3800 - Scrip

Transcription

3800 - Scrip

Stockwatch
Expert View
Can Biogen Find A Buyer
First-quarter earnings season got
underway and expectations were
not high however the first week of
announcements was not as bad as many
had feared (p22)
It’s easy for pharma and biotech to get
caught up in biomarkers and scientific
endpoints but a practical approach
is asking patients what they need or
want (p21)
It’s no secret that Biogen has been
facing some issues over the last year
but the latest rumors have the big
biotech selling off one of its lucrative
franchises (p4)
Scrip
29 April 2016
No. 3800
s cripintell ig e n c e .c om
Sir Andrew Witty
Witty On Pricing: Oncology
‘No Safe Haven’
Sukaina Virji [email protected]
“I
t’s time for industry and payers to
start thinking about different pricing
models, and it’s going to require some
transparency about what everything costs,”
said Sir Andrew Witty, speaking to Scrip on
18 April. “Lots of people will say pricing is not
an issue in oncology. It’s going to be an issue – it’s inevitable.”
Witty emphasized the importance of finding “sustainable” pricing models which deliver “a reasonable return for investment risk
but also makes sure that these medicines are
appropriately accessible to the people who
need them.” He believes there are two areas
where there is “clearly anxiety building up”
in terms of whether the current model will
continue to work: rare diseases and oncology. “These are the areas where I think there
needs to be a bit of innovative thinking.”
GSK is doing some of this innovative
thinking itself but Witty declined to go
into details “because it’s not something we
want to pre-lead on until we actually announce what we’re going to do, but we
certainly see there is a need for some innovation in pricing in this space.”
Oncology
At the moment GSK is in the “luxurious position” of not having to worry about pricing
Pharma intelligence | informa
issues in oncology, said Witty. GSK sold its
late stage oncology business to Novartis in
their mega asset swap deal which closed
last March. “But we will have to [worry
again] in the future. We’ve got more than a
dozen programs rolling through our pipelines in epigenetics and immune-oncology. It’s obvious to everyone that we’re going to have lots of combination therapies.”
These drugs currently cost in the region
of $100,000-plus, stated Witty, “and it’s not
impossible to start conceiving of people
having to take several of these for a long
period of time. That’s going to be a real issue with the payers. I don’t think oncology
is going to be a safe haven for ever.”
According to Witty, “You talk to any health
minister in the world, any payer in the US,
these people are worried about the potential aggregation of cost [of combination oncology medicines]. We have to try and figure out ways to make it work, because what
you don’t want is people get so stressed
about the risk of cost they then start to do
things which send a very negative signal to
R&D companies who then stop investing in
R&D. It’s going to take you a generation to
recover from that mistake. That’s what happened in antibiotics. We don’t want that
kind of problem [in oncology].”
How do you avoid that? “Get upfront and
start having a proper conversation about innovative pricing models,” suggested Witty.
Rare Disease
In early April GSK secured a positive opinion from the European Medicines Agency’s
advisory committee, the CHMP, for a gene
therapy to treat ADA-SCID (severe combined immunodeficiency due to adenosine
deaminase [ADA] deficiency).
Continued on page 7
in this issue
Novartis’
Entresto missed
the mark in the
first quarter of
the year
6
from the editor
AZ has entered into
research collaborations
to integrate genomics
into its drug discovery
and development
infrastructure
14
The British Generic
Manufacturers
Association has set
up a dedicated sector
group to promote
biosimilar medicines
17
COVER / Witty On Pricing: Oncology
‘No Safe Haven’
[email protected]
3Congrats, Your Vaccine Works; Now, Who Will Buy It?
Earlier this month we launched our new weekly
issue, and we promised that a new website would
soon follow. So it was that, in a flurry of sunshine
and snow showers (in London at least), our new
online platform went live this week. From your
feedback over the years, we know that those of us
who work on Scrip weren’t the only ones longing
for that day.
We hope you agree that the new Scrip site is a more
fitting home for all the exclusive intelligence and
analysis from our global team of journalists. We will
continue to report on our exclusive industry interactions, from C-suite interviews to conference insights
and from data crunching to expert opinion. The difference is it’s all hosted on a far cleaner, simpler site
with improved navigation, attractive formatting and
responsive design that lets you read Scrip on your
mobile or tablet as well as your desktop.
We’re going on a journey to discover great new ways
of presenting content, and we’re looking forward to
bringing you along. Keep that feedback coming (my
email address is above).
4Rumor Has It: Can Biogen Find A Buyer For
Hemophilia Drugs?
6Novartis’s Entresto Doesn’t Impress In 1Q; Orphan Drug
Fails In PhIII
7J&J Not Sweating Remicade Biosimilar Approval
8Celgene’s New Regime: Hugin And Alles Discuss Handing
Over The Reins
9Industry’s Rebate Arms Race: Securing Market Access
At A Cost
10 Business Bulletin
11 Barner Goes Out On A High As Boehringer Ingelheim
Returns To Growth
12 Interview: Revolution At GSK India
13 Sarepta Lashed Again; More Duchenne Market Doubt
14 AstraZeneca Teams Up With Venter, Sanger To Mine
Genomic Riches
15 Policy & Regulation Briefs
16 Will 2016 Bring US Biosimilar Reimbursement Clarity?
exclusive online content
1Q Earnings Preview: What To Expect From US,
EU Big Hitters
http://bit.ly/1Wls4eC
The slow drip of pharma industry earnings announcements
that began on April 19 with Roche and Johnson & Johnson will
turn into a veritable stream over the next couple of weeks. Scrip
takes a look at expectations around some of the main firms
due to report.
Video Interview: ‘More Out-Licensing Divestment
Expected In 2016,’ Says AZ’s Grady
http://bit.ly/1rwVM5p
AstraZeneca’s Shaun Grady discusses the company’s future and
tells that it remains committed to developing medicines across
small molecules, biologics, vaccines, protein engineering and
devices.
2 | Scrip intelligence | 29 April 2016
17 New Uk Industry Body To Promote Flagging Biosimilar
Market
18 AACR: Three Promising Anticancers From
Loxo Oncology, Ignyta And Beigene
20 R&D Bites
21 Expert View: Patient Registries Prove Value As Drug
Development Tools
22 Stockwatch: No Earnings Disappointments
Are The New Black
23 Pipeline Watch
24 Appointments
@ s cri pn e w s
/ s cri pi ntel l i genc e
/ s cri pi ntel l i g en ce
/ s cri pi ntel l i genc e
© Informa UK Ltd 2016
headline news
Congrats, Your Vaccine Works; Now, Who Will Buy It?
Donna Young [email protected]
J
Justifying Medical Countermeasures
Investment
Leading a panel discussion at the Maryland-Virginia-District of Columbia BioHealth Capital Region conference on April 19, Ripley Ballou, vice president of vaccines at GlaxoSmithKline PLC., said one of
the greatest challenges in developing products like the firm’s Ebola
vaccine, which it developed in collaboration with the US National
Institutes of Health (NIH), has been getting some sense of what the
supply and demand is going to be.
“You have to make these decisions very early in the development
cycle because it takes so long to build facilities and get them validated,” Ballou pointed out. “These are very risky decisions and it’s a
very tough issue to handle.”
“While everybody said, ‘Yes, we’re going to buy this vaccine,’” he
said, “when it finally came down to it, maybe they’ll buy 300,000
doses” for stockpiling.
“It’s hard to justify that kind of investment if that’s what we’re
talking about,” Ballou told attendees at the conference, which was
scripintelligence.com
hosted at AstraZeneca PLC.’s MedImmune Inc. campus in Gaithersburg, MD.
When GSK generally considers developing a vaccine, it looks first
at whether there’s an unmet medical need, if the R&D is technically
feasible, if conducting trials is clinically possible and whether there’s
a commercial strategy, he explained.
“If you can’t answer ‘yes’ to all four of those, it becomes a real challenge to prosecute the vaccine development,” Ballou declared. “It
can be done if one of those elements is missing if you have a strong
partner that can somehow compensate.”
Shutterstock: Alexander Raths
ohnson & Johnson Inc. and its collaborators, including Bavarian
Nordic AS, on April 19 published results of a Phase I trial showing
their AdVac/MVA-BN prime-boost Ebola vaccine regimen produced an antibody response in 100% of healthy volunteers, which
was sustained for eight months following immunization.
That’s good news. Except, it’s unclear now if the effort will pay off
in the end – meaning, whether the vaccine will make it through the
clinical testing and regulatory processes and there will be a buyer
for it now that the epidemic in West Africa, which killed more than
11,300 people, has subsided and all of the attention and some of
the US government funding has shifted to a new global threat: Zika.
Johan Van Hoof, global head of infectious diseases and vaccines
at J&J subsidiary Janssen Pharmaceuticals, acknowledged during
an April 19 media briefing that hundreds of millions of dollars already have been invested in the AdVac/MVA-BN prime-boost Ebola
vaccine, including $300m from the company, €100m from the Innovative Medicines Initiative, a joint venture of the European Union
and the European Federation of Pharmaceutical Industries and
Associations, and about $50m from the US Biomedical Advanced
Research and Development Authority.
But Van Hoof insisted the reason J&J “stepped into” the race for
an Ebola vaccine is because the company believed its technology
platforms and manufacturing capabilities “could be part of the solution and contribute” and not as a moneymaking venture.
“We did not have commercial intentions when we actually started this initiative, which we felt was being part of our corporate responsibility,” Van Hoof told reporters.
He argued that while it’s necessary to address Zika, “we should
not underestimate the work that needs to be done for Ebola and we
should not become complacent with regards to the Ebola threat” –
pointing out there’s still some small outbreaks erupting in West Africa.
“Regulators also have the opinion we should continue the work,
bring the data together to get the products approved and make
them available to the population,” Van Hoof said.
James Jackson, chief scientific officer at Gaithersburg, MD-based
Emergent Biosolutions Inc., said firms like his that are developing
medical countermeasures (MCM), in which there isn’t a commercial
market, must not only ask whether there’s a strong government
partner for the development of those vaccines, such as the company’s anthrax product BioThrax, “but are they committed to procurement in the long term.”
“From a business perspective, what is our incentive, how do we
justify that return on investment for continuing to develop and
manufacture new anthrax vaccines if there isn’t going to be some
sort of business justification at the end?” Jackson asked.
Sustained Funding
Several on the panel noted there must be sustained government
funding for their firms to be able to make the business case to their
investors to keep pursuing MCM vaccines and drugs.
The Global Health Technologies Coalition (GHTC), a group of 27
nonprofits, funded in part by the Bill & Melinda Gates Foundation,
warned in a new report on April 19 that stagnant US funding for
lifesaving tools against infectious disease threats like Ebola and Zika
puts the nation and the world at large at “serious risk.”
The group called on Congress to significantly boost funding levels
for several US agencies that provide grants for global health programs or research and development or oversee regulatory activities.
They urged lawmakers to appropriate $3.73bn for the US Agency
for International Development’s global health programs, $6.2bn or
the State Department’s global health programs, $34.5bn for the
NIH, $1.09bn for the Centers for Disease Control and Prevention’s
National Center for Emerging and Zoonotic Infectious Diseases and
Center for Global Health and $2.9bn for the FDA.
29 April 2016 | Scrip intelligence | 3
headline news
Rumor Has It: Can Biogen Find A Buyer For
Hemophilia Drugs?
Shutterstock: SebGross
Lisa LaMotta [email protected]
I
t’s no secret that Biogen Inc. has been
facing some issues over the last year as
shares have dropped, management has
exited and the company has made staffing cuts, but the latest rumors have the
big biotech selling off one of its lucrative
franchises. The move would not only be a
drastic shift for the company, but begs the
question: who would buy?
In rumors that began to surface in the
media earlier in April, unnamed sources say
the company has hired the services of an
investment bank to explore the potential
sale of its hemophilia franchise.
The move is a complete about-face
from the message the company has been
spouting for the last year, even as turmoil
has reigned at Biogen: that it is in the
market for mergers and acquisitions. The
company is likely to face questions about
its M&A strategy and the potential sale of
its hemophilia assets when it reports first
quarter earnings on April 21, but CEO
George Scangos could be heard as recently
as January telling attendees at the annual
J.P. Morgan Healthcare Conference that
Biogen is interested in deals.
“We will continue to do business development. There’s no question about that,
right, and now if the current climate for
the value of biotech companies continues,
it just makes the opportunities continue,
it just makes the opportunities easier to
come by,” Scangos said at the conference.
Scangos also touched upon the hemophilia business while speaking at J.P.
Morgan, noting that Biogen’s portfolio
represents “the first true innovations in the
treatment of hemophilia in a long time.”
“We believe they have the potential to
capture a substantial part of this market. It
is a $7bn market and we believe we have
the products that can help us to capture a
significant part of that,” he added.
With that sort of potential, it seems odd
that Biogen would want to ditch the products now – but the hemophilia franchise
has always been a little outside its area of
expertise.
Square Peg, Round Hole
Through a series of licenses and acquisitions, Biogen got the rights to its two hemophilia drugs in 2006 from Swedish Orphan Biovitrum (SOBI). Yet, the company
didn’t start promoting the potential of
Eloctate and Alprolix (which were both approved by FDA in 2014) until Scangos took
over the helm of the company in 2010.
The CEO began touting the prospects of
the franchise and outwardly talking about
hemophilia as a cornerstone of Biogen’s
future.
While Biogen was deeply involved in the
development of the two long-acting hemophilia drugs, they are distinctly outside
its area of expertise in neurodegenerative
diseases. Biogen is most well-known for its
multiple sclerosis treatments, from which
it derives more than three-quarters of its
revenues. Its pipeline is heavily weighted
toward this area as well, with its Phase III
candidates including its fifth treatment
for MS, ocrelizumab, as well as the closely
watched aducanumab for Alzheimer’s disease and nusinersen for spinal muscular
atrophy (SMA).
With the odd fit, analysts wouldn’t be
disappointed to see Biogen divest the assets and bring a healthy chunk of cash.
Leerink Swann analyst Geoffrey Porges values the drugs at $5.9bn.
make just a few key drugs, including Bayer
AG, Baxalta Inc. and Novo Nordisk AS. Patients have long had the option of treating
the disease prophylactically or only taking
drugs when they experience a life-threatening bleed in an on-demand regimen.
Yet, that treatment paradigm has been
changing and the market was recently disrupted by long-acting technology that is
allowing patients to go from preventative
infusions taken daily to preventative infusions taken every three to four days – this is
where Biogen entered the market. Hemophilia patients have been loath to switch
their medications due to safety issues that
cropped up in the 1980s and 90s, making these patients particularly brand loyal.
Yet, it seems the tides are turning as better
treatment options become available.
The hemophilia market is going to continue to evolve over the next few years as
that same technology enables companies
to bring forward treatments that are even
longer-acting. There are also a handful
of gene therapies that are earlier in the
pipeline that could change the treatment
paradigm completely, allowing patients to
get a single infusion once or twice per year,
although those are still several years out.
Datamonitor Healthcare estimates that
the worldwide hemophilia market will
grow from $10.5bn in 2014 to $12.9bn
in 2023, driven by on-demand patients
switching to preventative treatment as
long-acting therapies take over more of the
market. Due to this, Datamonitor analysts
believe that Biogen is strongly positioned
with its two currently marketed therapies
to take over a large share of the market.
The small number of players in the hemophilia market makes the potential number of buyers for Biogen’s products very
slim. Unfortunately for Biogen, it’s not the
only hemophilia player going through a
transition.
CLICK
So Who’s Buying?
The hemophilia market has been long dominated by a small number of companies who
Read full story at:
http://bit.ly/23UyyqK
headline news
OBESITY
Obesity is one of the most prevalent diseases in the US, according to CDC, which
estimates that about one-third of Americans, or 76 million adults, are obese.
Obesity leads to other chronic conditions like diabetes, heart disease and some
cancers. Yet, patients and physicians have been slow to turn to drugs for treatment.
BY THE
2015 BRANDED OBESITY DRUG SALES2
NUMBERS
$56.4m QSYMIA $53m CONTRAVE
$42m BELVIQ $38m SAXENDA
NUMBER OF SALES
REPS IN THE FIELD1
MARKET SHARE FOR US BRANDED
ANTIOBESITY DRUGS3
50 QSYMIA
230 BELVIQ
900 CONTRAVE
■ CONTRAVE
■ BELVIQ
■ QSYMIA
■ SAXENDA
$56.4mReducing to 160
in September
26%
27%
7%
41%
DRUGS IN THE PIPELINE4
0 drugs in Phase III 8 drugs in Phase II 8 drugs in Phase I
DIET DRUG TIMELINE5
Phentermine
enters the market
1950s
Redux (dexfenfluramine)
marketed by Wyeth
EARLY
1900s
APRIL
SEPTEMBER
SEPTEMBER
1996
Fen-Phen
(fenfluramine and phentermine)
combo becomes popular
appetite suppressant
Xenical (orlistat) approval
1999
1997
All forms of fenfluramine
pulled from market due
to cardiovascular safety issues
JUNE
JULY
2007
Orlistat (Xenical)
approved
for OTC use and
sold as Alli
JUNE
2015
2014
2013
2012
2012
2010
Saxenda gains
FDA approval
Contrave
approved
Belviq finally launched
Qsymia approved
by FDA
Belviq approved,
but not launched due
to classification by DEA
Xenical/Alli found
to cause severe
liver injury;
label revised
Sources: 1Companies; 2Companies/analysts; 3IMS Health (as of March 15); 4BioMedTracker; 5Drug labels, FDA archives
headline news
Novartis’s Entresto Doesn’t Impress In 1Q; Orphan
Drug Fails In PhIII
Lucie Ellis [email protected]
Shutterstock: Pincasso
N
ovartis AG’s newly launched heart
failure drug Entresto (valsartan/sacubitril), which has been dubbed
the company’s next blockbuster product,
missed the mark in the first quarter of the
year, posting sales more than $10m below
analyst forecasts.
In its 1Q 2016 earnings report Novartis,
for the first time, gave a sales projection figure for Entresto for this full year, predicting
$200m for the drug – a big drop from analysts’ $300-400m expectations. And in the
first quarter the drug saw sales reach just
$17m, a far cry from the anticipated $30m
for the period.
Novartis said on its April 21 earnings call
that though Entresto, a single molecule
comprising molecular moieties of valsartan
and NEP inhibitor prodrug AHU377, saw a
“modest” first quarter; it still has its eye on
a peak sales figure of $5bn for the drug.
Though when this peak moment will arrive
has not been placed on a timeline.
CEO of Novartis’ pharma division, David
Epstein, noted that sales for the drug, which
was approved for the treatment of congestive heart failure in July 2015, would be driven by European and other ex-US markets.
Epstein said Entresto sales this year are
primarily in the three markets: Switzerland,
Germany and France. “A number of countries
will provide reimbursement starting in 3Q
and then 4Q… so it should be a nice growth
driver for Entresto as we start 2017,” he said.
Novartis is not the only one struggling in
the heart disease space though; Sanofi and
Amgen Inc. have also seen slow gains for
their PCSK9 cholesterol-fighting products,
Praluent (alirocumab; also approved in July
2015) and Repatha (evolocumab; approved
in August 2015). However, the US list price
for Entresto is around $4,500 a year, while
the PCSK9 drugs cost about $14,000.
Epstein explained in Novartis’s 1Q call
that the company was receiving some
pushback from cardiologists against prescribing Entresto. Doctors say, “I want to follow the label exactly, or they’ll say I want to
wait for guidelines. But these are all excuses
because there is still underlying discomfort
at moving patients [onto Entresto] because
we haven’t really, in my opinion, held their
hand enough and supported them,” Epstein
said. He added that doctors were also reluctant because “the reimbursers made it so
difficult for them to initially try the drug.”
1Q Numbers
Dr. Tim Anderson, global pharmaceuticals analyst at Sanford C. Bernstein LLC.,
noted that overall Novartis had a reasonable first quarter, but its earnings for the
period are “indicative of the headwinds it
will face in 2016.”
sIMB Drug Fails In PhIII
Novartis also disclosed in its 1Q report that
investigational drug bimagrumab failed to
meet its primary endpoint in a pivotal Phase
IIb/III trial for the treatment of sporadic inclusion body myositis (sIMB). The company
said it was “evaluating the complete dataset
to inform decisions regarding ongoing de-
velopment of bimagrumab.” The drug is also
in development for the treatment of musculoskeletal conditions and cachexia.
The sIMB program, which had been
granted an orphan drug designation and
breakthrough therapy status in the US, was
considered high risk and there are only
two other drugs in development for this
disease. Milo Biotechnology is developing
AAV1-FS344, currently in Phase I/II studies;
and Sanofi has Campath, which is currently
being studied in an investigator initiated
trial. All three drugs have independent targets, so Novartis’s Phase III failure is unlikely
to impact the other two ongoing trials.
SIMB is an inflammatory muscle disorder,
with slowly progressive weakness and wasting of distal and proximal muscles, most noticeable in the muscles of the arms and legs.
There appears to be both autoimmune and
degenerative processes going on and sIMB
is thought to be the most common acquired
myopathy in patients over 50 years old.
1Q And Numbers
1Q 2016 (US $)
1Q 2015 (US $)
Net Sales
11.6bn
11.9bn
Operating Income
2.5bn
2.8bn
Net Income
2bn
2.3bn
EPS
0.85
0.96
Pharma Sales
7.7bn
7.1bn
Sandoz Unit Net Sales
2.4bn
2.2bn
Alcon Unit Net Sales
1.4bn
2.6bn
headline news
J&J Not Sweating Remicade
Biosimilar Approval
Jessica Merrill [email protected]
J
ohnson & Johnson Inc. does not expect a biosimilar rival to its blockbuster
tumor necrosis factor (TNF) inhibitor
Remicade (infliximab) will launch in the US
this year, despite the FDA approval of Celltrion Inc.’s Inflectra (infliximab-dyyb) April 5,
and it remains comfortable with the growth
outlook for pharmaceuticals.
“We don’t expect biosimilar competition
in 2016,” chief financial officer Dominic Caruso said during the company’s first quarter
sales and earnings call April 19. “We have
several patents that we intend to defend.”
J&J does not expect
significant pricing pressure
for new medicines in
immunology even if a
biosimilar anti-TNF reaches
the market
Caruso pointed to Remicade’s patent
No. 6,284,471, which expires in September
2018, and another patent that extends to
2027 as support for keeping a biosimilar off
the market for now. But the enforceability
of the patent expiring in 2018 is uncertain
after the Patent and Trademark Office (PTO)
found the patent to be invalid in a reexamination proceeding. The decision is on appeal before the PTO’s Patent, Trial and Appeal Board (PTAB).
Celltrion’s partner on the US launch of
Inflectra, Pfizer Inc., has said it is preparing
to launch the biosimilar this year, though
acknowledged it could be delayed. Inflectra is only the second biosimilar approved
by FDA.
Remicade is J&J’s top-selling drug; it generated $1.78bn worldwide in the first quarter of 2016. Remicade generated $1.21bn
in the US, up 14.8% during the quarter. Biosimilar versions of Remicade have already
launched in Europe, where the drug is marketed by Merck & Co. Inc.
Despite the threat to its top revenue
generator, Caruso said J&J is “comfortable”
with the company’s growth outlook for the
pharmaceutical segment regardless of the
launch timeline of Inflectra.
“Overall, the immunology franchise of
Johnson & Johnson is very strong because
it’s not just about Remicade,” he said.
The franchise also includes Simponi (golimumab) and Stelara (ustekinumab), which
generated $390m and $735m in the first
quarter, respectively. J&J expects to launch
new drugs in immunology too: the antiIL-23 antibody guselkumab for psoriasis
and the anti-IL-6 antibody sirukumab for
rheumatoid arthritis.
Caruso said J&J does not expect significant pricing pressure for new innovative
medicines in immunology even if a biosimilar anti-TNF reaches the market.
“Innovative products that have a significant impact on unmet medical need – in
this case it would be those patients that are
not otherwise responding to, for example,
TNF therapy, our view is that … the products will still continue to be valued,” he said.
J&J’s Pharmaceutical unit had a strong
first quarter, with worldwide sales up 5.9%
to $8.19bn, driven by growth in immunology, the SGLT-inhibitor Invokana/Invokamet (canagliflozin) for type 2 diabetes, the
oral anticoagulant Xarelto (rivaroxaban),
as well as by strong launches in oncology
with Imbruvica (ibrutinib) for certain B-cell
malignancies and Darzalex (daratumumab)
for multiple myeloma.
Darzalex, which was approved by FDA
in November, contributed over 2% to
US pharmaceutical growth, Caruso said,
though the company did not break out
sales. Darzalex is a first-in-class anti-CD38
monoclonal antibody; it was approved as
a monotherapy in heavily treated patients
following at least three lines of therapy.
Imbruvica generated $261m worldwide
in the first quarter, up from $116m in the
year-ago quarter. Imbruvica, partnered with
AbbVie Inc., secured a new indication from
FDA in March for first-line use in patients
with chronic lymphocytic leukemia.
Continued from cover
“Strimvelis is a one-time treatment,” GSK
told Scrip at the time. “Gene therapy is
highly individualized and there is no other
medicine against which Strimvelis can
be compared.” GSK is exploring “different
pricing options, including both traditional
reimbursement routes as well as more innovative approaches.”
‘It’s time for industry
and payers to start
thinking about different
pricing models, and it’s
going to require some
transparency about what
everything costs’
On Strimvelis, Witty said: “If you look at
something like ADA-SCID then probably
we’re talking, thank goodness, of tens of patients being the beneficiary of that drug.” But
the development program cost hundreds of
millions of dollars, he noted. “If people want
ultra-rare disease medicines, and I think the
world does, we’re going to have to think creatively about how we manage that.”
Antibiotics
There is a clearly an issue with antibiotics
“where you’ve got this very sensible logic
of ‘we want powerful antibiotics but if we
have them we don’t want to use them because we want to keep them for resistant
organisms.’”
This logic is “completely appropriate,”
the CEO believes, but as a consequence,
“If you don’t think your drug is going to
be used very much then you’re going to
charge a high price because you don’t
think the volume is going to be very high.
If you charge a high price, then it’s not going to be reimbursed. You’re into a completely catch 22 scenario. It just needs rethinking. It’s completely solvable, we just
need to rethink it.”
Antibiotics are “the most acute obvious
thing that needs to be sorted out,” stated
Witty, and fortunately “there’re lots of people
working on that.”
headline news
Celgene’s New Regime:
Hugin And Alles Discuss
Handing Over The Reins
Lucie Ellis [email protected]
Mark Alles has been in his first pharma chief executive role for
six weeks, after stepping into former Celgene Corp. leader Bob
Hugin’s shoes in March. While Alles has been with the company
for 12 years and in the pharma industry for three decades he
brings new skills to the top spot at Celgene and a keen eye for
keeping science at the fore of his corporate decision making.
A
lles and Hugin sat down with Scrip’s Lucie Ellis at Celgene’s
recent innovation summit, held at its European headquarters
in Boudry, Switzerland, to discuss transitioning leadership at
the company, why they are still represent a unified front, and how as
CEO and chair they will preserve Celgene’s specialty pharma culture
even as the business continues to grow.
The ecosystem we are a part of is
not just about Celgene, it’s about
how you work with governments
around the world. We have to think
about how we can participate and
customize our involvement with
governments globally
Bob Hugin
Mark Alles
and strengthen the leadership team and I am optimistic that is
going to happen.
LE: You will remain as chair of Celgene’s board, what will be your
focus in this role?
BH: First and foremost Mark is the chief executive and my job is
to help him be successful in driving the company forward. I have
been involved in a lot of external arrangements that have helped
Celgene in its business development planning and execution and
as chair I will be focused on ensuring the board of management
crafts the right business plan going forward. I look forward to being a good partner to Mark, to see that he and the company is as
successful as possible.
LE: What do you want to see Celgene achieve in the future?
BH: I want to see our mission for improving human health stay
robust. I want to see us stay bold and have the type of culture that
is focused on the patient needs. This provides our teams the environment to do great things. The opportunity for people at Celgene to be impactful is what we want to maintain and advance.
LE: How do you maintain that kind of culture?
Lucie Ellis: Bob, why did you step down as CEO this year and
was it a difficult decision to make?
Bob Hugin: Difficult decisions are always the ones that need
to be thoughtfully made and I considered this decision for some
time. The logic behind it is not so much me stepping down but
it’s about elevating others from within the company. Celgene has
built what I believe is one of the most high-potential pipelines in
the industry, alongside this the company has thought a lot about
developing people to ensure the maximum number of people
can have maximum impact on the organization. We are fortunate
at the company to have a lot of good people and the last thing
we wanted to do was create a succession plan, like other businesses do, where they start with five to 10 people and end up
with just one, as people leave over time. My thinking has always
been the more people we have who are successful, the better
the company is for it. I intend to carry on in a very active role in
Celgene moving forwards and chair of the board is the fourth title
I have had now. I think I have managed to have a strong impact
though with every title I have held, but I really wanted to expand
BH: When I think about leadership the words that come to me
are humble and service. The more influential you get, the greater
opportunity you have to serve others effectively. Success doesn’t
lead to complacency it gives you opportunity to have more of
impact. I maintained this ambitious culture at Celgene by ensuring I walked the walk. But Mark can tell you more about this
moving forwards…
Mark Alles: The ecosystem we are a part of is not just about Celgene, it’s about how you work with governments around the world.
We have to think about how we can participate and customize our
involvement with governments globally. We have to have flexibility. A
lot of technology companies talk about how rigorous their hiring process is, like Google and Microsoft, at Celgene we understand that your
long term success collates back to the culture of the company and
who you have hired.
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headline news
Industry’s Rebate Arms Race:
Securing Market Access At A Cost
Jessica Merrill [email protected]
R
ebates have become industry’s go-to
for securing market access for drugs in
competitive therapeutic areas in the
US. But as payers push back, competitive
rebating is intensifying and eating into the
bottom line.
The drug industry is in a rebate arms race
– at least in some highly competitive therapeutic areas like cardiovascular disease, respiratory disease and diabetes – with rivals
offering increasingly deep discounts to secure prime real estate on formularies.
Industry’s rebate practices are among
the most closely guarded secrets in the
pharmaceutical industry, so finding out
precisely what kind of discounts companies are offering for their products is next
to impossible.
The issue of rebates also plays directly
into the growing controversy over drug
pricing. Without knowing the amount of
a rebate, it’s hard to understand the actual cost of a drug (the list price minus
rebates and other discounts), leaving the
public in the dark about the actual cost
of therapy.
In the US, some rebates are mandated
under state and federal programs, while
others are negotiated directly with private
insurers and pharmacy benefit managers
in exchange for formulary access. Those
contracted payments are the ones that are
cloaked in secrecy.
But what is clear is that industry spends
billions of dollars each year on rebates, an
expense that cuts into the bottom line, and
spending on rebates as a percent of gross
US pharma sales is increasing.
Rebates as a percent of gross US pharma
sales increased by 14 percentage points
over seven years on average, from 2007 to
2014, according to a new report by Bain &
Co. Rebates on average were 19% of gross
US pharma sales across the industry in
2007, versus 33% in 2014.
Even more notably, the amount some
companies are spending on rebates is approaching or surpassing 50% of gross sales.
AstraZeneca PLC spent 57% of gross US
pharma sales on rebates, while Novo Nor-
disk AS and Sanofi spent 47% and 45%, respectively, according to the report. (AstraZeneca, however, said it spent 51% of gross
US pharma sales on rebates in 2014.)
“In addition to noticing overall increases
in level of rebates over the last five years,
we have noticed there are other supplemental tactics being taken like more aggressive copays, which although it’s not
reflective in the same way as rebates in
terms of gross to net, it’s still a supplemental cost,” Bain & Co. partner Roger Sawhney, one of the authors of the report, said
in an interview.
“Our real focus is on how can companies
think about this problem and prevent a
race to the bottom, which is to say a cycle
of rebating where they completely destroy
their ultimate profitability,” he added.
Some of the hit from rebates is offset by
price increases, which drug makers generally take on drugs annually if not more often. But efforts by legislators and the general public to reign in healthcare spending
have put a spotlight on drug pricing, and
especially aggressive price increases, which
could hinder industry’s ability to take big
increases.
A report released April 14 by IMS Health
further highlighted the trend. Discounts,
rebates and other price concessions to
payers offset price increases for patentprotected branded drugs by 77%-81% in
2015, according to IMS. Although list prices
increased 12.4% in 2015, net prices grew
only 2.8% on average for the year.
Bernstein research analyst Tim Anderson
highlighted the IMS report in a same-day
research note, pointing out that the data
“implies that if the drug industry were to
moderate the annual price increases it
takes – for fear of further scrutiny – then
net US drug pricing might accordingly slip
into negative y/y territory, mirroring the
gradual price erosion that occurs in almost
all other developed countries outside of
the US.”
“However, it remains to be seen whether
the drug industry can actually afford to
stop taking its price increases,” he added.
High Stakes Wagers
In Primary Care
The most cutthroat rebating is taking
place in competitive primary care therapeutic categories like cardiovascular disease, respiratory disease and diabetes.
It’s not surprising then that AstraZeneca,
Novo Nordisk and Sanofi – all big diabetes players – are among the companies
spending the most on rebates as a percent
of US pharma revenues.
In these categories there are often
multiple drugs on the market that work
through the same mechanism of action,
which means there is more wiggle room
for payers to pit competitors against
each other bidding for access. As payers
have consolidated, their influence has
grown; six pharmacy benefit managers
now represent 90% of covered lives in
the US, Bain said.
That means that especially in the markets with the most competition, there is
considerable pressure on manufacturers
to make accommodations. “Several AstraZeneca products are in highly competitive
markets,” US President Paul Hudson said
in an email. “In order to make these medicines available to patients, we offer payers
rebates and discounts.”
Payers have increasingly excluded certain drugs from formularies altogether as
a way to negotiate the best price. Drug
makers that have been burned by formulary exclusions haven’t taken the same
chance the second time around. GlaxoSmithKline PLC’s market-leading asthma
drug Advair Diskus (fluticasone/salmeterol) was excluded from Express Scripts
Holding Co.’s formulary in 2014, and sales
of the drug nose-dived as a result. The
company offered deeper discounts in
2015 and Advair was returned to the formulary, though the company took a hit
on price.
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business bulletin
Recipharm Builds Global
Scale With Kemwell Buy
Recipharm AB is acquiring Kemwell’s
pharmaceutical contract development
and manufacturing (CDMO) businesses for about SEK1.7bn ($206m)
– a transaction that will give the Swedish firm an operational presence in the
US and also builds on its position in
emerging markets. The deal entails two
separate agreements and covers Kemwell’s US, Swedish and Indian operations. The acquired businesses notched
2015 preliminary net sales of about
SEK745m, which corresponds to 22%
of Recipharm’s 2015 net sales. The acquisitions are expected to be accretive
to EBITDA [earnings before interest,
taxes, depreciation and amortization]
margins from 2016. Recipharm will
fork out approximately SEK693m for
the US and Swedish operations payable
to sellers, Kemfin Holdings Private Ltd
and, as regards the Swedish operations,
a minor additional owner, with about
SEK243m in cash as well as through
an issue in kind of class B shares in Recipharm corresponding to a value of
SEK450m. The India deal will entail a
consideration of SEK982m payable to
the Bagaria family and certain related
parties. Thomas Eldered, CEO of Recipharm, said that the transactions represented a significant step in the consolidation of the CDMO industry and
the transformation of Recipharm into
a global leader. He expects to use the
US footprint to further penetrate the
market, while the business in Sweden
provides the firm with several opportunities for synergies.
Bangladesh Market On
Uptrend
Half a dozen players, community-based
diagnosis and patient support efforts,
and an inflow of treatment seekers from
abroad keen to access cut-price drugs in
the country – this probably summarizes
the current state of play in Bangladesh’s
market for sofosbuvir. The early gains in
the hepatitis C segment come alongside
Biogen Backs Down From M&A
Biogen Inc. wouldn’t acknowledge rumors that it plans to sell its hemophilia business, but CEO George Scangos told analysts during a first quarter earnings call that the big biotech will be focusing on “cost control” and
keeping its head down. “For the remainder of the year, we are focused on
three areas: careful control of our costs, maximizing our revenues, and rapidly advancing the pipeline. The cost reduction actions that we took last
year resulted in a meaningful increase in earnings this quarter and as we
move through the year, we will continue to focus on cost control to do all
that we can to concentrate our resources on the activities that we believe
will add the greatest value,” he said on the April 21 call. The executive’s
comments will likely mean that M&A is not in the cards for Biogen as it focuses more on its pipeline and tries to turn things around as its commercial
products languish. While Scangos would not entertain speculation about
the sale of the hemophilia business, don’t expect a deal anytime soon – it
may be tough for Biogen to find a buyer.
expectations of sustained robust growth
in the overall Bangladesh pharma market buoyed by, among other factors, socioeconomic progress and better access
in the South Asian nation. Last year,
local Bangladesh firms led by Incepta
Pharmaceuticals and Beximco Pharmaceuticals launched cut-price versions of
Gilead’s hepatitis C treatments Sovaldi
(sofosbuvir) and Harvoni (the fixeddose combination of ledipasvir and sofosbuvir). “These drugs are available in
Bangladesh at the lowest possible price
(over 99% cheaper than the originator
brands). Both Beximco and Incepta have
received a good response, especially from
overseas patients who do not have access
to generic copies,” Shawkat Haider, general manager (business development)
at Beximco, told Scrip. Haider indicated
that most of the foreign patients from
Asia, Eastern Europe and the Middle
East came to Bangladesh seeking treatment with generic Harvoni in particular,
which Beximco and Incepta launched
last year ahead of Indian firms. Six manufacturers have launched sofosbuvir in
Bangladesh since, but only Beximco and
Incepta offer both sofosbuvir and the
sofosbuvir+ledipasvir combination. The
domestic market for these direct-acting
antivirals in 2015 (not the full year) has
been estimated at more than Tk200m
($2.6m) including foreign patients treated in the country.
Dull March Growth For
Indian Market
The Indian pharmaceutical market reported its lowest growth in FY16 during
the month of March, disrupted to some
extent by regulatory and price-related
actions. However, a clutch of domestic
and foreign firms outpaced the market
sharply. Data from AIOCD AWACS,
a market research agency that tracks
retail sales, indicated that the Indian
market grew by 6.4% in March, around
half that of the previous month. March
saw a decline in volumes, though this
was offset to some extent by price increases and new introductions. The Indian market was valued at INR79.17bn
($1.2bn) in March. Overall growth for
the quarter ended March 2016 was lower at 9.3% against 16.8% for the same
period last year. For the 12-months to
March 2016, the Indian market was
valued at around INR984.14bn. Last
month, India’s ministry of health and
family welfare banned, with immediate effect, 344 fixed dose combinations
deemed likely to involve “risk to human
beings” and where safer alternatives are
available. Several companies have challenged the order and hearings in these
cases are expected to resume next week.
headline news
Barner Goes Out On A High As Boehringer Ingelheim
Returns To Growth
Eleanor Malone [email protected]
P
rofessor Dr Andreas Barner, the outgoing chief of Boehringer Ingelheim,
was able to report a return to growth
for the family-owned German company
in 2015 at his final annual conference. The
group was boosted by diabetes sales under
its partnership with Eli Lilly & Co - as well as
by the strength of the dollar. The company
reports in euros but books nearly 40% of
its sales in the US. With currency effects
stripped out, the sales were up by a more
modest 4.1% versus the 11.1% as reported.
The company’s anticoagulant Pradaxa
(dabigatran) is still failing to meet previous
expectations, though. Barner was bullish
about its prospects, citing the US and European approval in the second half of 2015 of
the reversal agent Praxbind (idarucizumab),
and the fact that 30-35% of atrial fibrillation
patients are still not on an anticoagulant, as
likely drivers of demand this year. Director of
pharma marketing and sales Allan Hillgrove
said the company had “really seen a change”
in Pradaxa new prescription trends where
Praxbind has been launched. Hillgrove said
there would be growth in prescriptions and
in overall sales for the product in 2016.
Management would not reveal sales of
Jardiance (empagliflozin), the sodium glucose cotransporter 2 (SGLT2) inhibitor for
type 2 diabetes which was launched in 2014
in the US and Europe, and which Hillgrove
said “will be a multi-blockbuster for sure.”
The product was boosted by the EMPAREG OUTCOME trial results last year which
showed an unexpectedly high cardiovascular death risk reduction in diabetics at high
risk of cardiovascular events. Boehringer
also announced during the conference that
it and Lilly plan to launch two trials of Jardiance as a treatment for chronic heart failure
in both diabetics and non-diabetics.
Restructuring
In July, current finance chief Hubertus von
Baumbach will assume the leadership of
the company, coinciding with the formal
launch of a new structure for its prescription medicine business, which accounts for
72% of sales.
Professor Dr Andreas Barner
The business will be divided into an innovation unit, covering R&D up to clinical proof
of concept (i.e., Phase Ib/IIa), to be led by R&D
chief Dr Michel Pairet and including around
4,000 staff, and a prescription medicines
business unit led by Hillgrove. The change
was motivated in part by a desire to place
more focus on the customer as opposed to
the prior “functional focus [which] worked
very well in the past,” Hillgrove explained.
The firm is setting up a customer focus
group to look at subjects like market access, epidemiology and real-world data
and focus increasingly on proving the value of its products not just to patients but
also their economic value. One hope is that
real-world data could be harnessed to improve the efficiency of post-marketing trials, he said. He also said the firm was open
to risk sharing and was in talks with several
bodies in the US and the EU about “how to
reward the value” of Pradaxa. The approach
will apply to other products too.
From an early-stage R&D point of view,
Pairet said the priorities were to build on
the company’s existing therapeutic areas
of strength; “create synergies and build
bridges,” and to capture emerging science
beyond Boehringer’s current core therapeutic areas. External partnering is a big part of
his unit’s activities, and he highlighted programs as diverse as non-alcoholic steatohepatitis (NASH), optogenetics in psychiatry
and cancer vaccines as cases in point. The
unit has identified regenerative medicine,
the microbiome, gene therapy and hearing
loss as promising to explore. Conversely, it
has “paused” its research into disease-modifying Alzheimer’s treatment as it did not feel
it had anything to add to the approaches
being taken by others in the field.
In earlier oncology R&D, Boehringer is working on the principle that immune checkpoint
inhibitors will need to be combined with
cancer vaccines in certain cancers. It is working on its own checkpoint inhibitors and is
collaborating with academia/small biotechs
on next generation checkpoint inhibitors. In
cancer vaccines, it has a deal with Curevac
for the latter’s RNA cancer immmunotherapy
candidate CV9202 in lung cancer.
Sanofi Business Swap
Barner indicated that he is hoping to conclude the previously announced business
unit swap with Sanofi, whereby Boehringer bulks up in animal health by acquiring Sanofi’s business but offloads its
consumer health business to the French
group, before June 30 when he departs.
Nevertheless, he conceded that it would
depend on approval by the US FTC and
EU Commission. The €4.7bn planned payment to Sanofi, coupled with Boehringer’s
determination to retain sufficient financial
funds to protect its independence, reduce
the likelihood of significant deal making
this year.
No More Big Partnerships
Boehringer is hoping to make a success of
its recently announced partnership with
AbbVie for its anti-IL-23 compounds in autoimmune conditions, and is already reaping the benefits of its commercial partnership with Lilly in diabetes. However, don’t
expect any more large partnerships: “We
cannot carry more,” said Barner.
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interview
Revolution At GSK India
Anju Ghangurde [email protected]
B
race for GSK India’s new avatar. The
British multinational is revamping its
business model in India and donning
a new approach to create, deliver and capture value via a “one team” effort as it strives
to emerge as the fastest growing pharma
multinational in the country by 2020.
Cross functional “excellence teams,” a multichannel approach to reduce “information
asymmetry” for customers, calibrating prices
to improve access and penetrating deeper
into middle and rural India are some of the
core components of the ongoing effort.
“Given the new environment in India, we
need to re-engineer the business model in a
way that we are able to maintain margins but
at the same time deliver value of relevance to
our stakeholders – physicians, hospitals and
the government. The value creation that we
are looking at has to be different from what
we’ve done in the past,” Annaswamy Vaidheesh, GlaxoSmithKline Pharmaceuticals’ vice
president South Asia and managing director
India, told Scrip in an exclusive interaction.
Market equilibrium in India has, over the
past few years, been significantly impacted
by an “aggressive ecosystem” by way of
India’s national list of essential medicines
(typically subject to price caps), escalating expectations on quality standards and regulatory changes. GSK India, once the top ranked
company in India, is currently at sixth position
as per IMS March 2016 MAT (moving annual
total) data.
The GSK India boss touched upon a string
of initiatives underway at the company including using digital technology to reach out
to customers and taking the concept of “trust
in science” to its stakeholders.
The days of medical reps alone delivering messages through visual aids and standard information are passé and GSK India is
now building on the use of multichannel
approaches, webinars etc. to reach more
physicians.
“We want to reduce the so-called information asymmetry by using this multichannel. With this, the ability to create value for
customers goes up significantly,” Vaidheesh
added.
Scrip had previously reported how GSK
India had rolled out a digital initiative in the
CNS segment, with an expert digital meeting
in the area of bipolar disorder in the Indian
perspective. On building on the “trust in science” concept, the GSK India boss expects
to help stakeholders understand “what
it takes to do clinical work, write reports,
look at data integrity.”
“We are looking at medical education from
a holistic perspective using digital technology; it could be one way to add value in the
new world.”
GSK is also beefing up its internal medical capabilities – recruiting doctors “who
have what it takes” to share their expertise by
reaching out to the ecosystem.
Some of these plans are in sync with GSK’s
efforts internationally. Globally, GSK at the
end of 2013 unveiled three critical changes
to reform the way it interacts with HCPs including its intent to stop direct payments to
HCPs to speak on its behalf by 2016. It said
that instead it expected to develop new
digital, personal and real-time applications
for better delivery of information to HCPs. It
also noted that medical doctors within GSK
would have “more time” to talk with their external peers and answer questions about the
company’s drugs.
GSK is also aligning its public policy with
the Indian government’s initiatives in the area
of public health, adding value to the ecosystem, Vaidheesh said.
“There are multiple ways we are looking
at to create value by partnering and how we
deliver that value.”
Cross Functional Teams
GSK India has also put in place eight crossfunctional teams working towards facilitating seamless functioning within the
organization while also ensuring it stays nimble-footed in a highly competitive market.
Vaidheesh noted how one such cross
functional team – Operational Process Excellence – figures how to put in a process where
cost efficiencies are leveraged.
“They will use the Six Sigma technique; we
have hired some experts to work with this
team and to figure out what are the wastages in the existing processes and eliminate
such old processes.”
Similar cross-functional teams have also
been set up in the areas of business development and supply chain excellence, among
others. There is also a thrust on quality excellence, beyond that of just product quality
– essentially ensuring that people take accountability for raising the standards in every
job that they do.
Products And Pricing
The GSK India boss also underscored the
company’s intent to bring the right kind of
products to India, in the backdrop of the
country’s improving intellectual property
(IP) environment.
“In the respiratory area, we couldn’t launch
[certain products] because of IP reasons but
in today’s context, we are confident that the
Indian government is supportive of bringing
new IP assets. We will make some such assets
available in the next four to five years,” Vaidheesh added.
On pricing flexibility as was seen in the
case of Seretide Accuhaler last year, he noted
how the company was experimenting with
different models aimed at improving access.
Last year GSK India slashed prices of its
Seretide Accuhaler by 46% to INR540 (then
$8.3). Industry experts then told Scrip that
while Seretide Accuhaler has generally been
perceived as the device of choice by a large
number of physicians in key metropolitan
areas, affordability issues meant that its use
was generally limited to those with severe
asthma and chronic obstructive pulmonary
disorder (COPD).
Vaidheesh indicated that the price cut
had made “tremendous difference” and the
company was now able to reach a “large
proportion” of new patients coming into that
category.
“It [the price cut] seems to be working well.
We will continue with that approach. We’ve
tried that with Synflorix, our pneumococcal
conjugate vaccine. We are trying to evaluate whether by calibrating prices, we can increase access. It appears that we have made
huge headway in pneumococcal vaccines
and have been able to dramatically grow in
that area,” he said.
GSK expects to continue the price calibration exercise for key medicines, where it believes access is a challenge.
“We will continue to tweak and calibrate
prices borne out of the fundamental objective of access to medicines,” he added.
headline news
Sarepta Lashed Again; More Duchenne Market Doubt
T
he FDA has appeared to be in a love-hate relationship with
Sarepta Therapeutics Inc. On one hand, regulators agreed to
review Sarepta’s new drug application (NDA) for eteplirsen,
even though it was based on thin data, and have insisted the FDA has
been doing all it can to get therapies for patients with Duchenne muscular dystrophy (DMD) on the market as quickly as possible.
On the other hand, the FDA came down hard in its January review of
the eteplirsen NDA, giving an even harsher evaluation on April 21, with
regulators all but declaring the drug was as much as doomed.
The degree of uncertainty about
the dystrophin data hinders
discussion of its use as a surrogate
endpoint for eteplirsen
And it was a blood bath for Sarepta’s stock, which plummeted about
47%, before closing the day at $11.02, down $8.69, or 44%.
In its revised review, the FDA didn’t mince words, especially when it
came to addressing Sarepta’s accusation there were “key inaccuracies”
in the agency’s briefing documents issued in January ahead of what
ended up being a snowed-out meeting of the Peripheral and Central
Nervous System (PCNS) Advisory Committee, where it was to examine
the eteplirsen NDA.
“We do not agree with the applicant’s characterization of inaccuracies in the initial FDA briefing document,” regulators, including Robert
Temple, deputy director of the agency’s Office of Drug Evaluation I,
declared in the new documents, in which the agency takes Sarepta’s
“inaccuracies” arguments apart piece-by-piece.
Temple plans to speak at the rescheduled April 25 PCNS meeting, as
does Janet Woodcock, director of the FDA’s Center for Drug Evaluation
and Research.
Under Pressure
The FDA may be bringing out the heavy muscle in response to the
pressure, including from Capitol Hill, the agency has been under to
approve eteplirsen – and the fact a coalition of advocacy groups said
earlier this week they plan to pack the PCNS advisory committee
meeting with up to 1,200 people.
The FDA has set aside two and a half hours for the public hearing
portion of the planned 10.5 hour PCNS meeting, where Duchenne
advocates are hoping to have a second chance to be heard after US
regulators rejectedBioMarin Pharmaceutical Inc.’s DMD drug Kyndrisa
(drisapersen) in January, which was followed by more disappointment
when the agency refused to filePTC Therapeutics Inc.’s NDA for Translarna (ataluren).
DMD advocates – one of the most active and vocal among patient
advocacy communities – were successful in July 2014 in getting the
FDA to respond to a “We the People” White House petition, in which
Woodcock personally pledged that regulators were “willing to explore
the use of all potential pathways” for therapies against DMD, a progresscripintelligence.com
sive muscle degenerative disease, which primarily affects boys, often
killing them before they reach age 30.
In October 2014, the FDA found itself having to publicly explain – to
the extent the law allowed – about its communications and interactions with Sarepta over eteplirsen after the company had made several
public statements, which the agency apparently decided it needed to
clarify from its perspective, given the strife that was looming.
While the move to have Woodcock speak at the adcom is rare, her
involvement clearly signals the weight the agency is placing on the
eteplirsen review, “and her comments will hint at the FDA’s final decision,” said RW Baird analyst Brian Skorney. But, he said, “It is unclear at
this point whether this is a good thing or not.”
JMP Securities analyst Liisa Bayko warned to expect a “heartbreaking”
meeting for the DMD community and for the FDA to remain steadfast
on sticking to its principles, despite the public pressure.
With the FDA not providing any questions in advance of the PCNS
meeting – at least none that were posted on April 21 – and only “points
to consider” about the data for dystrophin expression and clinical measures and the design for any potential future studies, in the absence of
a vote, Bayko said to expect the debate on what conclusions the FDA
will make to continue to May 26, eteplirsen’s Prescription Drug User
Fee Act (PDUFA) action date, although she said she didn’t expect an
approval on the first round.
Troublesome Data
In the review the FDA released in January, regulators had raised considerable doubts about whether eteplirsen was effective in treating
DMD and called into question whether the investigational medicine
actually increased the levels of dystrophin, a protein essential for normal muscular structure and function and the lack of which is at the
heart of the condition.
“The degree of uncertainty about the dystrophin data hinders discussion of its use as a surrogate endpoint for eteplirsen,” the agency’s
drug reviewers said.
Two weeks before the FDA posted its initial review online of the
eteplirsen NDA, Sarepta had submitted four-year clinical efficacy data,
which included additional six-minute walk test and loss of ambulation data, which were compared to a historical control – a submission
the agency deemed a major amendment, which resulted in a threemonth delay, in which regulators moved the PDUFA from Feb. 26 to
May 26.
While Jefferies analyst Gena Wang said she thought the ambulation at the fourth year could be the strongest argument for Sarepta,
the FDA expressed its “concerns about the reliability, completeness,
and comparability of the clinical data for eteplirsen-treated patients
and external controls.” Additionally, the deterioration in measures that
precede walking ability including North Star Ambulatory Assessment
scores and rise time in eteplirsen were interpreted as similar, versus
natural history controls. Importantly, Wang said, most eteplirsen-treated patients had marked increases in rise time and several became unable or nearly so to rise from the floor, which she noted predicts a high
likelihood of loss of ambulation within one to two years, and illustrates
substantial disease progression.
headline news
AstraZeneca Teams Up With Venter, Sanger To Mine
Genomic Riches
Alex Shimmings [email protected]
A
Shutterstock: Ravital
straZeneca has entered into a series of early research collaborations in a bid to integrate genomics into the foundations
of its entire drug discovery and development infrastructure.
The three collaborations announced are with Craig Venter’s Human
Longevity Inc., as well as the UK’s Wellcome Trust Sanger Institute and
The Institute for Molecular Medicine in Finland. Further tie-ups are also
in the works and could be announced later this year, the company
said. Meanwhile, AstraZeneca also will create an in-house center for
genomics research, which is tasked with developing a bespoke database of genome sequences sourced from patients from its clinical trials plus other associated clinical and drug response data. No financial
details were disclosed, but the company expects to spend hundreds of
millions of dollars over the expected 10-year timeframe.
AstraZeneca claims the size and timing of the deals will give it a head
start over competitors in this fast-moving field, but it is following – to a
certain extent – in the footsteps of Amgen Inc., which in late 2012, paid
$415 million to enhance its drug discovery and development capabilities through the acquisition of deCODE Genetics – nearly three years
after the Icelandic genome sequencer emerged from bankruptcy.
AstraZeneca is poised to take advantage of recent leaps forward
in genomic technology that will allow the speedy sequencing of an
unprecedented two million genomes and home in on very rare differences between them. Pairing these findings with patients’ clinical data
should provide a “treasure trove” of information, which will be an invaluable genetic resource for drug discovery and development across
AstraZeneca’s core therapy areas of cardiovascular/metabolic, oncology, respiratory/inflammation and autoimmunity.
While the first genome to be sequenced took more than a decade
at a cost of about $1bn, the advances in next-generation sequencing
and the increased sophistication of data analysis means that this can
now be done in the space of a few days and for about $1,000, said
Mene Pangalos, executive vice president, innovative medicines and
early development (IMED). Talk of two million genomes is therefore
“not dreaming, but feasible,” he said.
Though the individual mutations found may be extremely rare,
brought together from such numbers they can illuminate biological
pathways of diseases and so provide new targets for drug development that will act on the pathway and be effective for much larger but
still defined groups of patients.
Embedding genomics across its R&D platforms will also allow AstraZeneca to select appropriate patients for clinical trials, and improve
personalization of therapies. The impact should be felt in every area
of R&D, Pangalos said, from early research at his IMED biotech unit to
later-stage development at AZ’s MedImmune biologics R&D arm, and
well into the post-launch phase where it will help in the understanding
of drug responses and toxicity profiles.
“But we cannot get to grips with this on our own, which is why we
have teamed up with the best academic and private partnerships
around the world,” he said.
The real challenge will be managing the huge amount of data produced and learning how best to interrogate it, Pangalos admitted. At
around five petabytes (1015) this is equivalent to a tower of compact
discs four times the height of The Shard in London, or alternatively, it
would take 10,000 years to listen to it all on your iPod, he said.
Under the collaboration with Human Longevity, AstraZeneca will
share up to 500,000 of its DNA samples from which full genomes will
be sequenced. San Diego-based Human Longevity will use its machine learning, pattern recognition and other analytical techniques.
These genomic samples will include those donated by patients under optional informed consent in AstraZeneca’s clinical trials over the
past 15 years, which will be supplemented by those donated over the
next 10 years. AstraZeneca will also gain access to Human Longevity’s
database of up to one million integrated genomic and health records
to add to its analysis.
Human Longevity was founded by genomic research pioneer Venter and others just three years ago (“stealing some really good employees from AstraZeneca before we started negotiations,” said Venter) and
along the way has raised $300m in two venture capital rounds. The
company aims to create the largest and most comprehensive database of whole genome, phenotype and clinical data in the world.
Venter said the AZ collaboration was a leap forward for the pharmaceutical industry in genomics, and should mean that genomics finally
starts delivering on its R&D promises. The lack of progress seen since
the first genome was sequenced amid great optimism in 2000 has
mainly been due to the small numbers of sequenced genomes and
the lack of phenotypic and clinical data to go with them, he noted.
Until now, only about 100,000 genomes have been sequenced.
So far it has been the more common genetic variants that have
been identified, but he stressed that it will be the discovery of the
many very rare variants coupled
with comprehensive phenotypCLICK
Read full story at:
ic data that will bring about the
long-awaited genomics-driven
http://bit.ly/1QwKAK6
paradigm shift in medicine.
P o l i c y & R e g u l at i o n B r i e f s
Contentious Indian Pricing
Orders Now In Court
A string of controversial price-related
orders by India’s National Pharmaceutical Pricing Authority (NPPA) are believed to have been challenged in court,
putting plans to enforce these rules in
limbo, at least in specific cases. Local
firm Wockhardt is said to have been
granted an interim stay by the Delhi
High Court in a case pertaining to the
freeze on prices of certain new nonscheduled formulations - drugs which
don’t figure on the country’s national
list of essential medicines (NLEM).
The applicability of wholesale price
index (WPI)-based price cuts for medicines already being sold below the ceiling prices has also been challenged by
the firm. Industry sources told Scrip
that the stay applies in both instances,
though details on Wockhardt’s petition or the interim relief granted could
not immediately be got. More legal action against the regulator is anticipated, a source suggested. Wockhardt did
not immediately respond to an e-mail
request for comment on its legal challenge. Scrip has previously reported
that the NPPA had made a seemingly
unusual clarification aimed at freezing
prices of certain new non-scheduled
formulations setting the stage for a
potential clash with industry over the
legality of the move. Formulations
that figure on Schedule 1 [essentially
comprising the NLEM 2015] of India’s
Drugs (Prices Control) Order (DPCO)
are typically subject to price caps in
India, while prices of non-scheduled
formulations [those not on Schedule
1] are generally subject only to price
monitoring. Prices of non-scheduled
medicines are permitted to be raised
up to a specified percentage during a
12-month period.
FDA Mycapssa Snub Whacks
Chiasma
The FDA tried to warn Chiasma Inc. in
2014 its single-arm, open-label Phase
III trial may not be enough to pass musscripintelligence.com
Canada Ups Pricing Pressure
Manufacturers of biosimilars and originator/reference products are set to
come under greater pressure to lower prices in Canada. In order to win reimbursement they will likely have to enter into pricing talks with the panCanadian Pharmaceutical Alliance (pCPA), which negotiates drug prices
on behalf of Canada’s public provincial and territorial drug plans. In a bid
to develop a more competitive and transparent market for biosimilars, the
pCPA has published its First Principles, aimed at guiding consistent negotiations for both biosimilars and their originator products. Payers, both public and private, will welcome the news. But manufacturers will approach developments with caution, say Sherry O’Quinn and Arvind Mani from PDCI
Market Access, a Canadian pricing and reimbursement consultancy.
ter for the agency to approve the company’s new drug application (NDA)
for its investigational acromegaly drug
Mycapssa (octreotide) and pointed out
having a controlled trial would be a
better option. But the company didn’t
listen and submitted its Mycapssa
NDA anyway – declaring regulators
hadn’t identified any issues that would
preclude the firm from doing so. Now,
Chiasma, however, is suffering the
consequences – getting smacked with a
complete response letter (CRL), which
had investors in a panic on April 18,
fleeing from the biotech’s shares. The
stock tumbled about 64% before landing at $3.75, a loss of $6.42, or about
63%. The FDA told Chiasma it needed to conduct another study because
regulators didn’t believe the NDA had
provided substantial evidence of efficacy to warrant approval in its current
form, CEO Mark Leuchtenberger told
investors and analysts during an April
18 conference call. This time, the FDA
wants a randomized, double-blind,
controlled trial with US patients and
of sufficiently long duration to ensure
that control of disease activity is stable
at the time point selected for the primary efficacy assessment, Leuchtenberger explained. But being unable to
more quickly commercialize Mycapssa
is leaving Chiasma in a vulnerable
financial position. Chiasma had reported last month that its unaudited
balance of cash, cash equivalents and
marketable securities was estimated to
be about $134m, which the company
expected to be sufficient to execute its
commercial plan, at least through mid2017, Leuchtenberger said. But, he
said, based on the FDA’s decision, “we
are now revisiting all priorities, with an
eye to extending the cash runway.”
BIO: Deals, Investment At Risk
If the US Supreme Court permits the
process for so-called inter partes reviews (IPRs) to remain on its current
course, not only will patent claims
held by innovator drug makers likely
continue to be invalidated at unprecedented levels, but investment in the
biopharmaceutical sector and partnering and acquisition deals among drug
companies are at greater risk of falling apart, said Tom DiLenge, general
counsel and head of public policy at
the Biotechnology Innovation Organization (BIO). Even if the IPR concerns
don’t kill a deal, the value of the assets
involved could be diminished – garnering less favorable terms and fewer
dollars in up-front cash, milestones or
royalties for the patent owner than it
otherwise may have snagged before the
filings for those types of petitions suddenly became all the rage, DiLenge told
Scrip. IPRs are trial proceedings held by
the US Patent & Trademark Office (US
PTO) Patent Trial and Appeal Board
(PTAB), which were created under the
American Invents Act of 2011 to be a
faster and more affordable alternative
to litigation for challenging patents.
headline news
Will 2016 Bring US Biosimilar Reimbursement Clarity?
A
s the emerging US biosimilars marketplace takes shape, payers are
expected to “actively” learn – both
clinically and economically – where the opportunities of those products may meet the
ongoing reality of the US healthcare system,
and they likely will adjust reimbursement
mechanisms over time accordingly, the authors of a new report sponsored by Amgen
Inc. said, declaring 2016 promises to bring
greater clarity to the American landscape
for the copycat biologics.
While they insisted biosimilars are
“uniquely poised” to increase value in the
US healthcare system, they said the ultimate impact of the products will be driven
by how payers respond to the launch of
the medicines, whether employer purchasers influence uptake, if there are factors
beyond the opportunity for savings, how
use evolves as stakeholders become more
familiar with biosimilars, how the naming
policy ultimately plays out and how stakeholders each evaluate and act on factors
related to reimbursement.
So far, the FDA has only approved two
biosimilars – Sandoz Inc.’s Zarxio (filgrastimsndz) on March 6, 2015 and Celltrion Inc.’s
and Pfizer Inc.’s Inflectra (infliximab-dyyb)
on April 5, 2016. But there are 351(k) applications pending before the agency for
Apotex Inc.’s pegfilgrastim and filgrastim,
Sandoz’s pegfilgrastim and etanercept and
Amgen’s adalimumab. Pfizer’s application
for its epoetin alfa biosimilar was rejected
last fall on its first try.
Zarxio, however, remains the only biosimilar on the US market, while Celltrion’s
and Pfizer’s product currently is held up in a
legal dispute, although the firms earlier this
month notified the plaintiff Johnson & Johnson subsidiary Janssen Biotech Inc., which
markets the infliximab innovator drug in the
US, Remicade, they intend to begin commercial sales of Inflectra no later than Oct. 2.
Celltrion and Pfizer already had agreed
not to put Inflectra on the US market until after the June 29 expiration of Janssen’s
patent ‘396.
So with only one biosimilar on the US
market, it’s unclear now how payers will
choose to manage coverage of the products – whether through patients’ pharmacy
or medical benefits – which likely will influence the use of the drugs, the authors said
in the 2016 Trends In Biosimilars Report.
A prescription drug covered through the
medical benefit is typically administered by
a healthcare professional in the inpatient
or outpatient hospital, doctor office, home
infusion or ambulatory center settings,
while a medicine covered under the pharmacy benefit is generally self-administered
by the patient.
Payers likely will face the same use management and tracking issues in the medical
benefit specialty category for biosimilars as
they do already for innovator biologics, the
report authors pointed out.
They also anticipated more direct contracting by employer purchasers with integrated delivery networks (IDNs) for biosimilars.
“We expect to see biosimilars within
formularies, but the placement within the
formulary, whether to an existing tier or
creating a new tier, is undetermined,” the
Amgen authors said.
Shortages Impact
The authors of the report emphasized that
as more manufacturers plan to enter the biosimilar market, it will become “increasingly
important” for stakeholders to have an understanding of each company’s manufacturing capabilities, quality assurance process, reputation for consistent supply and
plans for avoiding drug shortages, which
they noted can have a “dramatic fiscal impact” on hospitals and lead to a substantial
number of changes in treatment, which
may result in a patient being switched a
drug with a “weaker evidence base.”
Concerns about reliability of supply, they
said, are “well-founded” based on the generic manufacturing industry’s history with
the production of sterile injectables – a segment of the pharmaceutical market that
has “suffered numerous shortages” over the
years, largely due to quality control issues.
They pointed to a recent economic
analysis which suggested that shortages
of injectable drugs may be associated
with inadequate reimbursement for multisource medicines predominantly covered
by Medicare – “a risk factor that also might
apply in the future for certain classes of
biosimilar products.”
A payer’s pharmacy and therapeutics advisory committee may evaluate a manufacturer’s reliability, safety and quality control
history, in addition to its safeguards to ensure manufacturing capacity and dependability, when choosing one product over
another, the Amgen report authors said.
“Payers, IDNs and providers may make
their degree of confidence in a manufacturer’s ability to avoid shortages a key
consideration when evaluating their preferences among multiple biosimilars as well
as the reference product,” they said.
“There are a lot of challenges to consider before jumping to adopt a biosimilar,” said Amgen’s “Editorial Council,” which
consists of medical and pharmacy directors representing a mix of managed care
organization and employer and benefit
design consultants, who collaborated on
the report. “We have been so heavily impacted by drug shortages at our organizations that if we have a good stable supply of a very necessary product to treat
our really sick patients, we’re going to
stick with that until we can truly ascertain
whether or not the biosimilar is going
to be supplied in the quantities that we
need it.”
Safety, Education, Friction
The availability of biosimilars in the US, the
report authors argued, brings with it the
need to monitor patient safety related to
use of these new products.
“With biosimilars, it is imperative that
regulatory and industry come together to
create the most appropriate pharmacovigilance and safety monitoring process,
inclusive of agreed-to naming guidance, to
understand patient experience and to be
able to proactively, quickly and accurately
identify potential safety signals across categories/medications,” they contended. “All
constituents participating in the healthcare system are vested in the safe and appropriate use of biosimilars.”
They also argued there’s a need for more
physician, pharmacist and patient education around the appropriate use and considerations associated with biosimilars.
headline news
New Uk Industry Body To Promote Flagging
Biosimilar Market
Ian Schofield [email protected]
T
For example, with biosimilar infliximab (a version of Merck &
Co/J&J’s Remicade), “we saw very fast uptake in pockets in the
south, and in the north it was quite a bit slower. There is very much
a regional approach, while in the Nordic countries there is a much
more centralized approach.”
Moreover, older drugs such as G-CSF have done quite well in the
UK and have taken the majority of the market, de Gavre observed.
And while biosimilar infliximab has taken a 30% market share
across the UK since its launch in early 2015, this is “ slower than we
would like to see.”
Shutterstock: Digital Deliverance
he British Generic Manufacturers Association has become the
latest pharmaceutical trade body to set up a dedicated sector
group to promote the use of biosimilar medicines, following
a similar move by Medicines for Europe, which represents national
generic associations across Europe.
Against a backdrop of patchy and often slow uptake of biosimilars in the UK, the British Biosimilars Association, which was formally
launched on April 18, says its objective is to raise awareness of the
benefits of these products among doctors, patients and the NHS.
In doing so, it will also aim to counter information distributed by
what its chair, Tim de Gavre, described as those with “vested interests in the failure of biosimilars.”
The new body was welcomed by Keith Ridge, chief pharmaceutical officer of NHS England, who said that biosimilars had “enormous
potential to deliver increased patient access as well as savings to the
NHS which can be reinvested elsewhere,” and that he looked forward
to working with the BBA to make clinicians aware of this potential
and to encourage biosimilar competition “wherever appropriate.”
At present, the UK biosimilars market consists of seven substances: somatropin, follitropin alfa, filgrastim, infliximab, epoetin alfa,
insulin glargine, and etanercept. The number is set to rise, the BBA
says, in line with patent expiries on originator drugs, greater clinical awareness and knowledge, and guidance from bodies like the
National Institute for Health and Care Excellence (NICE).
But while biosimilars are forging strongly ahead in some markets,
notably the Nordic countries, the UK is lagging behind in uptake, in
many cases because of issues such as lack of prescribing incentives,
low awareness among doctors, and lack of understanding of their
relationship to the originator drugs. Moreover, uptake varies widely
from one region to another.
According to de Gavre, the problem lies in the organization of
the NHS and the lack of consistency among attitudes to biosimilars
across the regions of the UK. “There is not one NHS, but about a
thousand different NHSs, depending on the region, depending on
personalities, and as a result you have different approaches to biosimilars across the country,” he told Scrip in an interview.
Explaining The Benefits
Warwick Smith, director general of the BBA and the BGMA, said “six
of the top 10 medicine expenditures by the NHS are on biological
drugs.” Biosimilars, he said, offered “a real opportunity to increase
patient choice and access to this vital class of medicines as well as
delivering value to the NHS.”
But the UK has to maximize the potential offered by the increased
use of biosimilar medicines, Smith said, as the cost savings that could
be achieved would “release much needed funds to the NHS when
budgets are under significant pressure.”The BBA’s mission, he declared,
was to “explain the benefits of biosimilar medicines and thus to promote their use.”
What does this mean in practice? According to de Gavre, it means
being the “thought leaders and promoters of this new class, by working collaboratively with the NHS, continuing to raise awareness, and
pursing as many educational initiatives as we can.”The BBA has to be at
forefront of educating key stakeholders within the NHS, whether pharmacists, consultants, nurses, Clinical Commissioning Groups (CCGs) or
NHS England, he said.
One challenge facing the uptake of biosimilars is the lack of incentives, particularly in the case of physicians who do not always benefit
from the savings achieved from biosimilar use. “You must allow doctors
to see that at least some of the savings are invested into their departments so that they can improve the quality of patient care,” de Gavre
observed.
A good example of how this could be done, he said, was the
2015 gain-share agreement signed by University Hospital Southampton NHS Foundation Trust and local CCGs on a program to
switch patients from Remicade to biosimilar infliximab (Hospira’s
Inflectra and Celltrion’s Remsima, which is marketed by Napp
Pharmaceuticals).
According to a report on the outcome of this program by Fraser
Cummings and Violeta Razanskaite, published in January this year, 134
patients were switched to the biosimilar version, with initial cost savings of about £300,000 ($430,000) “without adverse effects to patient
care.” They concluded that a gain-share agreement was an effective
way of ensuring that cost savings were distributed equally among the
service providers and commissioners, and invested in local nursing,
pharmacy and clerical services.
headline news
AACR: Three Promising Anticancers From
Loxo Oncology, Ignyta And Beigene
John Davis [email protected]
I
nvestigational anticancer drugs aimed at
new potential targets, particularly those
involving genetic abnormalities that can
be identified for diagnostic purposes, were
the focus of presentations on their safety
and efficacy in Phase I studies at this year’s
American Association for Cancer Research
(AACR) meeting.
ied included the thyroid, salivary glands,
lungs and gastro-intestinal tract.
The majority of reported adverse events
were mild to moderate in nature, including
fatigue, constipation, anemia, pleural effusion and syncope, the researchers reported.
Neurotrophic TRK (NTRK) genes that
code for TRKs can fuse to other genes and
Progress in this area should eventually allow
cancer therapies to be chosen on the basis of
tumor genetics, rather than on the site of the
tumor in the body. New targets reaching the clinic
and highlighted at AACR included a tropomyosin
receptor kinase (TRK) inhibitor
Progress in this area should eventually
allow cancer therapies to be chosen on
the basis of tumor genetics, rather than on
the site of the tumor in the body. New targets reaching the clinic and highlighted at
AACR included a tropomyosin receptor kinase (TRK) inhibitor, a new oral tyrosine kinase inhibitor, and a RAF protein inhibitor.
Analysts at Credit Suisse noted that other
potential new targets, like OX40 and STING,
are also believed to be some of the more
attractive of the numerous targets under
early-stage evaluation at the moment.
Stamford, Connecticut-based Loxo Oncology Inc. is focused on developing selective medicines for genetically-defined
cancers, and is now conducting Phase II
studies with its TRK inhibitor LOXO-101,
that has shown initial signs of efficacy in
Phase I.
David Hong, associate professor at the
MD Anderson Cancer Center in Houston,
Texas, reported at the AACR meeting that
all six patients with solid tumors and TRK
fusion genes treated in a Phase I study had
significant regression of their cancers following administration of LOXO-101. The
cancers were at various sites in the body,
and five of the six achieved partial confirmed responses. The site of tumors stud18 | Scrip intelligence | 29 April 2016
cause growth signals that lead to cancer
at many sites in the body, the company
noted, and LOXO-101 is being evaluated in a global Phase II study in patients
with solid tumors containing TRK gene
fusions, and in a Phase I trial in pediatric
patients. Loxo Oncology raised $76.2m in
gross proceeds in a follow-on offering on
Nasdq in Nov. 2015, having had an IPO in
Sept. 2014, and expects to start a Phase I
study with a next generation TRK inhibitor
LOXO-195 in 2017.
Entrectinib Against
Rearranged-Gene Tumors
Another US company developing targeted
anticancers is San Diego’s Ignyta Inc. that reported promising Phase I data at the AACR
meeting with its oral tyrosine kinase inhibitor entrectinib. Entrectinib targets solid
tumors containing activating alterations
in various genes including NTRK1, NTRK2,
NTRK3, ROS1 or ALK.
With regard to efficacy, tumor regression
was seen in 20 out of 25 evaluable patients
(80%) including patients with NTRK, ROS1
and ALK gene rearrangements, and in six
different tumor types. On safety, where
Ignyta has a larger dataset of 119 patients,
entrectinib’s safety was deemed to be ac-
ceptable, with the majority of treatmentrelated adverse effects being fatigue (44%),
dysgeusia (41%), paresthesia (28%), nausea
(24%) and myalgia (22%). Ignyta raised
gross proceeds of $48m from a Nasdaq
IPO slightly earlier than Loxo Oncology, in
March 2014, and a potentially registrationenabling Phase II study, STARTTRK-2, is currently enrolling patients.
RAF Protein Inhibitor
Promising
A Phase I study of BeiGene Ltd.’s BGB-283
that is targeted against the RAF family of
proteins was associated with one complete
response, two confirmed partial responses,
and 15 cases of stable disease among a
group of 29 patients, reported Australian researcher Jayesh Desai.
The responders had different tumors at
different sites in the body: the complete
responder was diagnosed with melanoma
with a BRAF V600E mutation, and treatment is ongoing after 342 days. The partial
responders included one patient with endometrial cancer and a KRAS mutation and
another with a thyroid cancer with a BRAF
V600E mutation. The two partial responders had been on treatment for 455 days
and 574 days respectively.
BGB-283 is believed to work differently
from marketed BRAF V600E inhibitors, inhibiting the activity of all RAF proteins,
Desai commented. In the Phase I study,
conducted in Australia and New Zealand,
BGB-283 had a half-life of around 110 hours,
and dose-limiting toxicities included grade
4 thrombocytopenia seen in three patients
and grade 3 liver enzyme elevation in one
patients, with the most frequent adverse
events being fatigue (52%), thrombocytopenia (39%), decreased appetite (39%),
hand-foot syndrome (35%), dermatitis acneiform (32%) and hypertension (32%).
BeiGene raised $158m in a US IPO in Feb.
2016 and is currently conducting all clinical
development on BGB-283, although Merck
KGaA has an exclusive license to develop
and commercialize the product outside of
China in a deal signed in 2013.
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R&D Bites
AbbVie Continues To
Chase Gilead
AbbVie Inc.’s once-daily, ribavirin (RBV)free, pan-genotypic regimen, ABT-493/
ABT-530, achieved impressive results in
a Phase II study of genotype 2/3 hepatitis C patients, but it still might not
be enough to dethrone current market
leader Gilead Sciences. AbbVie presented data from a number of clinical trials
for its ABT-493/ABT-530 regimen at the
European Association of the Study of the
Liver (EASL), held from April 13 to 17 in
Barcelona. New data from the SURVEYOR-2 study, a four-part trial designed to
evaluate the safety and efficacy of ABT493 and ABT-530, with or without RBV,
in adult patients with genotypes 2, 3, 4,
5 or 6 chronic HCV infection who were
new to therapy or had failed previous
treatment with pegylated interferon,
showed that with 8 weeks of treatment
97-98% of genotype 2/3 patients without
cirrhosis achieved sustained virologic response at 12 weeks post-treatment
Kymab, Heptares Enter GPCR
Targeting Pact
Two of Britain’s leading science innovators – Mab specialist Kymab Ltd. and
GPCR-targeting Heptares Therapeutics
– are joining forces to discover, develop
and commercialize new antibody drugs
targeting a number of G protein-coupled
receptors, focusing initially on immunooncology. GPCRs are widely expressed
on cells of the innate and adaptive immune system and play key roles in modulating cell migration and recruitment
to the tumour environment, activation,
survival, proliferation and differentiation. GPCRs act at critical checkpoints
that can be targeted by novel immunotherapy antibodies. Around 40% of all
currently marketed drugs act on one or
more of the 826 known GCPRs in the
body, which are a large family of cell surface receptors linked to G proteins and
cellular signalling pathways which are
activated by natural or other molecules
and have been found to be critically involved in a broad variety of diseases.
BI, Lilly To Study Jardiance For
Heart Failure
Boehringer Ingelheim and Eli Lilly will launch two outcomes trials within
the next 12 months investigating their jointly developed diabetes medicine Jardiance (empagliflozin) as a treatment for people with chronic heart
failure – enrolling patients both with and without type 2 diabetes. Jardiance was the first diabetes treatment to demonstrate a reduction in the risk
of cardiovascular (CV) death in the dedicated CV outcomes trial, EMPAREG OUTCOMES. In September 2015, Lilly and Boehringer received high
praise when they release full data from the CV outcomes study, and while
not all areas of the trial were successful, the data were impressive. Jardiance, a selective inhibitor of sodium glucose cotransporter 2 (SGLT2), saw
a 38% reduction in CV deaths in the EMPA-REG study. A notable result
as 50% of deaths among people with type 2 diabetes are caused by CV disease. This data propelled Jardiance ahead of its competitors, as while other
SGLT-2s are being studied in CV outcomes trials the results will not be
available for several years.
Merck’s Barr On Treating
Neglected HCV Patients
New drugs for the hepatitis C virus
(HCV) often aim to treat “garden variety” patients, who despite their HCV are
otherwise healthy, but Merck & Co. Inc.
also is focused on underserved populations that frequently are left of out of
clinical trials. “We decided that in our
clinical program we weren’t going to
focus on that great middle population
that has been the subject of clinical trials – the garden variety HCV patient.
If you want to really impact HCV, you
need to focus on the entire population,
including patients that haven’t been
paid attention to,” Eliav Barr, vice president of infectious diseases at Merck Research Laboratories, told Scrip.
NIH Shut Down In
Contamination Probe
The National Institutes of Health (NIH)
on April 19 acknowledged that an ongoing investigation into contamination at
its sterile production facilities has resulted in the shutdown of two of those operations – declaring they were not in com-
pliance with quality and safety standards.
The facilities involved are a laboratory
at the National Cancer Institute (NCI),
which was engaged in cell therapy production, and a facility at the National
Institute of Mental Health, which was
producing positron emission tomography materials.
Tackling Tough-To-Treat
Patients
It’s no longer a matter of which company will achieve the highest hepatitis
C cure rates first, but which one will
most effectively treat patients who fall
through the cracks, since Gilead Sciences Inc., Merck & Co. Inc. and AbbVie
Inc.’s latest antiviral drug cocktails cure
nearly all patients. Data presented during the European Association of the
Study of the Liver’s (EASL’s) International Liver Congress from April 13 to
17 in Barcelona showed that approved
and investigational direct acting antiviral (DAA) therapies from the three
companies are highly effective for most
or all patients with the hepatitis C virus
(HCV), including individuals who relapsed after prior DAA treatment and
people with hard-to-treat HCV genotypes or concurrent medical conditions.
Expert View
Patient Registries Prove Value As Drug
Development Tools
Mandy Jackson [email protected]
I
t’s easy for pharmaceutical and biotechnology companies to get
caught up in biomarkers and scientific clinical endpoints as the end
goals in drug development, but a novel, practical approach is gaining momentum: asking the patient what they need or want from
new medicines.
More companies are using patient registries or creating their
own registries to do more than track side effects after new drugs
hit the market. The data are being collected and analyzed to inform
development programs, assist in clinical trial design and, increasingly, to show regulators and payers the value of their medicines in
the eyes of patients. Such efforts are beginning to pay off, generating data that can’t be gleaned from talking to key opinion leaders
or reading lab test results.
South San Francisco-based True North Therapeutics recently
launched the COMPASS Registry for patients with cold agglutinin disease (CAD) and other autoimmune hemolytic anemias
with several goals in mind: to gain a better understanding of the
natural history of CAD, identify meaningful biomarkers, and to
engage patients and doctors in a way that may accelerate drug
development.
True North is developing therapies for complement-mediated
diseases and the company is in the middle of a Phase Ib clinical
trial testing lead drug candidate TNT009 in the treatment of CAD.
The company raised $40m in series C venture capital in December
to fund a Phase II trial, which is expected to start in 2017 and could
support accelerated approval of TNT009.
Vice President of Corporate Development Adam Rosenthal told
Scrip that True North began to think about establishing a CAD
patient registry around mid-2015 as a way to learn more about
the natural history of the disease and identify patients with CAD
and other types of anemia that may be complement-mediated.
“We wanted to be the ones to lead the effort,” Rosenthal said.
“We wanted to know who they are, where they are, and understand
them with the goal of treatment in mind. In the course of developing our therapy, we want to make sure we are doing it with the
right patients in mind.”
True North connected with Patient Crossroads, which has a
technology platform that enables patient registries, and consulted
with CAD patient Betty Usdan, who runs the web site ColdAgglutininDisease.Org and the CADdy Chatter Facebook page for CAD
patients.
At first, Usdan helped True North contact CAD patients about
providing blood samples, so that the company could gather
some data from people with the rare anemia. About 40 people
from Usdan’s community of about 400 CAD patients provided
blood samples. Now, she’s letting CAD patients know about True
North’s registry.
“We were surprised at how quickly patients gave blood samples,” Rosenthal said. “I think they do it because it allows them to be
more active in their healthcare. They’re providing a lot of benefits
to the research field about this disease.” On the COMPASS Registry’s
web site, patients can fill out a survey about their experience with
the disease, find out how to provide blood samples and link their
electronic medical records (EMRs) to the web site. All of the personal medical information is de-identified by Patient Crossroads
before True North or any other researcher accesses the registry’s
database. If True North or another company wants to contact patients about participating in a clinical trial, Patient Crossroads is the
go-between.
Data Collection And Doctor Education
Usdan told Scrip that she’s hopeful True North’s registry, which will
be open to scientists and drug developers outside of the company,
will help doctors understand how to treat CAD patients. She notes
that it can also be a resource for newly diagnosed patients, along
with her web site and Facebook page, to find out how other are
patients are handling the disease and being treated by physicians.
“You should see the comments I get from [doctors] who’ve never seen a case. They still prescribe old treatments; some just say
‘Keep warm and keep covered.’ This [registry] is a way of informing
the medical community and maybe helping the patients as well,”
Usdan said.
CAD has no approved treatments other than steroids, like dexamethasone, and off-label use of Rituxan (rituximab) for relapses
when hemoglobin is especially low. Usdan, a New York native, also
treats her anemia by living in Florida to keep bearably warm during
the fall and winter months.
Given the lack of CAD therapies, there seems to be a clear need
for more research around the disease and new treatment options.
To that end, True North is contacting hematologists who treat a lot
of CAD patients and is asking the doctors to encourage their patients to join the COMPASS Registry.
“We’re trying to get as many people as we can,” Rosenthal said.
“There will be real-time analysis. At the end of the year we will
do more analysis to see if there are additional questions that we
should ask or additional blood tests we should run. We have a
goal of eventually publishing our research. It will all depend on
the robustness of the data and how much we are able to collect
per patient.”
PatientCrossroads CEO Kyle Brown told Scrip that the interest from biopharma companies in setting up patient registries
as a means for informing R&D programs and future commercial
strategy is growing, due in large part to US FDA requirements
to include patient voices in the drug development process. The
agency is required under the Food and Drug Administration
Safety and Innovation Act
(FDASIA) to create new opCLICK
Read full story at:
portunities for patients’ voices to be heard in the regulahttp://bit.ly/1T8Kzhi
tory process.
S t o c k wat c h
No Earnings Disappointments Are The New Black
andy smith
A
s the first-quarter 2016 earnings season got underway for life
science companies last week expectations were not high. In
the event the first week of announcements was not as bad
as many had feared. The stock market typically over-reacts to both
good and bad news so in the absence of a wholesale missing of analysts’ consensus estimates, by Thursday April 21, the market had gotten a little ahead of itself.
However, last week could not have gotten off to a worse start with
next-generation sequencing company Illumina Inc. reporting its
third quarterly sales miss in the last year as a result of weak mid-range
instrument and European sales. We own Illumina in order to benefit from the future integration of liquid biopsies and personalized
medicine in therapeutic oncology. While the sales of sequencing
consumables did not contribute to Illumina’s 4% sales miss, I could
not help agreeing with the analysts from JP Morgan who described
its results as “disappointing” since it raised the spectre of saturation of
sequencing capacity. The analysts from Cowen described its issues
as “self-inflicted and fixable” but as a significant component of the
NASDAQ Biotech Index (NBI), Illumina’s 19% share price drop over the
week cast an early shadow over the sector.
But it was Roche Holding AG (a previously spurned would-be acquirer of Illumina Inc.) and Johnson & Johnson (J&J) to the rescue on
April 19 – the day after Illumina’s quarterly announcement. Roche beat
analysts’ sales expectations by 1%. The analysts from Jefferies and JP
Morgan both described Roche’s results as “solid” while those from Citigroup attributed the sales beat to Roche’s pharmaceutical division and
more specifically the CHF0.4bn contribution from Tamiflu (oseltamivir)
in a late influenza season. Hardly the most bullish and reproducible assessment of Roche’s first quarter but after Illumina the absence of a big
disappointment seemed to be the new black. In the same way J&J’s results were also described as “solid” by the analysts at JP Morgan and “inline” by those at Jefferies. Like Roche, J&J’s results were driven entirely
by its pharmaceutical division and, in particular, its anti-inflammatory
product Remicade (infliximab). The absence of any effect from a biosimilar Remicade in the next year was incorporated into J&J’s guidance
and this bravado may have been partly responsible for its share price
strength. With the recent FDA approval of such a product, Inflectra (infliximab-dyyb) (Also see “Celltrion/Pfizer Inflectra Second US Biosimilar;
Many Firsts” - Scrip, 6 Apr, 2016.), this may appear a little cavalier at some
point in the near future. J&J and Roche were both able to raise their fullyear earnings guidance on the basis that foreign exchange translations
are not now as bad as they appeared to be at the start of the year and
the share prices of both ended the week up about 2.5%.
Re-affirming the “no disappointment” trend of Roche and J&J
were the quarterly results of Abbott Laboratories Inc. and Novartis
AG. These were described by the analysts from JP Morgan as “better
than expected” and “ahead of company consensus,” respectively. Even
with a 1% sales miss that necessitated operational cost cuts in order
to beat analysts’ earnings estimates, the Novartis share price finished
the week up about 2.5%. Outside the focus on the quarterly numbers,
both Abbott and Novartis used their commentaries to add to two
current controversies. Abbott is a company that has evolved through
acquisitions like the pharmaceutical businesses of BASF SE, and with
its more recent eschewing of developed market generic pharmaceuticals it has embraced established products in emerging markets.
However, its CEO noted that the increase in valuations of late had
“sidelined” its non-organic expansion in this area. The CEO of Novartis
lamented the death of the “hockey stick” sales profile associated with
successful blockbuster drug launches. With the company’s last such
drug launch being less than three years ago, such comments feel like
“hard cheese” from a firm that has commercial operational issues, and
is in the wrong (cardiovascular) therapeutics space at the wrong time
(when payers have already drawn first blood with the PCSK9s).
The biggest relief of the week came from was at Biogen Inc. Its
first-quarter results were nowhere near as bad as were expected and
its share price finished the week up 4.7%. Earnings were driven by
operational cost cuts, after the company’s all-important multiple
sclerosis product (MS) Tecfidera (dimethyl fumarate) missed consensus sales estimates despite a significant DTC advertising campaign.
The analysts from Cowen described Biogen’s entire MS franchise as
“treading water” and at the very least, Biogen was probably fortunate
to have announced “uneventful” earnings (in the words of JP Morgan’s analysts) on a day the whole sector was in favour. The analysts
from Leerink Partners were more critical and having a ‘Market Perform’
rating on Biogen reduced their share price target and described its
pipeline as “risky and remote.” While Biogen’s share price finished up
over 5% on that particular day, I also found myself agreeing with the
analysts from Piper Jaffray who have a ‘Neutral’ rating on Biogen and
who suggested that it “has to do something substantive to improve
its long-term outlook when faced with multiple competitive threats.”
This “something substantive” may not be the rumored divestment of
its recently established and growing hemophilia franchise, although
like the frequent shedding of “family silver” products by AstraZeneca
PLC, it would likely support Biogen’s earnings, but not its sales, for a
few quarters after divestment.
Biogen was reticent to discuss the rumored divestment of its hemophilia franchise possibly because it represents the failure of joinedup thinking between its R&D and commercial groups. Imagine how
embarrassing it would be to have developed two new long-acting
biologic products for hemophilia when another company (also with
no history in the therapeutic area) comes along with a product that
is likely to put all long-acting recombinant Factor VIIIs for hemophilia
A in the shade. Roche’s Phase III breakthrough designation product
ACE910 is just such an embarrassing product and interestingly one
that might benefit from having Biogen’s hemophilia products together in its stable.
The Magna Biopharma Income fund holdings include Illumina,
BMS, Roche and Abbott.
Andy Smith is chief investment officer of Mann Bioinvest. Mann Bioinvest is
the investment adviser for the Magna BioPharma Income fund which has
no position in the stocks mentioned, unless stated above. Dr Smith gives
an investment fund manager’s view on public life science companies. He
has been lead fund manager for four life science– specific funds, including
International Biotechnology Trust and the AXA Framlington Biotech Fund,
and was awarded the Technology Fund Manager of the year for 2007.
P i p e l i n e Wat c h
Scrip’s weekly Pipeline Watch tabulates the most recently reported
late-stage clinical trial and regulatory developments from the more
than 10,000 drug candidates currently under active research worldwide.
CLICK
Visit scrip intelligence.com
for the entire pipeline with
added commentary.
Late-stage clinical developments for the week 15-21 April 2016
Lead Company
Partner Company
Drug
Indication
Market
SUPPLEMENTAL REGULATORY APPROVAL
Boehringer Ingelheim GmbH
–
Gilotrif (afatinib)
squamous non-small cell lung cancer
(NSCLC)
US
Merck & Co.
–
Keytruda (pembrolizumab)
metastatic non-small cell lung cancer
(NSCLC)
Canada
–
plecanatide
chronic idiopathic constipation
US
Marinus Pharmaceuticals Inc.
–
ganaxolone intravenous
seizure disorders
US
GW Pharmaceuticals plc
–
Epidiolex (cannabidiol)
tuberous sclerosis complex
US
FCX-013
scleroderma
US
REGULATORY FILING ACCEPTED
Synergy Pharmaceeuticals Inc.
ORPHAN DRUG DESIGNATION
Fibrocell Science Inc.
Intrexon Corp.
Delmar Pharmaceuticals Inc.
–
VAL-083 (dianhydrogalactitol)
ovarian cancer
US
BioMarin Pharmaceutical Inc.
–
BMN 250
Sanfilippo syndrome
EU
Spectrum Pharmaceuticals Inc.
–
Evomela (melphalan)
multiple myeloma
US
–
Keytruda (pembrolizumab)
Hodgkin’s lymphoma
US
–
Mycapssa (octreotide) capsules acromegaly
US
–
AC-170 (cetirizine)
allergic conjunctivitis
US
–
CR845
post-surgical pain
US
Dr Reddy’s Laboratories
–
Zembrace SymTouch
(sumatriptan)
migraine
US
Tris Pharma Inc.
–
Dyanavel XR (amphetamine)
attention-deficit hyperactivity disorder
(ADHD)
US
Amgen Astellas
BioPharma KK
Astellas Pharma Inc.
Repatha (evolocumab)
familial hyperchoesterolemia and refractory
hypercholesterolemia
Japan
Chugai Pharmaceutical Co. Ltd
(Roche)
Taisho Toyama
Pharmaceutical Co.
Ltd.
Bonviva (ibandronate sodium
hydrate) tablets
osteoporosis
Japan
BREAKTHROUGH THERAPY DESIGNATION
Merck & Co.
COMPLETE RESPONSE LETTER
Chiasma Inc.
REGULATORY FILING
Nicox SA
PARTIAL HOLD LIFTED
Cara Therapeutics Inc
PRODUCT LAUNCH
Source: Sagient Research’s BioMedTracker
Appointments
Zymeworks Inc., a biotherapeutics company which specialises in antibody development, has appointed Diana Hausman
chief medical officer (CMO). Hausman is a
board certified medical oncologist who has
previously served as CMO at Oncothyreon.
She has also held positions at Zymogenetics, Berlex and Immunex, and brings more
than 15 years’ of clinical drug development
experience to Zymeworks.
Michael Pragnell who steps down after
the completing of his second three year
term as chair on October 31, 2016. Prior
to his position at University of Cambridge,
Leszek was previously chief executive of
the medical research council and deputy
rector of Imperial College London. He is a
founding Fellow of the Academy of Medical Sciences and was awarded a Knighthood in 2001.
Millenium Health has appointed Ronald
A. Rittenmeyer chair and CEO, replacing
Brock Hardaway, who has led the health
solutions company since 2013. Rittenmeyer previously served as chair, president and CEO of Expert Global Solutions,
before which he held leadership roles at a
range of companies including Safety-Kleen
Inc., AmeriServe and PepsiCo. Rittenmeyer
is currently on the board of directors of
American International Group Inc. (AIG),
Tenet Healthcare Corporation, IMS Health
Inc. and Avaya Inc.
The Precision Medicine Catapult has
appointed Belinda Quinn CEO. Quinn
trained as a doctor and has been chief
clinical officer of the precision medicine
catapult for the past six months. She
previously held executive and transformational change roles across the public
and private sector including big pharma,
global management consulting, the NHS
data and regulator in the UK, Australia and
the Middle East.
Cancer Research UK has appointed
Professor Sir Leszek Borysiewicz vice
chancellor of the University of Cambridge as chair – effective November
1, 2016. Borysiewicz will take over from
Scrip
Biocom has appointed Dina Lozofsky
executive director of its new office in Los
Angeles. Lozofsky most recently served as
assosicate director for licensing and business development at University of California, Santa Barbara’s Office of technology
and industry alliances. She also has worked
in the technology transfer offices of both
University of California, Los Angeles and
University of Southern California.
Oncology focused Galena Biopharma
has appointed Mary Ann Gray to its board
of directors. Gray is an experienced corporate director for both public and private
companies and is president of Gray Strategic Advisors, LLC. Previously she was at the
Federated Kaufmann Fund focusing on the
both public and private healthcare investments. Prior to this, Gray was a sell-side biotech analyst. Earlier in her career, Gray held
scientific positions at Schering Plough and
NeoRx, managed pre-clinical toxicology
studies for the National Cancer Institute
through Battelle Memorial Institute, and
worked in a hospital laboratory.
Immunomedics Inc. has appointed Sol
J. Barer special advisor to the chair. Barer
is currently managing partner of SJ Consulting and previously, he served in various senior management roles at Celgene
Crop. including executive chair, chair, CEO,
president and COO. He also serves on the
board for Teva Pharmaceuticals, Contrafect, Amicus Therapeutics, and Aegerion
Pharmaceuticals.
eleanor Malone @ScripEleanor
ian Schofield @ScripIanS
John davis @john023davis
[email protected]
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alex shimmings @ScripAlexS
ashley yeo @ashleypyeo
sarah weir @ScripSarah
[email protected]
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sukaina.virji @scripsuki
lisa lamotta @BioWriterChik
[email protected]
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courtesy of www.shutterstock.com
unless otherwise stated.
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[email protected]
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