both approved for the prevention of clots.
> lEadErship iN practicE: PreCISIoN HeALTH SoLuTIoNS™
Genetic testing has the potential to revolutionize the practice of medicine. With the increasing availability of genetic
testing technology comes a need for judicious implementation and support. Testing the wrong person wastes capital and
resources. Administering the wrong test could propagate misinformation and may lead to incorrect diagnoses and wasted
service. Appropriate testing without adequate interpretational support raises ethical questions and may lead to further
wasted resources.
The acquisition of DNA Direct, Inc., by Medco Health Solutions, Inc., expands the Medco portfolio of personalized medicine
offerings into a comprehensive suite of precision health solutions. The enhanced clinical management programs, decision
support tools, benefit design strategies, and DUR ensure the right patient gets the right test with the right interpretation.
FIGURe 4.
Precision Health Solutions strategy
THE RIGHT
PERSON
WHY IT MATTERS:
Finding the right people to benefit
from genomic medicine can improve
disease management and lower
healthcare costs.
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> 2010
THE RIGHT
TEST
WHY IT MATTERS:
Getting the wrong test can
misinform medical decisions and
increase healthcare costs.
THE RIGHT
INTERPRETATION
WHY IT MATTERS:
Delivers the full value of genetic
information and enables physicians
to make appropriate management
decisions.
What’s next?
With escalating healthcare costs and more than 50% of Americans dealing with chronic and complex conditions, it is
clear that healthcare in the United States must change from a model of uncoordinated and fragmented care to a delivery
system that focuses on whole-patient care. Leaders in government and industry must engage strategies to drive greater
value across all aspects of healthcare. Wiring enables the improved efficiencies and outcomes promised by collaborative
care models and enhanced through precision medicine.
A wired collaborative care system facilitates real-time data collection, aggregation, and analysis. Providing integrated
protocol-driven decision-making tools empower physicians, pharmacists, and patients to make treatment decisions
and ensure higher compliance—and offers a means to measure the effectiveness of outcomes. Wired collaborative care
creates efficiencies that can lead to significant improvement in the overall quality of patient care. This is particularly
important in the treatment of chronic and complex disease, which accounts for 96% of all drug spending and 75% of
all medical spending. It will also help to address the systemic costs and problems related to Medicare, reduce the need
among physicians to practice defensive medicine, and eventually encourage tort reform. Over time, these steps combined
with effective prevention and wellness initiatives could reduce per-capital healthcare spending in the United States by as
much as $1 trillion a year.
Part of transforming healthcare requires that we recognize and respond to healthcare utilization patterns across specific
patient populations, such as women, and then transition from a population-based model of care delivery to one of
personalized care.
The Medco therapeutic resource centers® form the foundation of a pharmacy model that has demonstrated the power
and effectiveness of wired, protocol-driven, and evidence-based clinical care. The Medco therapeutic resource centers
model has:
• Closed clinical gaps in care for multiple conditions by matching real-time data against protocol-driven healthcare
• Improved patient health outcomes while reducing overall costs
• Coordinated communication among payers, providers, patients, and pharmacies
Wiring all elements of the healthcare system—physicians, pharmacists, payers, patients, hospitals, laboratories, and other
entities—is the way forward so that the American healthcare system will once again lead the world in providing highquality care for patients while delivering greater value to payers.
The time for next is now.
89
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> influeNcing what’s next | 2009 trend in perspective
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12. Fischer MA, Vogeli C, Stedman, M, Ferris T, Brookhart MA, Weissman JS. Effect of Electronic Prescribing With
Formulary Decision Support on Medication Use and Cost. Arch Intern Med. 2008;168(22):2433-2439.
13. Park T, Basch P. A historic opportunity wedding health information technology to care delivery innovation and
provider payment reform. Center for American Progress. May, 2009. http://www.americanprogress.org/
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99
We would like to acknowledge the following people for their
outstanding contributions to the 2010 Drug Trend Report:
Jack A. Smith, M.A.
Jane F. Barlow, M.D., M.P.H., M.B.A.
Susan O’Connor, B.S.N., M.B.A.
Tiffany Boyd-Hodgson, Ph.D.
Brad Epstein
James Wintraub
Mark Puzio
Libby Mell
Keith Bradbury, R.Ph., M.S.
Kevin Cleary, Pharm.D., M.B.A.
Bill Dreitlein, Pharm.D.
Mark Boyer
Michael Elefonte
Publisher, Chief Medical Officer
Publisher, Chief Marketing Officer
Executive Project Sponsor
Editor in Chief
Managing Editor, Senior Writer
Chief Creative Officer
Creative Director
Associate Creative Director
Project Manager
Senior Writer
Contributing Writer
Contributing Writer
Senior Editor
Senior Production Manager
Analytic support
George Casagrand
Kai C. Chan
Al DeCarlo
Susan Garavaglia, Ph.D., M.B.A.
Rose Healey
Tony Joseph
Mona Khalid, M.B.A.
Jeff May
Miriam Ryvkin, M.S.
Jodi Schreiber
Hannah Soh, R.Ph., M.B.A.
Richard Thornton
Jill Zelman
Additional contributors
Jennifer K. Benenson, Esq.
Beth Ann Bird, R.Ph., M.M.
Cindy Callahan
Kirk Cotham
Shannon E. Denison, M.A.
Woody Eisenberg, M.D.
Richard Faris, Ph.D., R.Ph.
Felix Frueh, Ph.D.
Lori Giardino
Laura Higgins
Mostafa Kamal
Lisa Lenzi, Pharm.D.
Jennifer Luddy
Barbara S. Menzel, M.P.H.
Justine Michelini, M.B.A.
Rosemary Perkins
Rod Scheck
Jeff Simek
Ann M. Smith, M.S.
Amy Steinkellner, Pharm.D.
Robert R. Verbrugge, Ph.D.
Stephen Wogen, M.H.A.
Lily Zariczny
All rights in the product names, trade names, or logos of all third-party products appearing in italics in this report, whether or not appearing with a
trademark symbol, belong exclusively to their respective owners.
Medco, Preferred Prescriptions, and Medco Therapeutic Resource Centers are registered trademarks and Medco making medicine smarter and Precision
Health Solutions are trademarks of Medco Health Solutions, Inc.
© 2010 Medco Health Solutions, Inc. All rights reserved.
100
> 2010
To our clients and friends:
We are pleased to share Medco’s 2010 Drug Trend Report highlighting 2009 data representing trends across our base
of clients. It’s clear that even as the rancor in Washington over healthcare reform ensued, Medco and our clients were
already planning for what’s next. Inside these pages, you’ll discover insights and solutions to help you prepare for the
challenges ahead.
Specialty trend maintained an upward climb throughout 2009, ending at 14.7%. Inflation in branded drugs accelerated
to an all-time high of 9.2%, while generic drug inflation remained flat at 0.3%. Despite these increases, Medco clients
realized an average drug trend of 3.7%. Notably, Medco clients with more than 50% mail-order pharmacy penetration
experienced virtually no trend increase (0.1% growth), while clients with less than 50% mail-order penetration
experienced a markedly higher trend increase rate of 5.3%.
Among the other insights revealed in this year’s report:
The generic dispensing rate increased 3.4% to 67.5% as Medco clients continued to embrace savings from generic
drugs. Within the next 3 years, a series of blockbuster drugs will become first-time generics.
Many former “adult” diseases are becoming more prevalent in children as obesity rates soar. Manufacturers are
filing patent extensions for pediatric indications to keep pace. Plans must develop disease prevention programs
and adjust benefit strategies to effectively manage chronic and complex conditions in ever-younger populations.
Central nervous system, endocrine and diabetes, and musculoskeletal and rheumatological drugs will account for
almost 50% of drug trend through 2012.
By fostering research partnerships with leading academic and clinical institutions, Medco remains committed to leading
the transition to precision medicine. The acquisition of DNA Direct, Inc., in early 2010 builds on this foundation—and
transforms research into actionable services designed to meet the expectations of our clients and patients.
This year’s report dissects the key factors that accelerated or moderated trend last year and examines the developments
that will shape trend moving forward. It also showcases many of the ways in which leaders are both innovating
and adapting their practices, policies, and programs to keep pace with the momentum of scientific discoveries and
opportunities associated with healthcare reform.
We encourage you to collaborate with your account manager to take advantage of what’s next.
Sincerely,
David B. Snow, Jr.
Chairman and CEO
Chief Medical Officer, President, Medco Research Institute
P.S. For additional copies of this report, please contact your Medco account representative. A PDF with supplemental
content is available for download at drugtrend.com.
2010 DRUG TREND REPORT
USE HORIZONTAL LOGO HERE
U
The papers, paper mills and printer utilized in the production of this 2010 Drug Trend Report are all
certified to Forest Stewardship Council (FSC) standards, which promote environmentally appropriate,
socially beneficial and economically viable management of the world’s forests.
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Drug Trend Report

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