3794 - Scrip

Transcription

3794 - Scrip

March 18th 2016 No 3794
scripintelligence.com
New Active Substance Launches Plummet
Rodrigo Kristensen/shutterstock.com
The number of new active substances
launched in 2015 fell by nearly a third
compared with the previous year. But there is
no need for despair – beating 2014’s recordbreaking year of 63 new active substance
(NAS) launches was always going to be a tall
order, and 2015’s tally actually came in at a
very respectable 46.
This makes 2015 the second-best year
for launches of new active substances (i.e.,
new chemical and biological entities, and
excluding generics, new formulations and
new combinations of old products) for some
time, and it is a close third in terms of overall
numbers. In fact, the past three years were the
best on record, and looking at the graph an
upward trend can be discerned stretching back
to 2007. That’s almost a decade of growth.
As such, it appears that the drop in NAS
launches last year was more to do with 2014
being anomalously high than anything that
went wrong in 2015, and it was apparent
early on that these heights would not be
reached again anytime soon. As we explored
last year, there was a glut of products
HIGH STANDARDS: Drop in 2015’s NAS launches
more to do with 2014 being anomalously high
reaching the market for just one indication:
hepatitis C. No fewer than seven NASs were
launched for this disease in 2014 as the
explosion of R&D for direct-acting antivirals
came to fruition.No NASs were launched
for HCV in 2015. Similarly, four products in
the SGLT2 inhibitor class were launched for
diabetes in 2014, but none this year.
The full alphabetical list of NASs for 2015
is found in Table 1. Included in the table are
the drugs’ generic and trade names, their
Turn to page 10
Boehringer Hopes To Tap AbbVie’s ‘Humira Magic’
Boehringer Ingelheim and AbbVie Inc. have
launched a global collaboration to develop
two of the German group’s most advanced
biologic compounds in immunology, a
therapy field where the US-based group
has acquired extensive insight from its TNF
inhibitor Humira (adalimumab).
The investigative two compounds - BI
655066 and BI 655064 - are in various stages
of clinical development for a number of
immunology indications.
BI 655066, a monoclonal anti-IL-23 antibody
is the most advanced and will be tested in
psoriasis, Crohn’s Disease, and psoriatic arthritis.
BI 655064, a monoclonal anti-CD-40
antibody which is currently in Phase I being
studied for Lupus Nephritis, also has potential
for treating inflammatory bowel diseases such
Let’s get
Social
as Crohn’s Disease and colitis ulcerosa, the
companies announced March 7.
AbbVie Expertise Key
Both compounds have been discovered and
developed in-house by the family-controlled
German drug maker, at its Ridgefield
Connecticut labs in the US.
Turn to page 8
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contents/editor’s letter
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New Active Substance
Launches Plummet
Boehringer Hopes To Tap
AbbVie’s ‘Humira Magic’
Biotech IPOs: Will There Be
A March Miracle?
Amgen: Sandoz Seeks To
Circumvent Biosimilars Law
Schizophrenia Overview: Doctors
Highlight Pipeline Voids
PhRMA Condemns Medicare B Rx
Drug Payment Experiment
Medicare Chief: Engage With Us
On Payment Experiment
Zydus’ Humira Biosimilar:
The Story So Far In India
Sanofi Pasteur, Merck Part Ways
On European Vaccines Venture
PhRMA Chief: Time To Play Offense
On Price Debate
14A Life Sciences Fortuitous Opportunity:
NASA’s Twins Study
15Pharma’s Space Frontier:
Come On And Take A Free Ride
16R&D Bites
18$1.14bn For Xtandi Royalties: How
UCLA Cut Risk, Diversified Its Assets
19Using Patient Biology
To Shepherd Clinical Trials
19Has FDA Lost Its Grip?
The Amarin Deal
20Business Bulletin
20Policy & Regulation Briefs
21Expert View: Can Premium-Priced
Trulicity Prickle Victoza In India?
22Stockwatch: Pharmaceutical Fight Club
23Pipeline Watch
24Appointments
13Opdivo Reimbursement Rejected
In Scotland
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©Informa UK Ltd 2016: All rights reserved.
ISSN 0143 7690.
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March 18th 2016
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Eleanor Malone,
Editor,
Scrip Intelligence
2014 was an extraordinary year for pharma
and biotech. There were record numbers
of new drug approvals, biotech investment
boomed and the tax inversion gold rush
intensified M&A. Last year saw the biotech
boom continue for several months while
M&A activity was buttressed by Pfizer and
Allergan agreeing the biggest deal the
industry has ever seen towards the end of
the year. But everything on Earth is subject to
gravity, and what goes up must come down.
Sure enough, our headlines reflect a new
reality. Last year, the launch of new active
substances “plummeted” (see this week’s
cover story for Alex Shimmings’ analysis of
2015’s drug debuts).
In the second half of 2015, the decline
in biotech stock values began the “is the
bubble bursting?” debate, and this year,
biotechnology stocks have been “in freefall”,
as Mandy Jackson reports in her analysis of
the current IPO landscape on p3.
Even drug pricing, which has resisted the
law of gravity for so long (at least in the US), is
struggling to maintain its upwards trajectory,
and is coming under constant pressure
now from US politicians, pharmacy benefit
managers and competitive challenges alike.
On p6 Donna Young digs into the detail of the
US government’s redesign of the Medicare
Part B reimbursement system that is aimed at
removing incentives for doctors to prescribe
more expensive drugs. She reports on the new
president and CEO of PhRMA’s determination
to go on the offensive over the pricing debate,
which he argues unfairly characterizes the
pharma industry as adding to the cost of
healthcare, on p9. With this debate making the
headlines on a regular basis, the post-patent
cliff uplift that the sector has enjoyed for a
while now thanks to important new drug
launches feels vulnerable.
Gravity isn’t necessarily a bad thing for the
industry, though. Bubbles burst, but being
grounded enables us to distinguish true value
from hype, and build on stronger foundations.
Still, if that sounds depressingly mundane,
NASA is offering space on its rockets for
biomedical R&D projects looking to get away
from gravitational pull (p15). It might be your
best bet right now.
Astute readers may have experienced déjà vu when
reading this column last week. We apologize for any
confusion caused when we accidentally republished
an item from March 2014.
@scripnews
© Informa UK Ltd 2016
headline news
Biotech IPOs: Will There Be A March Miracle?
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Biotechnology stocks have been in a freefall
since the start of 2016, keeping firms with
plans for initial public offerings on the sidelines.
But with values up 5% since the start of this
month, will IPO hopefuls take advantage of a
Miracle March or will drug pricing concerns
again push share prices lower?
The Nasdaq Biotech Index (NBI) closed
March 7 with a 5.15% gain versus where
the index started the month, which feels
like it could be the start of a recovery after
investors watched the NBI fall 22.39%
between the start of January and the end
of February. However, the credit rating
agency Moody’s Investors Service lowered
its outlook for the global pharmaceutical
industry from positive to stable on March 3,
noting that drug makers are posting more
moderate price increases in response to the
ongoing debate about high prescription
medicine costs in the US.
Moody’s senior vice president Michael
Levesque said in a statement that the rating
agency’s pharma outlook changed, “because
of a modest reduction in our expectations for
the industry’s earnings growth.” Earnings are
expected to increase across the board by 3%
to 4% versus a prior forecast of 4% to 5%, due
to pharma companies’ less aggressive pricing
actions as well as foreign currency impacts
and slower than expected adoption of some
new products.
Griffin Securities analyst Keith Markey
noted in an interview with Scrip that, “As the
pressure builds on the industry, we’re going to
see greater and greater emphasis on the value
for the dollar. If there are great products, but
only a few people can afford them, they’re not
going to do very well.”
Markey said drug pricing has become
a political hot potato during an intensely
competitive US election cycle, with
presidential hopeful Hillary Clinton shining a
light on the issue in September. However, he
noted, there will always be pressure on the
cost of medicines when there’s a view that
certain products aren’t priced appropriately
relative to the value that they provide.
“If there’s something truly innovative,
and if it’s replacing an existing intervention,
whether it’s surgical or pharmaceutical, you
can look at the cost savings and use that as
a guide for what the pricing ought to be,”
Markey said, although he noted that different
organizations have different ideas about how
to value pharmaceutical innovation.
He noted that the biopharma industry and
health insurance provides are best-placed to
look at the value of new or existing medicines
versus the cost of – or lack of – available
Good news for venture capitalists as M&A
will help pharma companies grow in 2016
treatments. If the government steps in, “that’s
probably the worst case scenario at this point
in time,” he said. There’d be no flexibility in
negotiating outcomes-based pricing and
reimbursement agreements, which reward
drug makers for therapies that improve
outcomes and cut healthcare costs.
IPOs Wait For Good Signs
On the positive side, Levesque of Moody’s
noted that mergers and acquisitions will help
pharma companies grow in 2016, which is
good news for venture capitalists looking to
exit investments in private firms as well as for
stock market investors seeking big paydays
from publicly traded biotech holdings.
“Pharmaceutical companies will remain
active in the M&A market as they try to cut
costs, achieve greater scale and diversification,
and acquire pipeline drugs with high
potential,” Levesque said.
Moody’s issued its new outlook on global
pharma a day before Syndax Pharmaceuticals
Inc. launched the fifth biotech IPO of 2016 on
March 2 at $12 per share, which was below
the $14 to $16 offering price that Waltham,
Massachusetts-based Syndax proposed in
late February. The Syndax IPO, which grossed
$52.8m for the cancer drug developer,
was a big risk based on recent biotech IPO
performance.
Biotech IPOs that launched in 2015
provided such bad returns by year-end, and
stock prices for therapeutics companies
performed so poorly in January, that the
first four drug developers to price an IPO in
2016 didn’t do so until February and they
generated mixed results for investors.
Of those four offerings in February, the
gene editing company Editas Medicine Inc.’s
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share price was 122% above of its IPO value
as of March 4 and the Chinese immunooncology drug developer BeiGene Ltd. was
trading 35% above its US offering price.
However, Proteostasis Therapeutics Inc.,
AveXis Inc. and Syndax were trading 31%, 2%
and 1% below their IPO values, respectively,
noted the IPO-tracking firm Renaissance
Capital LLC.
Unfortunately, the Proteostasis, AveXis
and Syndax offerings mirror more closely the
performance of the 2015 IPO class, which
generated an average return of 3.6% versus
the offering price at year-end with last year’s
IPO companies generating a 21.3% loss on
average by the end of January 2016.
Recent biotech IPO performance has not
swayed new companies from announcing
their intentions to become publicly traded
entities, but some firms have withdrawn their
names from contention.
Hutchison China MediTech could become
the second Chinese immuno-oncology
company to list shares on the US stock market
in 2016 after BeiGene’s successful IPO. The
company said on March 4 that it may offer
6.1m American Depository Shares (ADSs) at
$16.33 each to raise $100m, but that was a
tentative price for the forthcoming offering.
On the other hand, PLx Pharma withdrew
its plan on March 7 to raise up to $68m to
commercialize a delayed-release aspirin
product. Also, there were no IPOs – not for
biotech or among companies in any other
industry – that were expected to price during
the week of March 7 to 11, according to
Renaissance Capital, suggesting that investors
in first-time offerings of any kind remain on
the sidelines.
[email protected]
March 18th 2016
3
headline news
Amgen: Sandoz Seeks To Circumvent Biosimilars Law
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Amgen Inc. has filed another lawsuit
involving the Biologics Price Competition and
Innovation Act (BPCIA) at the US District Court
for the District of New Jersey against Novartis
AG unit Sandoz Inc., accusing the biosimilar
maker again of violating certain aspects of the
law’s patent-dispute-resolution provisions –
commonly called the patent dance.
This suit involves Sandoz’s biosimilar of
pegfilgrastim, a product Amgen markets as
Neulasta.
Elaine Herrmann Blais, a partner and head
of litigation in the Boston office of Goodwin
Procter LLP, noted that Amgen’s latest
complaint does not allege patent infringement
claims, but rather seeks a declaration from the
court that Sandoz is wrong.
It also alleges and that Amgen would not
be limited to seeking reasonable royalties if it
later brings a patent infringement suit against
Sandoz concerning its pegfilgrastim product,
she pointed out.
Sandoz has indicated it does not intend
to follow the patent dance provisions and
has insisted Amgen file an immediate patent
infringement action before the conclusion
of the BPCIA dispute-resolution process and
has threatened to seek penalties under law if
the innovator failed to do so, the latter firm
contended in a complaint filed on March 4.
Sandoz asserted that Amgen must file its
patent infringement lawsuit by March 4 or
such lawsuit would be untimely and its patent
infringement damages would be limited to a
“reasonable royalty.”
Amgen, which insisted Sandoz was wrong
about having to file a patent infringement suit
by March 4, said it filed its action to protect
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March 18th 2016
its rights and to obtain an order compelling
Sandoz to comply with the BPCIA’s provisions.
The California biotech giant also disagreed
with Sandoz’s assertion that filing a
patent infringement lawsuit after March 4
deprived Amgen of its entitlement to other
infringement relief provided by the BPCIA,
such as a permanent injunction.
Amgen already is tied up in two other
lawsuits with Sandoz – one involving the
latter firm’s biosimilar of filgrastim, Zarxio
(filgrastim-sndz), which it wants the Supreme
Court to settle – and the other involving its
copycat of Enbrel, which also is before the
New Jersey district court.
Like the Enbrel biosimilar suit, Amgen
accused Sandoz in the latest case of
“piggybacking on the fruits” of the
innovator’s “trailblazing efforts” and of trying
to “once again” “reap the commercial benefits
provided to biosimilar manufacturers
under the BPCIA while seeking to avoid the
obligations” Congress established to protect
branded companies.
In the new lawsuit, Amgen noted the BPCIA
created an intricate and carefully orchestrated
set of procedures for biosimilar applicants
and reference product sponsors to engage
in a series of information exchanges and
good-faith negotiations between parties
before filing a patent infringement lawsuit –
provisions aimed at avoiding burdening the
courts and parties with unnecessary disputes.
The FDA accepted Sandoz’s 351(k)
biosimilars application for its version of
pegfilgratim this past October, although the
company didn’t reveal that action until a few
weeks later.
On Nov. 13, 2015, Sandoz provided
Amgen with a file transfer link to electronic
files in which the biosimilar firm said
constituted its application and information
relating to the manufacturing process for its
pegfilgrastim product.
Amgen said it provided Sandoz on Jan.
12 a list identifying two patents for which
the innovator believed a claim of patent
infringement could reasonably be asserted
against the pegfilgrastim biosimilar.
Sandoz argued in its Feb. 2 reply the
patents were “invalid, unenforceable or
will not be infringed by the commercial
marketing” of the biosimilar and said it no
longer wanted to follow the strictures of
the BPCIA – cutting the patent dance short
and telling Amgen to move forward with a
patent infringement lawsuit “Otherwise, the
penalty for an untimely suit – that the ‘sole
and exclusive remedy’ for any infringement be
limited to a ‘reasonable royalty’ – applies.”
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By refusing to participate in a “timely and
complete manner” under the BPCIA, including
by seeking to extinguish the innovator’s
ability to consider and respond to Sandoz’s
contentions about the patents the innovator
had “properly identified” and “entirely evading”
the negotiations, the biosimilar maker has
“repudiated” its obligations under the BPCIA,
Amgen charged.
After beginning the statutory exchange
process, Sandoz is unwilling to complete
the BPCIA’s procedures and has sought to
“circumvent” the law’s process by refusing
to participate in the patent dance and
threatening to seek penalties that limit
Amgen’s relief for infringement to a
reasonable royalty – rather than the full
complement of remedies available, the latter
company argued.
Amgen has asked the court to issue a
judgment declaring that that Sandoz failed to
comply with the “mandatory” requirements
of the BPCIA patent dispute resolution
provisions, and that its attempt to “waive”
the rest of the exchanges and negotiations
preceding the “immediate litigation” phase of
the law “means there can be no immediate
patent infringement action, Herrmann Blais
pointed out.
Amgen said that although it has not yet
filed an action for patent infringement, that
does not mean it is thereby barred from later
seeking the full scope of remedies available
for patent infringement claims, including lost
profits and injunctive relief, she explained.
Herrmann Blais noted Amgen also asked
for an order compelling Sandoz to comply
with the rest of the BPCIA patent dance, and
to compensate the innovator for “damages
incurred as a results of biosimilar maker’s
actions or inactions.
“As Amgen notes in its complaint, this is not
the first time a district court has been asked
to consider whether biosimilar applicants can
agree to immediate litigation on the patents
listed by a reference product sponsor, instead
of engaging in negotiations on which of the
listed patents will be the subject of the first
wave of immediate litigation contemplated
by the BPCIA,” said Alexandra Lu, an associate
in the litigation group at Goodwin Procter’s
Boston office.
Indeed, she said, the same question
also has been raised in two other lawsuits
pending at other district courts: Janssen
v. Celltrion at the US District Court for the
District of Massachusetts, and and Amgen
v. Hospira, at the US District Court for the
District of Delaware.
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headline news
Schizophrenia Overview: Doctors Highlight Pipeline Voids
The top unmet needs in schizophrenia drug
therapy are medicines for the management
of negative symptoms, new treatments for
refractory-positive symptoms and improved
tolerability of drug treatment, according to a
Datamonitor Healthcare survey of more than
200 psychiatrists.
Negative symptoms in schizophrenia
remain largely untreated, despite being
present in nearly 50% of patients and
despite the sizeable number of approved
antipsychotics available for the disease overall
– most of which focus on positive or cognitive
symptoms. This treatment gap was marked
as the greatest unmet need by 236 surveyed
physicians. Even with this need, the current
pipeline for new antipsychotics contains
few products specifically targeting negative
symptoms.
Schizophrenia presents itself in various
forms, with patients suffering different sets of
symptoms. Certain subtypes of the disease
are associated with negative symptoms,
such as avolition, blunted affect, and slower
movement patterns.
Minerva Neurosciences is one company
advancing development of a new drug, MIN101, specifically targeting negative symptoms
of schizophrenia. MIN-101, currently in
Phase IIb clinical trials, functions primarily by
targeting the 5-HT2A receptor and Sigma2 receptor as an antagonist. It is thought
that the blockade of 5-HT2A may improve
negative symptoms of schizophrenia by
cultivating mood without carrying significant
side effects. Minerva believes MIN-101 will
improve negative symptoms, cognitive
symptoms, and correct sleep abnormalities in
schizophrenia patients.
ITI-007 from Intra-Cellular Therapies and
encenicline from Forum Pharmaceuticals/
Mitsubishi Tanabe, both of which are in Phase
III trials, are two other candidates being
developed to help address negative and
cognitive symptoms.
ITI-007 also appears to address doctors’
concerns around improved tolerability
of drugs for schizophrenia. Intra-Cellular
Therapies reported positive Phase III data in
September 2015 for ITI-007, which showed a
potentially differentiated safety profile relative
to approved antipsychotic drugs. As such the
company is pursuing a first-line indication for
ITI-007, which combines serotonin 5-HT2A
receptor antagonism, dopamine receptor
phosphoprotein modulation (DPPM),
glutamatergic modulation and serotonin
reuptake inhibition in a once-daily pill.
Intra-Cellular reported that ITI-007 did not
differ significantly from placebo in terms
of safety, including motor, metabolic and
cardiovascular side effects associated with
other schizophrenia drugs. Sagient Research’s
BioMedTracker expects ITI-007 to reach the
market late in 2017 or early 2018 if the company
is successful in gaining market approvals.
Meanwhile, encenicline’s recently
discovered gastrointestinal safety issues
(noted in Alzheimer’s trials of the drug) could
pose a risk to its development program.
Positive symptoms of schizophrenia, such
as hallucinations and/or delusions, are more
widely treated by current therapies. However,
the issue of drugs for refractory patients was
among top concerns for doctors surveyed by
Datamonitor Healthcare.
The most commonly used option in
treatment-resistant patients is clozapine,
an atypical antipsychotic that improves
schizophrenia symptoms in patients who do not
respond adequately to standard antipsychotic
treatments. Nevertheless, Datamonitor
Healthcare analyst Ines Guerra highlighted that
while clozapine is a “useful therapeutic option,
the drug can cause severe neutropenia.” In
the US, clozapine-treated patients need to be
monitored and managed for severe neutropenia
events, under the Clozapine Risk Evaluation and
Mitigation Strategy (REMS) Program.
There are currently no late-stage pipeline
candidates that appear to have the potential
to alleviate refractory positive symptoms, but
between 10% and 30% of patients show little
symptomatic improvement after multiple
trials of typical antipsychotics.
Oral Therapies Lead Charge
Datamonitor Healthcare found that in every
surveyed market, the most commonly
prescribed treatments for acute schizophrenia
included oral formulations of olanzapine,
risperidone, and aripiprazole. However, of these
15 leading therapies, no single medication
is recommended for first-line use in the US,
the UK, Germany, Spain and Italy. This is
likely because of the lack of differentiation
between the clinical profiles of the available
antipsychotics.
To view a table online of all products in
clinical development for the treatment of
schizophrenia, Phase I to NDA submission, go to:
http://bit.ly/1Uwqoy7
[email protected]
Leading Schizophrenia Therapeutics
Drug Name
Company
Most Commom Therapeutic Role
Abilify
Otsuka/Lundbeck
Acute and maintenance treatment of schizophrenia Oral, tablets
Abilify Maintena
(aripiprazole)
Otsuka/Lundbeck
Acute and maintenance treatment of schizophrenia Intramuscular, long-acting
injection
Clozaril (clozapine)
Novartis
Fanapt
(iloperidone)
Vanda
Pharmaceuticals
Treatment-resistant schizophrenia, reduction in
risk of suicidal behavior in schizophrenia
Geodon/Zeldox
(ziprasidone)
Pfizer/Meiji Seika
Invega
(paliperidone)
J&J
in adults and adolescents
Invega Sustenna
J&J
injection
Latuda
(lurasidone)
Dainippon
Sumitomo
Lonasen
(blonanserin)
Dainippon
Sumitomo
Risperdal
(risperidone)
J&J
Risperdal Consta
(risperidone)
J&J
injection
Saphris/Sycrest
(asenapine)
Allergan/Lundbeck/
Meiji Seika
Seroquel
(quetiapine)
AstraZeneca/
Astellas
Zyprexa
(olanzapine)
Eli Lilly
Zyprexa Relprevv
Eli Lilly
injection
@scripnews
Administration
Oral, tablets
March 18th 2016
5
headline news
PhRMA Condemns
Medicare B Rx
Drug Payment
Experiment
The Pharmaceutical Researchers
and Manufacturers of America
(PhRMA) wasted no time in condemning
the Obama administration’s plans
to launch a new experiment testing
whether alternative payment designs
may lead to reducing Medicare Part
B expenditures, while preserving and
potentially even enhancing beneficiaries’
quality of care.
“Proposing sweeping changes to
Medicare Part B drug reimbursement
without thoughtful consideration
and stakeholder input is not the right
approach and puts Medicare patients
who rely on these medicines at risk,”
PhRMA spokesperson Allyson Funk told
Scrip in a statement.
She insisted the current drug
payment methodology for Part B, which
covers prescription medicines that are
administered in physician’s offices or
hospital outpatient departments, such as
cancer therapies, injectables antibiotics
and eye care treatments, is “an effective,
market-based pricing mechanism that
works to control costs.” But Patrick Conway,
chief medical officer at the Centers for
Medicare & Medicaid Services (CMS),
argued the current structure provides
“perverse incentives” that encourages
doctors to prescribe the most expensive
drugs over lower-cost products that are
just as effective.
Currently, Medicare Part B generally
pays physicians and hospital outpatient
facilities a drug’s average sales price
(ASP) plus a “statutorily mandated” addon of 6%.
But in a Federal Register notice posted
online on March 8, CMS contended the
ASP methodology “may encourage the
use of more expensive drugs because the
6% add-on generates more revenue for
more expensive drugs.”
“The Part B payment method provides
weak incentives for physicians to consider
value – that is choose the lowest cost
therapy to effectively treat a patient,”
the agency said in a separate document
posted on its website.
Read full story at: http://bit.ly/1U0HuFX
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6
March 18th 2016
Medicare Chief: Engage With Us
On Payment Experiment
Centers for Medicare & Medicaid Services
(CMS) acting administrator Andy Slavitt
entered the lion’s den on March 9 and
faced about 300 hundred drug company
executives and other healthcare stakeholders
at a meeting in Washington the day after
releasing a controversial proposal to overhaul
the way the government pays for outpatient
prescription medicines, which had some
industry leaders up in arms before it was even
officially revealed. But Slavitt was conciliatory,
declaring at the annual meeting of the
Pharmaceutical Research and Manufacturers
of America (PhRMA) that “I don’t think we feel
like we have the monopoly on good policy.”
He insisted, however, there was “nothing
we proposed to do or intend to do or
should do that, in any way, prevents a
patient from getting the prescription
medicine that they need.”
Doctors encouraged to prescribe
expensive drugs over lower-cost
comparators with same benefits
Slavitt said CMS’ March 8 proposal to test
whether alternative payment designs may lead
to reducing expenditures for Medicare Part B,
which covers prescription medicines that are
administered in physician’s offices or hospital
outpatient departments, such as cancer
therapies, injectables antibiotics and eye care
treatments, would allow the agency to engage
with stakeholders and the public and “invite
people” to look at six “substantive” ideas.
The centerpiece of the experiment involves
changing the Medicare Part B reimbursement
rate doctors and outpatient facilities are paid
for prescription drugs. Currently, the payment
covers a drug’s average sales price plus a
“statutorily mandated” add-on of 6%. But CMS
wants to test whether changing the add-on
payment to 2.5% plus a flat fee payment
of $16.80 per drug would strengthen the
financial incentive for physicians to choose
higher value drugs and improve quality.
CMS officials argued the current system
encourages doctors to prescribe the most
expensive drugs over lower-cost products that
are just as effective. But the plan was swiftly
condemned by the big brand-name drug
lobbying groups – with PhRMA warning that
making “sweeping changes” to the Medicare
Part B drug reimbursement rate “without
thoughtful consideration and stakeholder
input” would put beneficiaries “at risk.”
@scripnews
The Biotechnology Innovation Organization
said it was “gravely concerned” CMS’ proposed
model “threatens to disrupt the successful
reimbursement framework” already in place.
But Slavitt contended that “These are not
ideas we’ve made up.”
Rather, he said, the concepts in CMS’ Part B
payment proposal have been “long discussed”
and were “long-brought forward,” and should
help people to want to connect with the
agency – eventually getting to the “substance
of what will make good policy.”
“My ask of everyone is that we engage on
this together, and we engage on it seriously
and collaboratively,” the CMS chief declared.
Slavitt said the agency’s goal with the
Part B experiment is to determine what
works well and what doesn’t and “adjust.” He
acknowledged that before CMS could even
get the proposal out the door, there already
were efforts to stop it in its tracks.
Kenneth Frazier, chair and CEO of Merck &
Co. Inc. and PhRMA’s chair, said the industry
was concerned about CMS making a “major
shift in the healthcare delivery system.”
“People want to make sure we are thinking
about this very carefully,” Frazier said.
Frazier told Slavitt to expect to hear
“constructive reactions” from drug makers over
the next few weeks.
“Do I think we’ve thought of everything and
every consequence? Absolutely not,” Slavitt
responded. But he defended CMS’ actions –
insisting it is a “process that invites the most
public input possible.”
He reminded drug makers at the PhRMA
conference “We are in early innings still”
with the Part B payment experiment, which
actually won’t get underway until this fall,
with the second stage not launching until
early next year.
Slavitt admitted that often a “policy
that sounds great in Washington” may
actually end up being burdensome when
it’s put to the test in the real world, which
is why Slavitt said it’s important to
experiment with new models like CMS is
attempting to do with the Medicare Part
B program, rather than simply instituting
the plan. Slavitt said he believes industry
and government already are “past the point
of finding the big ideas” on payment and
reimbursement issues.
“We are at the really interesting and
difficult part of the nitty-gritty of rolling up
our sleeves and making the world better for
people,” he said.
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headline news
Zydus’ Humira Biosimilar: The Story So Far In India
Challenges
While Exemptia’s patient base may still be
relatively small compared with the patient
pool, expanding access in India for such
products, though, comes with significant
challenges given that only an estimated 400
singh_lens/shutterstock.com
One dose of AbbVie’s blockbuster biologic,
Humira (adalimumab), in the US equals
around six doses of Zydus Cadila’s cut-price
biosimilar version in terms of the cost of
therapy and the Indian firm’s product appears
to have triggered interesting shifts both in
treatment dynamics and the competitive
landscape on the domestic market.
Zydus Cadila’s Exemptia (adalimumab)
costs INR11,000-14,000 ($163.4-208) per dose,
a fraction of Humira’s international price,
estimated at around $1,000 per vial, and the
Indian firm now has around 2,000 patients
on the product since its debut in December
2014, it told Scrip.
Zydus had at the time of launch claimed
that Exemptia was a “fingerprint match” with
the originator product in terms of safety,
purity and potency.
Experts suggest that the relevance of
the biosimilar’s price advantage is probably
more important in an out-of-pocket market
like India, where physicians generally try to
economize and prescribe adalimumab for
around six months to bring down/control
the severity of the symptoms after which the
patient can be tapered off the biologic and
maintained on oral/conventional therapies.
“Physicians may want the patient to
continue on the product for longer but the
patient’s economic condition may not permit
that in India,” an industry expert told Scrip.
Significantly, the arrival of biosimilar
adalimumab is also believed to have
triggered price cuts in therapies such as
etanercept and infliximab – the latter is said
to have seen dramatic reductions in the
average monthly treatment costs over the
past 15 months, though specifics could not
immediately be got.
“In the last six months there has been a
reduction of about 40% in the prices of other
biologics,” Zydus Cadila said.
Earlier this year, competitor Torrent
Pharma had followed Zydus onto the
domestic market with its adalimumab
biosimilar (marketed as Adfrar). The product
is part of the biosimilars portfolio covered
under Torrent’s 2014 exclusive licensing
pact with the local firm Reliance Life
Sciences, wherein the latter was to develop
and supply these products to Torrent post
regulatory approvals.
top Indian physicians are said to be focused
on rheumatology as a discipline and they are
largely based in metro cities and Class A towns.
“There is the question of awareness
and access in terms of medical expertise.
Besides, unfortunately, though patients may
have medical insurance, typically in India,
insurance covers only in-patient treatments.
This is a chronic disease that has a significant
economic/health burden, but our insurance
system is not geared to support this,” the
expert added.
Zydus claimed Exemptia was a
‘fingerprint match’ in terms of
safety, purity and potency
Zydus, though, maintains that it is on
course to developing Exemptia into an
INR1bn brand in around three years. It is
believed to be experimenting with an equal
monthly instalment (EMI)-based financing
model for the product. The model has
currently been rolled out on a pilot basis,
though the absence of a “pre-defined hard
stop” for treatment adds to complexities of
expanding such models.
India has seen such EMI-based financing
models for hepatitis C therapies and in the
devices space, among others. Typically, under
such financing schemes, patients can stagger
payment of the actual therapy cost over a
specified period via EMIs – along the lines of
similar schemes for consumer durables.
Zydus had, at the time of launch, also
indicated that it was putting in a place an
Exemptia Care program, which aims to provide
important support and information regarding
access, adherence, awareness and help
patients to appropriately manage their disease.
@scripnews
Exemptia has been approved for the
treatment of auto immune disorders such
as rheumatoid arthritis, juvenile idiopathic
arthritis, psoriatic arthritis, ankylosing
spondylitis, ulcerative colitis and Crohn’s
disease in India.
Zydus, whose pipeline comprises 24
biosimilars under development including four
novel biologics, expects to take products such
as Exemptia to international markets.
“The plan is to launch all the molecules
first in India, then in the emerging markets
and finally selected molecules globally in
the more regulated markets (the US and
the EU). Three molecules are already in
global development for the more regulated
markets,” Zydus said.
On AbbVie’s reference to limited studies
with Exemptia in India, Zydus indicated that
its product has a finger print match with the
innovator product – one of the most difficult
things to achieve and that once achieved the
assumption generally is that all that has been
proven with the innovator brand should be
replicable with the fingerprint like biosimilar.
Zydus also said that its study was
statistically powered, significantly enough for
the regulator to give an approval.
The company added that it expects to
take its product to other markets and its
dossiers would be “robust” to withstand those
guidelines and pass through.
AbbVie had earlier noted that Exemptia’s
Phase III study included only 120 patients in
India and in a single indication, rheumatoid
arthritis. “As a result, it is unclear whether it is a
biosimilar by the standards of other regulatory
agencies, such as the FDA,’’ AbbVie said then.
Humira raked in 2015 revenues of $14bn
(+11.7%), accounting for more than half of
AbbVie’s $22.8bn in total sales for the year.
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March 18th 2016
7
headline news
Boehringer Hopes To Tap Abbvie’s ‘Humira Magic’
Boehringer Ingelheim says it now needs
a well-placed, experienced partner to
ensure that the medicines are developed
and commercialized as best and as quickly
as possible.
“We have entered this collaboration
to ensure that these two very promising
compounds can be progressed to benefit
all patients directly from the moment of
launch,” according to Jan Poth, who heads
immunology at Boehringer Ingelheim
“We have been active in immunology for
quite some time already but we don’t have any
product on the market yet so we don’t have a
commercial organisation for that therapeutic
area yet. AbbVie on the other hand has
extensive experience in the immunology field,”
Poth said in an interview, noting as an example
AbbVie’s blockbuster Humira, currently the
biggest selling drug in the world. “So they
are the ideal partner for us [and Boehringer
Ingelheim’s aspirations in immunology].”
“This collaboration positions BI 655066
as AbbVie’s lead investigational compound
in psoriasis, complementing our robust
immunology pipeline,” said AbbVie’s chief
scientific officer, Michael Severino. “Our
expertise in developing and commercializing
the world’s leading biologic, combined
with Boehringer Ingelheim’s clinical success
to-date will enable us to offer patients a
new treatment option with the potential to
meaningfully improve the standard of care,”
Severino said in a statement. More than 100
million people suffer from psoriasis, a chronic,
systemic, immune-mediated disease.
The two companies will work together in
clinical trials comprising various indications
for the two compounds. BI 655066 is entering
four Phase III trials in psoriasis, two of which
have already been initiated. “And probably in
the late 2016 or early next year, we will begin
Phase III trials [of BI 655066] in Crohn’s Disease.
This compound is currently in Phase II testing
for psoriatic arthritis,” Poth told Scrip. The last
of the four Phase III trials is expected to end in
late 2019 or early 2020, he added. BI 655066
is also in Phase II trialling for Ankylosing
Spondylitis as well as for asthma.
The new collaboration’s second focus, BI
655064, is a bit earlier in clinical development
and will start Phase II testing in Lupus Nephritis
within the next few months, Poth said.
Under the deal, AbbVie will make an initial
upfront payment of $595m. Boehringer
Ingelheim will be eligible to receive
additional development and regulatory
milestone payments and royalties on net
sales, the terms of which are not disclosed.
The partners hope BI 655066 can replicate
8
March 18th 2016
(Continued from page 1)
the positive data seen in a Phase II head-tohead psoriasis study that showed it having
superior efficacy over Johnson & Johnson’s
successful IL-12/IL-23 blocker Stelara
(ustekinumab). Last October, Boehringer
Ingelheim released nine-month data from
that study, dubbed NCT02054481, which
investigated the efficacy and safety of BI
655066 versus ustekinumab in 166 patients
and which after nine months showed 69%
of patients with moderate-to-severe plaque
psoriasis maintained clear or almost clear skin
as measured by the Psoriasis Area Severity
Index (PASI 90) with BI 655066, compared to
30% of patients on ustekinumab. Patients also
achieved this skin clearance significantly faster
- around eight weeks versus approximately 16
weeks, and for more than two months longer
than those on ustekinumab. Completely
clear skin (PASI 100) was maintained after
nine months in nearly triple the percentage
of patients on BI 655066 compared with
ustekinumab, or 43% versus 15%, Boehringer
Ingelheim said at the time.
“We hope to repeat these kinds of results
in Phase III and, based on that, expect these
compounds to have very good potential,”
Poth said.
The abnormal immune response in
psoriasis is driven by immune cells and
proteins that are released, known as cytokines.
A cytokine known as interleukin-23 (IL-23) is a
key driver in psoriasis, Poth explained.
AbbVie To Lead Regulatory Pathway
Asked about the likely regulatory pathway for
the two investigation biologics, BI 655066 and
BI 655064, Poth replied: “that’s a little down
the road but the plan is for AbbVie to lead
the registration process. The current timeline
foresees a launch of BI 655066 sometime in
late 2019 or early 2020.”
Boehringer Ingelheim has already had an
end-of-Phase II meeting with the FDA on
BI 655066.” The program has already been
evaluated by the FDA as well as the EMA
[European Medicines Agency] and we have
taken their advice into account with these
coming Phase III studies,” he said. Eventual
commercialization of the two compounds will
be done solely by AbbVie.
The immunology space is particularly fertile
for me-too drug and biologic development.
With multiple, relatively common diseases
including rheumatoid arthritis, psoriasis,
ankylosing spondylitis and inflammatory
bowel disease sharing the same or similar
biological pathways, immunology products
like AbbVie’s Humira have become megablockbusters.
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@scripnews
Sanofi Pasteur,
Merck Part Ways
On European
Vaccines Venture
retrorocket/shutterstock.com
Sanofi Pasteur MSD - the joint venture in
Europe between Sanofi SA’s vaccine arm and
Merck & Co – is ending after 22 years as the
duo believes they can better manage their
product portfolios independently.
Founded in 1994 and owned 50/50 by
the French and US drugmakers, Sanofi
Pasteur MSD was formed to combine their
geographic footprints and vaccines offerings.
It had sales of €824m in 2015, but revenues
have flattened recently.
The companies on March 8 said
the decision to dissolve their vaccines
partnership reflected changing times
in international markets and within the
companies themselves.
“Merck and Sanofi have reviewed their
strategic priorities for vaccines operations and
determined that operating independently
would benefit both by giving them better
control and flexibility, execute more efficiently,
accelerate growth within their businesses and
optimise global access to their vaccines,” Merck
& Co spokesperson Lainie Keller told Scrip.
Reflects New Sanofi CEO’s Priorities
The arrival of Sanofi’s new chief executive
Olivier Brandicourt has also played a part.
The French executive, who is reshaping
France’s biggest pharmaceuticals group,
has been in the role less than a year but
served notice last November that its vaccines
business was a core activity. Sanofi Pasteur
believes its experience developing Dengvaxia,
the first vaccine to prevent dengue fever, as ➤
headline news
well as vaccines against Chinese encephalitis
and yellow fever, gives it clear competitive
advantages going forward.
The decision to dissolve the
vaccines partnership reflected
changing times in international
markets and within the
companies themselves
Asked by Scrip whether Brandicourt’s plans
for the overall group were the catalyst for the
decision, spokesperson Alain Bernal replied: “The
decision was taken, it is true, at a point where
we at Sanofi are looking for more simplification
and clarity within the organization, so it should
be seen in conjunction with optimizing our
vaccines businesses, but I don’t think one thing
triggered the other.”
Bernal said each company in the joint
venture now had adequately large vaccine
portfolios to proceed alone.
“The joint venture had a very good
rationale when formed, and was very
successful. Now, not all Sanofi Pasteur MSD
products are being promoted at the level
that they could or should be, however, so
customers are not getting the optimum
options for our respective vaccines.
Separating should improve business for each
of the companies,” Bernal said.
Merck and Sanofi said they would integrate
their respective European vaccines businesses
into their existing operations, independently
manage their product portfolios and pursue
distinct growth strategies.
“We understand that one time cost of
restructuring for Sanofi should be around
€100m, with eventual revenue synergies of
€60m driven by Sanofi being able to provide
more sales effort behind their own products,”
commented analysts at Credit Suisse in a
note. They added that “Merck should see a
small boost to their revenues as they begin
to book sales for their own vaccines, but this
is expected to generally be offset by loss of
equity income from the JV.”
Merck will create a new vaccine division for
Europe, located in Lyon, France, the same city
that Sanofi Pasteur has its vaccines base.
Both Sanofi Pasteur and Merck said they
intend to keep investing in vaccines R&D and
will continue efforts to commercialize Vaxelis,
a combination vaccine designed to protect
infants and toddlers against diphtheria,
tetanus, pertussis, hepatitis B, poliovirus types
1, 2 and 3, and invasive disease caused by
Haemophilus influenzae type B, giving it the
unwieldy nickname DTaP5-IPV-Hib-Hep.
Sanofi Pasteur and Merck said they will
ensure that any impact on employees
as a result of the proposed changes to
the business model “will be managed
responsibly. We are also focused on a
smooth and orderly transition while
achieving our public healthcare goals
and upholding our commitments to our
customers and business partners.”
Sanofi Pasteur and Merck expect dissolution
of their joint venture to complete by the end
of 2016.
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PhRMA Chief: Time To Play Offense On Price Debate
Drug makers have played defense long
enough in the debate over skyrocketing
prices of medicines and it’s time to go
on the offense and drive the discussion,
declared the new president and CEO of the
Pharmaceutical Research and Manufacturers
of America (PhRMA). Stephen Ubl asserted
the debate over drug prices in the US has
largely been “myopic and misinformed.”
It’s myopic, he said during a March 10
address at PhRMA’s annual meeting in
Washington, because it focuses on a “small”
share of healthcare spending and “not the
true cost driver, chronic disease, which is 80%
of US healthcare spending.”
Ubl noted the lion’s share of healthcare
costs are being borne in the institutional
settings, like hospitals, skilled nursing facilities
and physician office visits, where he insisted
“Our products stand the best chance of
ameliorating those costs.”
Ubl reverberated what’s become PhRMA’s
standard argument – the debate over drug
prices “ignores the value our products bring to
patients, the healthcare system and the broader
economy” – pointing to hepatitis C medicines,
which have been at the center of much of
the firestorm, as actually avoiding costly
complications, like liver disease or transplants,
and therefore saving the system money.
Value, he charged, is “barely a footnote.”
Ubl pointed to the tweet sent out last
September by former Secretary of State and
presidential candidate Hillary Clinton about
her plan to take on “price gouging, which
led to a $132bn drop in market cap in the
industry, as how vulnerable drug makers are
to the debate over the costs of medicines.
But Ubl argued “the debate is
misinformed because it focuses on list prices
and ignores increasingly consolidated and
sophisticated purchasers with enormous
marketplace leverage.”
‘Critics are basing all of
their policy solutions on
the anomaly’
He contended that “critics are basing all
of their policy solutions on the anomaly”
or 2014, when there were record FDA
approvals, a Medicaid expansion and the
entrance to the US market of new, and
expensive, hepatitis C medicines, “and not
the long-term trend.”
Ubl criticized the Centers for Medicare &
Medicaid Services’ proposal to overhaul the way
the government pays for outpatient prescription
medicines as “sweeping” and radical.
“This proposal would apply to vast
majority of the country, violating definition
of demonstration and the spirit of the
authority outlined in the statute,” Ubl said,
taking more of a hard-line tone than PhRMA’s
@scripnews
outgoing chair, Kenneth Frazier, CEO of
Merck & Co. Inc.,took the day before. “It
would usher in a new era of government
deciding what seniors can get. We believe
these are the wrong ways to solve the
healthcare cost problem.”
The new PhRMA chief, who stepped in to
John Castellani’s shoes this past December, said
“No one should doubt our resolve to fight price
controls in whatever shape they may take.”
“We know from experience,” he said,
“mandating prices leads to reduced access
and choice for patients.”
At PhRMA’s conference, Ubl also outlined
a new policy framework, which he said
consisted of four commonsense proposals:
modernizing the FDA; moving towards valuebased healthcare; engaging patients; and
addressing market distorting policies.
“Now is the time for PhRMA to play a
leadership role in advancing pragmatic, proconsumer policies that enhance the private
market and address costs holistically,” he said.
Also at the meeting, the board elected
its new directors, naming Biogen Inc. CEO
George Scangos as the lobbying group’s new
chair, succeeding Frazier.
Joaquin Duato, worldwide chair of
pharmaceuticals at Johnson & Johnson
Inc., also was voted chair-elect and Joseph
Jimenez, CEO at Novartis AG, assumed the
role of board treasurer.
[email protected]
March 18th 2016
9
headline news
New Active Substance Launches Plummet
mechanisms of action, the companies which
have launched them, the diseases they are
launched for, and the country and month
of first launch. Also noted is an indication of
whether or not they have received orphan
drug status, and whether or not they can be
considered novel in terms of whether a drug
with the same mechanism(s) is already on
the market.
These are some of the key metrics by which
to measure pharma’s R&D performance over
the year. Arguably for innovation, the most
important is the number with previously
unseen mechanisms of action, and here
the list makes for encouraging reading. An
impressive 14 of the NASs listed are first-inclass products, up from 12 (19.4%) in 2014
and therefore making up an even greater
percentage of the whole at 30.4%.
Orphans
One striking feature of the 2015 NAS list is how
many of the drugs which feature are orphans:
at 24 this was more than half. The final column
in the NAS table shows (see p11 & 12) whether
or not each of the NASs has orphan drug
status in at least one market for at least one
condition (it may not always be the country/
disease for which it received its first launch,
although this is mainly the case). A comparison
with recent years shows a dramatic increase
in the proportion of NAS launches with an
orphan drug status, showing a real shift in
drug development towards rare diseases.
Interestingly a large proportion of these are
for cancer indications (particularly multiple
myeloma) rather than the relatively easier-todevelop enzyme replacement therapies.
Company Performance
Once again, Novartis led the way with four
NAS first launches, and in 2015 the Swiss firm
shared top-billing with Allergan (it was with
Merck & Co and Eli Lilly the year before). But
Merck still did well in 2015 with three NAS
launches to its name. Indeed, each of the top
10 companies managed at least one launch
last year. But six of them were outplayed
by relative minnow Alexion, which enjoyed
a stellar year with two product launches,
both in its core area of expensive enzyme
replacement therapies. Early sales data have
been disappointing, though.
One of the most notable features of the
list is the further evidence it provides that
the revolution in cancer R&D is now bearing
NAS fruit. In 2014, products in the oncology
area accounted for 29.3% of drugs in the
pipeline, but only 14.5% of NAS launches. In
the year just closed, this gap had narrowed
10 March 18th 2016
(Continued from page 1)
at 30.4% and 28.2%, respectively. Thirteen
novel anticancers made their market debuts
during 2015, making this the most successful
therapeutic group by some way. And when
compared with oncology performance for the
past 15 years a clear trend can be discerned.
Five of the new anticancers are first-inclass products, and three of these also fit into
the rapidly expanding immuno-oncology
area. These include AbbVie and BristolMyers Squibb’s Empliciti (elotuzumab), the
first SLAMF7 antagonist. It’s one of nine
monoclonal antibodies on the list this year,
four of which are for cancer. SLAMF7 is a
CD2-like receptor involved in the activation
of cytotoxic cells, and the drug was launched
for the treatment of multiple myeloma.
In another first for multiple myeloma,
Genmab and Johnson & Johnson’s Darzalex
(daratumumab), the first CD38 antagonist,
was launched in the US, while the final
immuno-oncology MAb anticancer NAS
on the list is United Therapeutics’ Unituxin
(dinutuximab). This chimeric MAb targets
ganglioside antigen GD2 in the treatment
of pediatric Neuroblastoma, and has orphan
drug designation in both the EU and the US.
By contrast, there were far fewer antiinfectives hitting the pharmacies for the first
time last year – eight, compared with 21 in the
previous 12 months. But this was partly due
to the previous year’s HCV bubble, while 2015
was also light on new vaccine introductions.
There is only one first-in-class anti-infective
this year, and this is just a component of
an antibiotic combination. AstraZeneca
and Allergan added the novel specific
lactamase A and C inhibitor avibactam to
the previously-marketed cephalosporin
ceftazidime to form Avycaz for abdominal
and urinary tract infections.
And it was yet another disappointing year
for neurologicals. Despite being once again
the second-largest area in terms of number of
pipeline products, it fared poorly in delivering
just two new drugs to the market, continuing
a run of poor years for this difficult area.
The cardiovascular class performed better.
Two new PCSK9 inhibitors, Regeneron/
Sanofi’s Praluent (alirocumab) and Amgen’s
Repatha (evolocumab), reached the market
for hypercholesterolemia, with Praluent just
pipping its rival to the market after a very
close race. These injectable therapies are now
at the forefront of pricing and reimbursement
battles, a reminder if any were needed that
getting a product to market is not the final
hurdle to market success.
Also boosting the year’s tally to five,
and keeping the cardiovascular NAS
@scripnews
output relatively steady over the years,
were Boehringer Ingelheim’s Praxbind and
Novartis’s Entresto. Praxbind (idarucizumab)
is the first specific reversal agent for an
oral anticoagulant, in this case Boehringer
Ingelheim’s Pradaxa (dabigatran etexilate)
in cases where surgery is required or
uncontrolled bleeding occurs. The company
expects Praxbind to be used minimally,
but its existence should boost Pradaxa’s
use, as doctors will be more confident
using it knowing its effect can be reversed
when necessary. Entresto contains
the widely-prescribed angiotensin II 1
antagonist valsartan along with new drug
sacubitril and is an important improvement
in the treatment of symptomatic chronic
heart failure.
Other novel entries
The respiratory arena has not benefitted
from much in the way of new mechanistic
approaches in recent years, but in 2015
GlaxoSmithKline produced Nucala
(mepolizumab), the first interleukin-15
antagonist to reach the market. This is the first
of a new wave of products focusing on severe
refractory eosinophilic asthma. Another novel
NAS MAb which targets an interleukin, this
time 17A, Novartis’ Cosentyx (secukinumab)
was one of the Japanese first launches,
debuting there back in January 2015.
Another notable entry is Sprout’s
(Valeant’s) Addyi (flibanserin), which gained
approval at the third attempt for acquired
generalized hypoactive sexual desire disorder
in premenopausal women. But side-effect
limitations and a lack of marketing mean that,
far from being the “female Viagra,” the drug
has thus far been a commercial flop.
One thing that hasn’t changed over the
years is the US’s dominance of first launches.
It was the market of choice for 29 of the
NASs, well over half at 63%, and up from
2014’s 56%. Japan again performed well, its
eight launches this year beating the whole
of Europe combined; its recent push to
accelerate approval timelines is having the
desired effect. Within Europe, Germany was
the most popular European market for a first
launch, despite some companies’ ongoing
reimbursement problems there.
[email protected]
With thanks to Ian Lloyd senior director for
Citeline’s Pharmaprojects for help in compiling,
refining and analysing the NAS list.
Click here to access the full version of this story,
including interactive charts and tables.
headline news
Table 1: New Active Substance Launches 2015
Generic Name
Trade Name
Company
Indication
Mechanism Of Action
Country Of
First Launch
Month Of First
Launch? ↕
First In
Class?
Orphan Drug
Status?
afamelanotide
Scenesse
Clinuvel
Erythropoetic protoporphyria
Melanocyte stimulating
hormone A receptor agonist
Italy and
Switzerland
July
Yes
Yes
alipogene
tiparvovec
Glybera
uniQure/Chiesi
Lipoprotein lipase deficiency
Lipase clearing factor
stimulant
Germany
September
No
Yes
alirocumab
Praluent
Regeneron/Sanofi
Heterozygous familial
hypercholesterolemia & mixed
dyslipidaemia
PCSK9 inhibitor
USA
July
Yes
No
anthrax immune
globulin, Emergent
Anthrasil
Emergent BioSolutions
Anthrax infection
Immunostimulant
USA
September
No
Yes
asfotase alfa
Strensiq
Alexion
Perinatal, infantile and
juvenile-onset
hypophosphatasia
Alkaline phosphatase
stimulant
Japan
August
Yes
Yes
avibactam* +
ceftazidime
Avycaz
AstraZeneca/Allergan
Complicated abdominal and
urinary tract infections
Lactamase A/C inhibitor, Cell
wall synthesis inhibitor
USA
April
Yes
No
brexpiprazole
Rexulti
Otsuka
Major depressive disorder and
schizophrenia
Dopamine D2/D3 receptor
agonist, 5-HT1A receptor
agonist, 5-HT2A receptor
antagonist
USA
November
No
No
cangrelor
tetrasodium
Kengrexal
The Medicines
Company
Adjunctive therapy to
percutaneous coronary
intervention
Purinoreceptor P2Y12
antagonist, Platelet
aggregation inhibitor
EU and USA
September
No
No
ceftolozane
sulfate** +
tazobactam
Zerbaxa
Cubist/Merck & Co
Complicated,intra-abdominal
& urinary tract infection
Cell wall synthesis inhibitor,
Lactamase inhibitor
USA
February
No
No
chidamide
Epidaza
Shenzhen Chipscreen
Biosciences
Peripheral T-cell lymphoma
Histone deacetylase inhibitor
China
January
No
Yes
cobimetinib
Cotellic
Exelixis/Roche
Melanoma
MEK inhibitor
USA
November
No
Yes
daratumumab
Darzalex
Genmab/Johnson &
Johnson
Multiple myeloma
CD38 antagonist; Anticancer
immunotherapy
USA
November
Yes
Yes
deoxycholic acid
Kybella
Kythera (Allergan)
Submental fat reduction
Membrane integrity inhibitor
USA
June
No
No
dinutuximab
Unituxin
United Therapeutics
Neuroblastoma
Ganglioside antigen GD2
antagonist, Anticancer
immunotherapy
USA
October
Yes
Yes
DTP + polio vaccine,
Kitasato Daiichi
Sankyo
Squarekids
Daiichi Sankyo
Pertussis, diphtheria, tetanus
and poliomyelitis prophylaxis
Immunostimulant
Japan
December
No
No
elotuzumab
Empliciti
AbbVie/Bristol-Myers
Squibb
Multiple myeloma
SLAMF7 antagonist; Anticancer
immunotherapy
USA
December
Yes
Yes
eluxadoline
Viberzi
Furiex (Allergan)
Diarrhoea-predominant
irritable bowel syndrome
Opioid mu receptor agonist,
Opioid delta receptor
antagonist
USA
December
No
No
erismodegib
Odomzo
Novartis
Basal cell carcinoma
Hedgehog pathway inhibitor
USA
October
No
Yes
evolocumab
Repatha
Amgen
Heterozygous familial
hypercholesterolemia & clinical
atherosclerotic cardiovascular
disease
PCSK9 inhibitor
UK and USA
September
No
Yes
flibanserin
Addyi
Sprout
Pharmaceuticals
(Valeant)
Acquired generalized
hypoactive sexual desire
disorder in premenopausal
women
5HT1A receptor agonist,
5-HT2A receptor antagonist,
Dopamine D4 receptor agonist
USA
October
Yes*****
No
idarucizumab
Praxbind
Boehringer Ingelheim
Anticoagulant reversal
Chelating agent
USA
October
No
Yes
isavuconazonium
chloride
Cresemba
Basilea/Astellas
Invasive aspergillosis &
mucormycosis
Cell wall synthesis inhibitor
USA
April
No
Yes
Turn to page 12
@scripnews
March 18th 2016
11
headline news
ixazomib citrate
Ninlaro
Takeda
Multiple myeloma
Proteasome inhibitor,
Transcription factor NF-kappaB
inhibitor
USA
December
No
Yes
lenvatinib
Lenvima
Eisai
Metastatic thyroid cancer
VEGFR-1,2,3 tyrosine kinase
inhibitor, FGF receptor 1,2,3,4
tyrosine kinase inhibitor,
Platelet-derived growth factor
receptor beta kinase inhibitor,
RET tyrosine kinase inhibitor,
C-kit inhibitor
USA
February
Yes******
Yes
lumacaftor*** +
ivacaftor
Orkambi
Vertex
Cystic fibrosis
CF transmembrane
conductance regulator agonist
USA
September
No
Yes
lusutrombopag
Mulpleta
Shionogi
Thrombocytopenia
Thrombopoietin agonist
Japan
December
No
No
mepolizumab
Nucala
GlaxoSmithKline
Severe asthma
Interleukin 5 antagonist
USA
December
Yes
Yes
myoblast cell
therapy, ACT
HeartSheet
Terumo
Congestive heart failure
Not applicable
Japan
September
No
Yes
necitumumab
Portrazza
Eli Lilly
Non-small cell lung cancer
EGFR antagonist
USA
December
No
Yes
nemonoxacin
Taigexyn
Warner Chilcott/
TaiGen
Community-acquired
pneumonia
DNA topoisomerase II/IV
inhibitor
Taiwan
December
No
No
omarigliptin
Marizev
Merck & Co
Type 2 diabetes
Dipeptidyl peptidase 4 (DPP
IV) inhibitor
Japan
December
No
No
osimertinib
Tagrisso
AstraZeneca
Non-small cell lung cancer
EGFR kinase inhibitor
USA
November
No
Yes
palbociclib
Ibrance
Pfizer/Amgen
Breast cancer
Cyclin-dependent kinase 4/6
inhibitor
USA
February
Yes
No
panobinostat
Farydak
Novartis
Multiple myeloma
Histone deacetylase inhibitor
USA
March
No
Yes
patiromer
Veltassa
Relypsa
Hyperkalaemia
Potassium antagonist
USA
December
Yes
No
polmacoxib
Acelex
Aestura
(AmorePacific)/
CrystalGenomics
Musculoskeletal and
osteoarthritic pain
Cyclooxygenase 2 inhibitor,
Carbonic anhydrase inhibitor
South Korea
September
No
No
rolapitant
Varubi
OPKO Health/Tesaro
Chemotherapy-induced nausea
and vomiting
Neurokinin 1 receptor
antagonist
USA
November
No
No
rotavirus vaccine,
Bharat
Rotavac
Bharat Biotech
Rotavirus infection prophylaxis
Immunostimulant
India
March
No
No
sacubitril**** +
valsartan
Entresto
Novartis
Chronic heart failure
Angiotensin II 1 antagonist,
Membrane metallo
endopeptidase inhibitor
USA
July
No
No
safinamide
mesylate
Xadago
Newron/Zambon
Parkinson’s disease
Monoamine oxidase B
inhibitor, Sodium channel
antagonist, Calcium channel
antagonist, Glutamate release
inhibitor, Dopamine reuptake
inhibitor
Germany
May
No
No
sebelipase alfa
Kanuma
Synageva BioPharma
(Alexion)
Lysosomal acid lipase
deficiency
Lysosomal acid lipase
stimulant
Germany
October
Yes
Yes
secukinumab
Cosentyx
Novartis
Psoriasis & psoriatic arthritis
Interleukin 17A antagonist
Japan
January
Yes
Yes
talimogene
laherparepvec
Imlygic
Amgen
Melanoma
Granulocyte macrophage
colony stimulating factor
agonist, Anticancer
immunotherapy
USA
November
No
Yes
trelagliptin
Zafatek
Takeda/Allergan
Type 2 diabetes
Dipeptidyl peptidase 4 (DPP
IV) inhibitor, Insulin
secretagogue
Japan
May
No
No
vonoprazan
fumarate
Takecab
Takeda/Otsuka
Ulcer and oesophagitis
Potassium-competitive acid
antagonist
Japan
February
No
No
9-valent HPV
vaccine, Merck
Gardasil 9
Merck & Co
Human papilloma virus
infection prophylaxis
Immunostimulant
Canada
April
No
No
Source: Scrip Intelligence, Citeline’s Pharmaprojects
*avibactam is the NAS here **ceftolozane sulfate is the NAS here ***lumacaftor is the NAS here ****sacubitril is the NAS here *****Dopamine D4 antagonist is the novel mechanism here
******FGF-2 and -4 tyrosine kinase inhibition are the novel mechanisms here ↕Some months may be approximations
12 March 18th 2016
@scripnews
headline news
Opdivo Reimbursement Rejected In Scotland
Bristol-Myers Squibb’s skin cancer therapy,
Opdivo (nivolumab), has been rejected for
use on the Scottish National Health System
– an unusual decision considering the drug’s
recent approval for use in England and Wales.
The Scottish Medicines Consortium issued
guidance not recommending the use of
Opdivo – a PD-1 immune checkpoint inhibitor,
a new class of cancer medicines – as a
monotherapy for the treatment of advanced
(unresectable or metastatic) melanoma in
adults. The health technology appraisal body
said it was disappointed about returning a
negative verdict, but said “weaknesses” in the
health economic case presented by BMS led
to “considerable uncertainty” about the drug’s
cost-effectiveness.
However, BMS’s product was accepted,
uncharacteristically quickly, by the SMC’s
neighbor NICE for use on the NHS in England
and Wales in January this year. It is not
uncommon for the two devolved HTAs in
Britain to come to opposing verdicts for new
products and in the past the groups have
returned differing opinions on the use of a
number of expensive new cancer therapies.
Nevertheless, the SMC has usually been
more flexible for novel oncology products,
approving medicines that NICE has rejected.
For example, in December 2014 the SMC
reimbursed two cancer products that NICE
had already turned down – Eli Lilly’s Alimta
(pemetrexed)as a monotherapy for the
maintenance treatment of locally advanced
or metastatic non-small cell lung cancer;
and Celgene’s Imnovid (pomalidomide) in
combination with dexamethasone for the
treatment of adult patients with relapsed and
refractory multiple myeloma. Furthermore,
in April 2015, Scotland gave the green light
to three anticancers that England had at the
time rejected – Ariad’s Iclusig (ponatinib),
Boehringer Ingelheim’s Vargatef (nintedanib)
and Bayer’s Stivarga (regorafenib). Some of
these products have since been accepted for
reimbursement by NICE.
The assessment for Opdivo in Scotland also
included views from a Patient and Clinician
Engagement (PACE) meeting, but doctors’
opinions emphasizing the need for new
therapies like Opdivo, which have fewer side
effects and can be used in patients who don’t
have BRAF mutations, were not able to sway
the SMC.
A spokesperson for the SMC told Scrip that
BMS’s submission for Opdivo contained a
complex economic model involving treatment
naïve and pre-treated melanoma patients with
more than one possible comparator. “There
were a number of uncertainties in the analyses
and some assumptions, for example around
treatment duration, that the committee felt
were unlikely to reflect clinical practice,” the
SMC said.
BMS said it presented the same evidence
to both NICE and the SMC, including the
same drug list price that NICE found costeffective. In England Opdivo costs £439
per 4ml vial and £1,097 per 10ml vial,
excluding VAT and any local procurement
discounts. NICE’s appraisal committee in
January decided that the incremental cost
effectiveness ratio for the drug, compared
with BMS’ Yervoy (ipilimumab), Roche’s
Zelboraf (vemurafenib) and Novartis’ Tafinlar
(dabrafenib), would be less than £30,000 per
quality adjusted life year gained.
In Scotland BMS now has the option to
submit further data analysis to the SMC for
consideration.
[email protected]
SPONSORED BY
CATEGORY SPONSORED BY
HUYA BIOSCIENCE’S BEST
NEW DRUG AWARD
WINNER:
NOVARTIS’S COSENTYX
This human monoclonal antibody is the first and only approved IL-17A inhibitor for plaque psoriasis, offering an important
new treatment option, and a better chance of achieving clear skin. The judges said: “IL-17A has been an interesting target
in psoriasis and this drug has shown selective binding that has translated into excellent clinical activity. The superiority
of Cosentyx (secukinumab) against two of the most widely used drugs is impressive and the long-term data confirm its
potential to transform treatment.”
“
Novartis is honored that Cosentyx has been named the Best New Drug of 2015. This award speaks to a turning point
for psoriasis patients, as Cosentyx is the first and only approved treatment targeting the IL-17 pathway, which plays a
key role in the development of plaque psoriasis. Nearly half of all psoriasis patients have not found relief from previously
existing therapies with the condition seriously impacting their everyday lives, both physically and psychosocially.
Cosentyx truly provides a better chance of achieving clear skin and improving the quality of life of psoriasis patients.
@scripnews
“
Vasant Narasimhan, Global Head of Development, Novartis Pharmaceuticals
March 18th 2016
13
headline news
A Life Sciences Fortuitous Opportunity: NASA’s Twins Study
While the goal of the yearlong mission
aboard the International Space Station (ISS)
involving US astronaut Scott Kelly and his
Russian counterpart cosmonaut Mikhail
Kornienko, who both returned to Earth on
March 2, was intended to examine the effects
of microgravity on the human body with the
aim of reducing the health risks on future
crewmembers, NASA serendipitously fell into
a fortuitous situation to study spaceflight
at the molecular level, potentially providing
the life sciences sector a wealth of data – an
opportunity that may not come around again
for quite some time, if at all.
Kelly, of course, just happens to have an
identical twin brother, Mark, who also is an
astronaut – a situation never before seen at
NASA or any other space agency.
The idea of studying one twin in space and
the other on the ground came about more by
happenstance than a planned situation when
Scott Kelly was selected for the ISS mission,
said John Charles, chief scientist of NASA’s
Human Research Program (HRP).
Had anyone else been selected, “we
wouldn’t be having this discussion” and there
would be no Twins Study, Charles told Scrip.
But once the suggestion was made in 2012
and the Kelly brothers accepted, there was
a “very big flurry of activities,” and Charles
quickly found some HRP funding and put
together a research solicitation, getting
40 responses right away, with 10 principal
investigators and their proposed projects
ultimately selected.
What surprised Charles, he said, was the fact
that five of those 10 investigators had never
before worked with NASA and previously
never considered how the US space agency
was relevant to their genetic research.
“And those have now been some of the most
enthusiastic participants,” he declared, although
he added that most “everybody is enthusiastic
when you’re on a spaceflight mission.”
The twins experiment has allowed NASA
to connect with “a whole new community of
investigators who can give us new insights
that we need to continue the work that we’re
doing of mitigating the risks of astronauts of
long-duration space flights beyond low-Earth
orbit,” Charles said.
Being able to include the Twins Study
data in the efforts of the Precision Medicine
Initiative, which is being led by the National
Institutes of Health, could provide “great
interest” for drug companies’ research and
development, Roberts told Scrip.
He said CASIS would like to work with
pharmaceutical companies to replicate the
Twins Study to perform experiments using
models with identical mice or flat worms in
precision medicine-type experiments with the
goal of drug discovery and development.
“You can perform a lot of the same tests to
understand how they are responding to the
microgravity environment with prolonged
exposure to that environment over time,”
Roberts said.
He said he thought the Twins Study also
could have implications for Obama’s and
Vice President Joe Biden’s Cancer Moon Shot
Initiative, given the examination of Scott
Kelly’s long-term radiation exposure that will
be examined over time from his year in space,
which started on March 27, 2015.
Precision Medicine
The Experiments
Even though it’s a very small cohort of two
men, the Twins Study data could wind up
playing a role in President Barack Obama’s
Precision Medicine Initiative, he said.
“That is one of the major reasons we
embarked on this study is to understand
exactly how we can use precision medicine
Among the 10 Twin Study investigations is
one being conducted by researchers from the
University of California at San Diego (UCSD) and
Dana-Farber/Harvard Cancer Center in Boston
in conjunction with NASA’s cardiovascular
and nutritional biochemistry labs to examine
the metabolomic and genomic markers of
14 March 18th 2016
in making more efficient and effective plans
for these long duration plans beyond the lowEarth orbit,” Charles said.
Michael Roberts, deputy chief scientist at
Center for the Advancement of Science in
Space Inc. (CASIS), which manages the ISS
US National Laboratory, said he’d like to see
an astronaut cohort be part of the Precision
Medicine Initiative, “because even though it’s
a small sample size, you have a segment of
the population that goes from being perfectly
healthy to manifesting some aspects of disease
as a result of their exposure to microgravity” –
an environment whose effects on physiology
can mimic the process of aging and some
human conditions on Earth, like muscle
atrophy and the loss of bone mineral density.
CASIS looking to work with
pharma to replicate the
study and perform precision
medicine-type experiments on
identical mice or flat worms
@scripnews
atherosclerosis related to oxidative stress,
inflammation and vascular function.
Another group of researchers from
NASA’s cardio and advanced projects labs
have teamed with UCSD investigators in
conducting a proteomic assessment of
fluid shifts and the association with visual
impairment and intracranial pressure.
Researchers from Northwestern University,
Rush University Medical Center and
the University of Illinois in Chicago are
exploring the astronaut brothers’ dietary
differences and stressors to find out how
both affect the organisms in their guts
through a microbiome experiment involving
metagenomic sequencing.
Researchers at Colorado State University
will be working with NASA investigators
to assess whether spaceflight influences
telomere length and telomerase activity,
with the hopes of providing informative
biological indicators of aging and age-related
degenerative diseases, like cardiovascular
disease and cancer.
Investigators from Johns Hopkins
University are measuring DNA methylation
and chromatin at a genome-wide level
in biological samples obtained from the
Kelly brothers, with the aim of integrating
epigenomic data with exposure to
spaceflight conditions, looking for exposurelinked changes, and by comparison to the
ground-based twin, determining whether
those are transient or long-lived effects.
They also are seeking to determine whether
DNA mutations arise secondarily to those
epigenetic changes.
Researchers at Stanford University are
studying how long-term space travel
affects the immune system, examining
how parameters of the immune system
changes at baseline and after a seasonal flu
vaccination. They are seeking to understand
how the immune response to vaccination
differs in the twins.
Charles noted that because the Russian
Soyuz that brought Kelly back to Earth on
March 2 doesn’t have much extra room, his
blood and urine samples remained up in
space in a freezer on the ISS and are expected
to be brought back on the return flight of the
next SpaceX Dragon mission – a trip in which
Eli Lilly & Co. is sending several experiments
up to the space station next month.
Charles said the Kelly brothers will be
followed for at least the next nine months by
one of the groups of investigators, with most
of the other researchers wrapping up their
studies in the next 60 days to six months.
[email protected]
headline news
Pharma’s Space Frontier: Come On And Take A Free Ride
Mr.Creative/shutterstock.com
Space is waiting for you pharma. So come on
and take a free ride – literally.
Indeed, while NASA astronaut Scott Kelly,
who returned to Earth on March 2, was up in
space on the International Space Station (ISS)
for the past year, with him were hundreds
of biomedical experiments, many of which
were intended to help researchers from
drug companies, the US government and
academic institutions solve the mysteries of
human diseases.
And the American taxpayers footed the bill
– on average of about $7.4m per experiment
– of getting that research from the ground
to space and back, including the costs of
operating the ISS US National Laboratory and
crew time, explained Dr. Michael Roberts,
deputy chief scientist at Center for the
Advancement of Science in Space Inc. (CASIS).
None of that $7.4m – an amount that can
vary – is passed along to the experiment’s
investigators, whether they’re private-sector
firms, universities or non-NASA government
agencies, like the National Institutes of Health,
Roberts told Scrip.
“It’s not part of what they have to come
up with,” said Roberts, whose organization
was selected by NASA in 2011 to manage the
ISS US National Lab, which was created by
Congress in 2005 as a way to open up and
maximize the research opportunities of the
space environment.
Biopharmaceutical companies, academic
institutions or non-NASA government
agencies, however, are responsible for
covering the costs of getting their project
developed and ready for flight and the
supplies needed for the investigation.
But some of those costs may be covered
through CASIS challenge grants or federal
agency funds, Roberts said.
Companies like Merck & Co. Inc., Eli Lilly
& Co. and Novartis AG already have sent
experiments, or soon will, up to the ISS, he said.
Roberts pointed out that microgravity
– whose effects on physiology can mimic
the process of aging and some diseases in
humans on Earth, including muscle atrophy
and the loss of bone mineral density –
provides a unique research environment.
Historically, microgravity research that went
up on the space shuttle was essentially “oneand-done” types of experiments, lasting only
days or weeks, he said.
But now with the ISS, which is orbiting 240
miles above Earth, experiments in space can
last for months, Roberts said.
Merck
Merck’s research on the ISS has focused
primarily on protein crystal growth
experiments of investigational monoclonal
antibodies using microgravity, Roberts said.
“Drug companies utilize the environment
in microgravity to grow these large crystals,
bring them back to Earth, take high resolution
x-ray or neutron diffraction images of
them,” he said. “From that, they can derive
information to better target their drugs so
that they have fewer side effects.”
Drug companies can take their
science and technology into
space and accelerate the pace
of their discoveries
Roberts said CASIS also has had some
discussions with Merck about model organisms
and testing of some of the experimental
therapeutics agents in the company’s pipeline
for potential future missions.
Novartis
Novartis already has flown two drug
research missions to the ISS, which focused
on R&D of products to prevent muscle
loss and combat age-related weakening of
muscles, Roberts said.
“Many societies are aging and there’s a
great interest in looking at ways to maintain
muscle mass and slow the weakening of
bones,” he said.
Novartis’ research was included in the
September 2014 “Rodent Research-1 (RR1)” mission to validate the ISS Rodent
Research Facility, which includes modules for
transporting rodents to and from the space
station and units to handle and house the
rodents, Robert said.
The Rodent Research Hardware System was
designed to allow rodents to spend up to six
months in space, he explained.
“That’s a quarter of their natural life span,”
which is the “equivalent of doing a human study
@scripnews
where you looked at someone for 25-30 years,”
Roberts said, noting that previously, experiments
could be done for only up to 60 days.
The Novartis experiment included five
wildtype mice and five transgenic “knock-out”
mice that lacked the MuRF1 gene, which
is believed to trigger muscle wasting by
degrading muscle protein.
The experiment was aimed at revealing
new molecular targets for treating skeletal
muscle atrophy.
In the follow-up RR-2 mission, Novartis
researchers monitored the effects of the
space environment on the musculoskeletal
and neurological systems, with the idea
of discovering new molecular targets that
can facilitate the development of novel
therapeutics for the treatment of muscle and
bone-related diseases.
The mice in RR-2 also were exposed
to spaceflight for two to eight weeks to
determine the progression of muscle wasting
over time in the mice.
Lilly
Lilly has a very broad-based research approach
with several experiments, including some
focusing on protein crystal growth on drug
formulation, expected to go up to the ISS next
month on the SpaceX CRS-8, Roberts said.
“They’re actually interested in looking at the
physical structure of the drugs they have in
development,” he said.
Roberts said Lilly also has a rodent research
experiment that’s looking at a drug in the firm’s
pipeline intended to prevent muscle loss.
With Lilly’s experiments, 20 mice will be
launched to the ISS, he said.
An Opportunity To Accelerate R&D
For the most part, the experiments from
drug makers involving R&D of medicines
going up to the ISS is for diseases that affect
large populations, like musculoskeletal disease
and metabolic disorders, Roberts said.
He emphasized CASIS does not set the
research agenda.
“We’re simply responding to what the
principal investigators identify as important
areas of research,” Roberts said.
What CASIS does, he said, is aid the US in
ensuring the ISS US National Laboratory, which
provides access to a wide range of hardware
and R&D-enabling technologies, is” most
effectively utilized as a research environment.”
Drug companies and others involved in
biomedical R&D have an opportunity to “take
their science and technology development
up into space and accelerate the pace of their
discoveries,” Roberts declared.
[email protected]
March 18th 2016
15
R&D bites
R&D Bites
All Eyes On Sun’s
Ophthalmology US NDA
Sun Pharmaceutical Industries’
ophthalmology NDA BromSite (0.075%
bromfenac), comes up for US regulatory
approval next month, setting the stage for
a potential push in a segment where the
Indian firm has been prepping for a ramp
up. Bromsite, which has been assigned a
Prescription Drug User Fee Act (PDUFA)
action date of April 10, is the firm’s first
ophthalmology NDA coming up for approval
following the merger of Insite Vision with
Sun. Last year, Sun acquired Insite edging
out previous bidder and Canadian biotech
QLT Inc; the acquisition was completed in
November 2015, with InSite becoming an
indirect wholly owned arm of Sun. InSite is
seeking FDA approval for BromSite in the
treatment of inflammation and prevention
of ocular pain in the post-cataract surgery
setting. BromSite combines a low dose of
bromfenac with InSite’s DuraSite platform,
a synthetic polymer-based formulation
designed to extend the time of a drug in the
eye relative to conventional topical therapies.
BromSite has a patent life extending to
August 2029, Insite said previously. Scrip
affiliate Sagient Research’s BioMedTracker
has placed the likelihood of BromSite’s
approval at 83%, which is 4% above the
average probability of FDA approval for
the specified disease group based on the
historical performance of medicines in the
same development phase, and expects the
PDUFA date to occur on April 8 [April 10 falls
on a Sunday]. Bromsite’s NDA submission
was based upon two Phase III trials that were
conducted in over 500 patients.
Imbruvica Boosts CLL Lead
AbbVie Inc. and Johnson & Johnson’s BTK inhibitor
Imbruvica (ibrutinib) has reinforced its lead
position in the chronic lymphocytic leukemia
market with a first-line indication from FDA. FDA
approval of a supplemental new drug application
(sNDA) for Imbruvica (ibrutinib) for first-line use
in patients with chronic lymphocytic leukemia,
announced March 4, gives the Bruton’s tyrosine
kinase inhibitor from J&J (Janssen Biotech Inc.)
and AbbVie (Pharmacyclics Inc.) the broadest
label of the new generation of targeted therapies
for CLL. Imbruvica is already a blockbuster drug,
topping $1bn in 2015 sales following its 2014
approvals, initially for CLL patients who have
received at least one prior therapy and then for
CLL patients with a 17p genetic deletion. It is a
first-in-class, oral, once-daily therapy that inhibits
the Bruton’s tyrosine kinase protein, a key signalling
molecule in the B-cell receptor signalling complex
that plays an important role in the survival and
16 March 18th 2016
spread of malignant B cells. Imbruvica was one
of the first medicines to receive FDA approval via
the breakthrough therapy designation pathway.
Optimism over the drug’s prospects induced
AbbVie to buy Pharmacyclics, which developed the
medicine with J&J, for $21bn in 2015.
Epizyme Plans: Accelerated
Tazemetostat Approval
A year after losing its big pharma partner,
epigenetic cancer therapy-focused Epizyme
Inc. used its quarterly earnings call on March 9
to outline a four-step strategy for becoming a
commercial company, expanding the potential
uses for lead candidate tazemetostat (EPZ-6438, aka
taz) and bringing at least three novel proprietary
cancer candidates into clinical development by
2020. Central to this strategy is a plan to seek
expedited approval of tazemetostat based on
findings from Phase II studies in various forms
of non-Hodgkin lymphoma (NHL) and in rare
genetically defined solid tumors. CEO Robert
Bazemore outlined a plan by which Epizyme
will seek approval for varying indications based
on data from individual arms of the two Phase II
studies. Bazemore, a lymphoma survivor, joined
the Cambridge, Massachusetts-based biotech
last September after leaving Synageva BioPharma
Corp., where he was the chief operating officer.
The CEO said in an interview prior to Epizyme’s
earnings call that tazemetostat could present
a “platform-within-a-product opportunity.” The
company regained almost all rights to the EZH2
inhibitor last year by paying Eisai Co. Ltd., its
partner since 2011, $40m up front to largely
unravel the collaboration around tazemetostat.
Eisai retains Japanese rights to the compound, and
is responsible for 100% of development costs in
that market.
Celldex Rintega Fails In Phase III
Celldex Therapeutics Inc.’s stock was cut by more
than half to $3.79 per share after the company
revealed that it would discontinue the Phase
III clinical trial known as ACT IV for the cancer
vaccine Rintega (rindopepimut) based on an
interim assessment of survival for glioblastoma
(GBM) patients. Hampton, New Jersey-based
Celldex closed down 53.7% on March 7 following
the disclosure that median overall survival was
20.4 months in the Rintega arm of ACT IV versus
21.1 months in the control group for patients with
newly diagnosed EGFRvIII-positive glioblastoma
and minimal residual disease. The trial’s Data
Safety and Monitoring Board (DSMB) determined
that Celldex’s lead product candidate was unlikely
to meet the study’s primary endpoint based
on the interim survival data. The company said
Rintega’s performance in Phase III was consistent
with past Phase II studies, but the control arm
in ACT IV performed significantly better than
expected. As a result, Celldex “does not anticipate
incurring substantial additional costs related to
Rintega at this time,” the company said, meaning
that it will discontinue development of the cancer
vaccine in all indications.
@scripnews
Imbruvica Leads Sea Change
In CLL Landscape
Johnson & Johnson/AbbVie Inc. ‘s Imbruvica
(ibrutinib) has rapidly established itself as
standard of care in relapsed/refractory chronic
lymphocytic leukaemia and will increasingly
move into the first-line setting following its recent
approval by the FDA for that use in patients with
CLL, analysts say. That accolade was won after
Imbruvica showed good efficacy in first-line CLL
without the need for a chemotherapy backbone.
Whether the BTK inhibitor will maintain that CLL
lead is unclear, as there is a growing number
of new drugs to treat the disease, which is the
most widespread form of adult leukemia. Still, the
innovative dynamism around the condition
looks set to expand the CLL market enormously,
largely because the orally administered drugs will
remove reliance on chemo, and new drug classes
will be administered more frequently than with
previous products.
Bass Wins Review Of Ampyra Patents
Shares of Acorda Therapeutics Inc. tumbled 10.7%
on March 11 after word came late in the day
the Patent Trial and Appeal Board (PTAB) of the
US Patent & Trademark Office agreed to review
four of the firm’s patents on its FDA-approved
multiple sclerosis drug Ampyra (dalfampridine)
in response to so-called inter partes review (IPR)
petitions filed by hedge fund manager Kyle Bass
through his Coalition for Affordable Drugs. The
stock closed the day at $32, down $2.71, or 7.8%.
But Bass failed to win over the PTAB in seeking
a review of a US patent held by Roche AG on
Enbrel (etanercept), a tumor necrosis factor alpha
marketed in the US by Amgen Inc., increasing the
odds the drug will remain patent protected well
into the late 2020s.
Sanofi/Regeneron’s Sarilumab
Stiff Competition
Regeneron/Sanofi’s IL-6 inhibitor sarilumab
has beaten AbbVie’s Humira (adalimumab) in
a head to head trial. Top line Phase III results
show sarilumab more significantly improved
the signs and symptoms of rheumatoid arthritis
after 24 weeks of treatment than blockbusting
Humira did. The data will help differentiate the
drug, but competition will remain fierce in the
RA space, say analysts. “This is the first time an
IL-6 receptor blocker delivered subcutaneously
has demonstrated superiority over adalimumab
monotherapy in RA,” said Janet van Adelsberg,
Regeneron’s senior director of clinical sciences,
immunology and inflammation. Sanofi CEO Olivier
Brandicourt last year said that sarilumab was one
of six key products that would generate combined
peak sales of up to €14bn. The drug is expected
to launch by the end of the year in the US, where
it is undergoing regulatory review. Datamonitor
Healthcare analyst Christina Vasiliou expects
that Sanofi/Regeneron will try and position the
drug early in the rheumatoid arthritis treatment
pathway after patients fail on methotrexate.
However, there will be a lot of competition to beat.
headline news
$1.14bn For Xtandi Royalties: How UCLA Cut Risk,
Diversified Its Assets
With no shortage of offers to buy its royalties
from the prostate cancer drug Xtandi
(enzalutamide), the University of California,
Los Angeles (UCLA) recently decided to
reduce its risk and diversify its holdings by
selling the Xtandi revenue stream, accepting a
bid from Royalty Pharma for $1.14bn.
Privately-held Royalty Pharma kept in touch
with UCLA while Xtandi patent licensee
Medivation Inc. and its partner Astellas
Pharma Inc. developed and commercialized
the drug for later-stage and eventually frontline treatment of metastatic castrate-resistant
prostate cancer (mCRPC). The investment
firm’s tenacity paid off: It beat out four other
bidders in a competitive process to buy the
Xtandi royalties, repeating its history of eyepopping deals with nonprofit research groups.
Royalty Pharma paid $3.3bn in November
2014 to acquire the Cystic Fibrosis Foundation
(CFF) royalty stream from sales of Kalydeco
(ivacaftor), the ground-breaking cystic fibrosis
drug developed by Vertex Pharmaceuticals
Inc. with research funding from CFF.
Executives from the New York-based
royalty acquirer expect to negotiate more
transactions in the future with universities and
patient advocacy groups as those entities get
more creative about financing and benefitting
from their investments in new drugs.
Many Offers, Great Possibilities
UCLA actually owns just 43.875% of the royalty
interest that was sold to Royalty Pharma and
its share of the transaction proceeds is $520m.
The other 56.125% will be shared by the
Howard Hughes Medical Institute along with
the UCLA and Howard Hughes scientists who
discovered Xtandi. The inventors get the bulk
of the remaining proceeds, since the University
of California (UC) system’s patent policy gives
about 35% of royalty proceeds to the inventors
– roughly $400m.
The Royalty Pharma deal was negotiated by
Westwood Technology Transfer, a nonprofit
company that UCLA established in 2014 to
oversee its intellectual property portfolio and
maximize returns from technology invented
by university researchers.
Westwood supports the UC system’s push
to encourage entrepreneurship among
its students and faculty. The UC Board of
Regents approved a $250m venture capital
fund called UC Ventures in 2014 to invest in
companies that spin out of the university
system’s 10 campuses, five medical centers,
three affiliated national laboratories and 20
technology incubators.
18 March 18th 2016
Westwood board member and Los
Angeles-based venture capital investor Tom
Unterman told Scrip that the Xtandi royalty
stream is “a very visible piece of intellectual
property, because it’s so large compared to
what universities and research institutions
typically own. We have been approached
over the years about selling it, but this is not
something the university has done actively
before. We saw the volume of the incoming
calls and thought we should consider it.”
UCLA engaged Goldman Sachs as a financial
advisor to analyze whether the university
should monetize the Xtandi royalty stream,
determine the asset’s value, solicit bids and
broker a transaction; five bids were received
in all. Legal advisors included Gibson Dunn for
UCLA, Goodwin Procter for Royalty Pharma
and Covington & Burling LLP for the inventors.
Heyman Biotech LLC was a strategic advisor
for the inventors, who include UCLA chemistry
and biochemistry professor Michael Jung and
Charles Sawyers, a doctor at Memorial Sloan
Kettering Cancer Center in New York. Sawyers
was an investigator at Howard Hughes while
teaching medicine, urology and pharmacology
at UCLA when the Xtandi-related intellectual
property was created.
Sawyers and his team at Howard Hughes
identified why patients failed to respond to
first-generation prostate cancer therapies and
collaborated with Jung’s lab at UCLA on the
discovery of the second-generation androgen
receptor inhibitor Xtandi. Medivation licensed
the chemical compound’s patent, which
expires in 2027, in 2005. The San Franciscobased biotech company allied with Astellas
in 2009 for global development of Xtandi and
the partners won their first US approval for
the drug in 2012.
Xtandi is approved in the US for both preand post-chemotherapy treatment of men
with mCRPC and recent clinical trials support
the drug’s use early in the treatment of
metastatic patients. Astellas reported $1.9bn
in global Xtandi sales for 2015 and Medivation
collected $695.5m of that revenue in 2015
versus $389.4m in 2014.
UCLA has earned $2.8m in aggregate
milestone fees under its licensing agreement
with Medivation and the university earns
an annual maintenance fee plus 10% of all
sublicensing income from the company’s
agreement with Astellas and a 4% royalty
on global net sales of Xtandi. Astellas and
Medivation share the royalty obligation
equally for US sales, but Astellas pays royalties
to UCLA based on ex-US sales.
@scripnews
Litigation is pending between UCLA
and Medivation to determine whether the
university is getting its fair share. UCLA sued
Medivation in 2014 in a dispute over the
operating profits that the company receives
from Astellas and whether it qualifies as
sublicensing income under Medivation’s
license agreement with the university. The
parties are awaiting a trial court date.
UCLA’s Risk Management,
Diversification Strategy
Unterman said there were two key reasons
why UCLA chose to sell its royalties to
Royalty Pharma: 1) risk management in
the event that a future competitor should
steal significant sales from Xtandi and 2)
diversification of revenue streams that fund
research at the university.
“The drug is on a strong growth trajectory,
but cancer research is moving fast. Strong
competitors could come to the market,”
Unterman said. “If we could get the money
now, we could assure a steady stream of
money for years to come.”
UCLA will hold its $540m share of the
proceeds in a broadly diversified investment
portfolio managed by the UC system’s chief
investment officer. The investment portfolio
is expected to generate $60m in unrestricted
funding [annually] for UCLA through 2027.
Most of the money will fund research, but the
university expects to set aside some cash for
scholarships and fellowships.
So will UCLA via Westwood Technology
Transfer cash in additional pharmaceutical
royalty streams to fund research and
scholarships at the university? It’s possible.
“We do have other therapies that have
been developed at UCLA that we, over time,
would consider doing similar transactions
for, but nothing in the next two or three
years or of this scale,” Unterman said, noting
that most royalty transactions involving
research institutions total $40m to $50m.
He said UCLA scientists sometimes are
approached by investors that want to buy
their and the university’s royalty stream,
but UCLA or the UC system usually are
approached first.
Royalty Pharma vice president of investor
relations and public affairs Alexander von
Perfall said the firm has been interested
in the Xtandi royalties since 2010 when it
began tracking the drug’s clinical trials and
regulatory progress.
Read full story at: http://bit.ly/1YVWpjL
[email protected]
headline news
Using Patient Biology To Shepherd
Clinical Trials
“Pharma is throwing the term precision
medicine around but it still doesn’t really
understand what it will take to achieve
it,” according to the world’s first chief
precision medicine officer, BERG Health’s
Michael Kiebish. BERG is combining artificial
intelligence and systems biology to analyze
stacks of biological data.
According to Kiebish, there needs to be
a lot more collaboration: governments and
pharmaceutical companies need to open
up their data repositories, there needs to be
better infrastructure to cope with the volume
of electronic data becoming available, and we
need to develop better analytical tools, “and
not just genomics [tools], but adaptive ‘omics’
like metabolomics, proteomics, lipidomics.”
The data repositories and analytics need to be
built up and then we have to allow people to
“dig into that data.”
BERG was initially founded to develop
an oncology asset, but quickly realized that
“the use of artificial intelligence, population
diversity and ‘omics’ could be used to develop
biologics for lots of diseases.”
“There were lots of pieces missing in the
drug development cycle. First and foremost,
the patient,” he told Scrip.
Platform
All of BERG’s research and clinical trials
employ its Interrogative Biology platform.
This “back to biology approach” is completely
different from the traditional pharma
approach to drug discovery through
chemical libraries and hypotheses.
BERG collects patient samples in both
diseased and healthy states which are
processed by high throughput mass
spectrometer workflow. Biological activity is
analyzed through adaptive ‘omics’. “We also
look at mitochondrial function, oxidative
states and ATP production to examine how
the cells are functioning.”
The process produces trillions of data
points from a single sample. The data is then
combined with patient clinical information
and analyzed by BERG’s artificial intelligence
machine learning analytics program. This
combination of systems biology and artificial
intelligence constitutes the Interrogative
Biology platform.
BERG builds its drugs in molecules and
targets based on population diversity to “get
into the core biological causes of disease,”
says Kiebish. “Patients are a part of the drug
discovery process from the beginning. Patient
biology is shepherding the clinical trial
process.” And that is the definition of precision
medicine, he claims.
However, before that can truly become a
reality, there has to be education. Governments
and pharma must make a “social contract” with
patients “so there is understanding that it will
take time, it is still your data, and it will be used
for the greater good.”
Kiebish joined BERG in 2012 as vice
president of systems medicine before being
appointed to his new role.
Objectives
“My near term objectives are to try and evolve
the bioanalytics and informatics platforms to
be quicker, more economical, to engage more
in the clinical trial process.
“In the mid term, I want to be establishing
collaborations with the big analytical/
informatics hardware companies, and hospital
insurance companies.
“In the long term I will be keeping my
eye on the prize. Developing those proof
points for oncology, not just for our drug, but
through companion diagnostics for other
drugs. We want to help develop new pharma
economic models to overcome outcome
based reimbursement, the patent cliff.”
BERG was founded by Silicon Valley billionaire
Carl Berg, so doesn’t follow the model of a
traditional venture capital backed biotech. “We
want to evolve into a lean, adaptive, healthcare
solutions company where we build diagnostics
globally, nurture our pipeline, understand the
whole landscape of combination therapies for
different diseases based on real time biology,
and collaborate heavily with big pharma and
IT companies. We want to position patients to
have real time access to their health, through
connectivity via wearable devices, empowering
patient knowledge.”
Kiebish says BERG has “lots of kettles
boiling” regarding collaboration discussions
but pharma “likes to see companies prove
themselves in stages” and hence BERG is
focusing on its pipeline.
Pipeline
BERG has two therapeutic products in earlystage clinical testing.
BPM31510 is in Phase I/II trials as a
monotherapy for squamous cell carcinoma
and as a monotherapy and a combination
therapy for advanced refractory solid tumors.
BPM31543 is in Phase I trials as a topical
treatment for chemotherapy-related alopecia.
“2016 will be an interesting year for our
pipeline,” says Kiebish. [email protected]
@scripnews
Has FDA Lost
Its Grip? The
Amarin Deal
While the FDA was insistent its settlement
with Amarin Corp. plc, which a federal
district judge has signed off on, only
applies to that company, in which the
agency has agreed to not stand in the
way of the firm sharing “truthful and nonmisleading” information about certain
unapproved uses of its fish-oil pill Vascepa
(icosapent ethyl), the deal, nonetheless,
shows US regulators can be flexible, or at
least, when they’re backed into a corner.
Indeed, to the FDA, the deal with
Amarin likely was the choice of the lesser
of two evils – settle the legal dispute and
let the company have its way, although
with input from the agency, or wind up in
an appeal, which had the chance of going
badly for regulators, resulting in them
losing their grip completely over off-label
promotional activities.
It was clear the FDA didn’t want to
risk the possibility of the latter situation
happening when it agreed this past August
to explore a potential settlement with
Amarin, which a few weeks earlier had
been granted a preliminary injunction by
Judge Paul Engelmayer of the U.S. District
Court for the Southern District of New York,
who said the company could share certain
“truthful and non-misleading” information
about Vascepa “without incurring liability
for misbranding” – a verdict that was a
major blow to the US regulatory agency.
The FDA already had walked away from
appealing its loss in an earlier decision,
in which the US Court of Appeals for
the Second Circuit in Manhattan had
overturned the October 2008 conviction
of a New York sales representative, Alfred
Caronia, for conspiracy to introduce
a misbranded drug into interstate
commerce related to discussions he had
with doctors about unapproved uses for
Jazz Pharmaceuticals Inc.’s narcolepsy
drug Xyrem (sodium oxybate).
In that case, the Second Circuit ruled
that “truthful” off-label promotion of US
approved prescription drugs is not criminal
activity and is protected speech under the
First Amendment of the US Constitution.
The FDA this past December also
reached an agreement in another
free-speech lawsuit with Pacira
Pharmaceuticals Inc.
Read full story at: http://bit.ly/1WekIHY
[email protected]
March 18th 2016
19
business bulletin/policy & regulation briefs
Business Bulletin
Patient Groups Rank
ViiV Top Of Pharma
League Table
The latest PatientView report on the corporate
reputation of pharma from the perspective
of patient groups has been published. In a
survey of pharma’s corporate reputation, ViiV
Healthcare retained the overall top spot, with
AbbVie a close second. Of the 48 companies
that patient groups commented on, the
bottom ranked companies were Valeant and
Hospira. 2015 was a watershed year for pharma’s
investment in relationships with patient groups
and other patient-centric activities. This was
reflected in pharma’s best standing in terms
of corporate reputation since the survey was
first conducted in 2011. The survey questioned
1,075 patient groups from 72 countries on six
indicators of corporate reputation: patientcentricity; patient information; patient safety;
useful products; transparency; integrity. The
report also questioned 11 pharma companies
on their activities in patient centricity and
patient-group relations.
Aprea Banks $51m Series B
Aprea AB, which is targeting the “holy grail” of
anticancer research – the p53 tumor suppressor
protein – and has the former head of oncology drug
discovery of Bristol-Myers Squibb as its executive
chair, has raised SEK 437m ($51m) in a series B
financing. The transaction sees former majority
shareholder Karolinska Development drop its stake
from 62% to around 19% via the conversion of SEK
60m of outstanding loans. The deal marks a year since
Karolinska Development’s CEO Jim Van heusden took
over the top job and was given the task of changing
its strategy in a bid to change its fortunes. He has
been busy spinning out portfolio companies such
as Pharmanest and XSpray Microparticles to sharpen
Karolinska’s focus, and also attract outside investment
into the companies it retains.
Spark Acquires Irish
Ophthalmology Partner
Philadelphia-based Spark Therapeutics has acquired
private, Irish gene therapy company, Genable
Technologies, for $6m in cash and 265,000 shares
of Spark common stock. Spark and Genable have
been partners since 2014 on the development
of RhoNova, a drug targeting rhodopsin-linked
autosomal dominant retinitis pigmentosa (RHOadRP), a form of inherited retinal disease (IRD).
Through the acquisition Spark will gain full
ownership of RhoNova, which is currently being
explored in preclinical studies for RHO-adRP, a
condition that leads to visual impairment and
in the most severe cases to blindness. Using an
adeno-associated virus (AAV) vector developed and
manufactured at Spark, RhoNova, which has been
granted orphan drug designations in the US and
Europe, is designed to both suppress the expression
of a faulty gene and deliver normal copies of the
RHO gene to restore normal expression.
Policy & Regulation Briefs
Indian Court Rejects
Whistle-Blower’s Suit
India’s apex court has declined to admit
Ranbaxy whistle-blower Dinesh Thakur’s
petitions that sought “urgent intervention”
to improve India’s drug regulatory standards
and challenged the constitutionality of
certain rules under the Drugs and Cosmetics
Rules 1945. Thakur had moved the Supreme
Court against India’s health ministry, the
Central Drugs Standard Control Organization
(CDSCO) and the Drugs Consultative
Committee, among others, seeking a series
of actions to improve the drug regulatory
system in India, including “binding
guidelines” for the recall of drugs that are
not of standard quality, adulterated, spurious
or misbranded. On March 11, the Supreme
Court took up Thakur’s much publicized
plea, but is said to have questioned the
whistle-blower’s locus standi and apparently
indicated that it had no time for publicity
efforts by public activists.
20 March 18th 2016
No 12 Years Exclusivity In Biologics
NDA-To-BLA Switch
Even though the Biologics Price Competition and
Innovation Act (BPCIA) – the law that permitted
the FDA to approve biosimilars – has been in place
since March 2010, it’s taken the agency six years
to figure out how to implement the so-called
“deemed to be a license” provision, which sets a
deadline for regulators to stop approving biologics
through certain pathways created under the Food,
Drug and Cosmetic Act (FDCA). In a new draft
guidance document posted online on March 11,
the FDA laid out a new plan for moving protein
products, like insulin and insulin analogues,
human growth hormone, pancreatic enzymes
and follitropin, which have been approved for the
US market through the FDCA pathways – new
drug applications (NDAs), abbreviated new drug
applications (ANDAs) or 505(b)(2) NDAs – to the
biologics license application (BLA) process.
Round 2 ‘Innovation’ Bills Adopted
A second set of bills intended to overhaul the US
biomedical enterprise, aimed at accelerating the
discovery, development and approval processes
for medical products, mostly had smooth sailing
through the Senate Health, Education, Labor and
@scripnews
TiGenix Raises $26m, Fistula Therapy
Continues To Fizz
The European leader in investigational allogeneic
stem cell therapies, Belgium’s TiGenix NV, has
turned its back for now on raising funds on
Nasdaq, and has instead raised gross proceeds
of €23.75m ($26.2m) in a private placement on
Euronext Brussels completed Mar. 10, just days after
it described the benefits of its lead product Cx601
at 52 weeks after administration, a longer period
than previously reported. TiGenix has been publicly
listed on Euronext Brussels since 2007 and was
planning to raise funding in the US, but reported
Mar. 9 that unfavorable capital market conditions
meant it had not yet launched an initial public
offering of American Depository Shares (ADSs).
Xoma Kills Gevokizumab
Xoma Inc. finally stopped all development for
gevokizumab, shifting its entire focus to endocrine
diseases and cutting even more jobs, but the
company somehow expects to sell the asset to
another party after racking up another Phase
III clinical trial failure. Berkeley, California-based
Xoma’s share price flirted with the $1 range on
March 10 as investors responded to the company’s
2015 earnings report and corporate update,
which was issued after the stock market closed on
March 9. But Xoma ultimately ended the day just
shy of $1 per share – up 8.1% at $0.96 – after the
company hammered the final nail in gevokizumab’s
coffin and said it would use its remaining cash to
advance three development programs in various
rare endocrine diseases.
Pensions (HELP) Committee on March 9, with only
a somewhat brief debate over how the measures
will be funded holding up the votes for a short
time. The seven bills, which were a hodge-podge
of measures that would add new responsibilities to
the FDA and the National Institutes of Health (NIH),
are intended to eventually be wrapped up into a
package that would serve as a companion to the
House-passed 21st Century Cures Act.
Valeant ‘Puzzled’ Over Accusations
Valeant Pharmaceuticals International Inc. on
March 10 said it was “surprised and puzzled” by the
accusations from the Republican and Democratic
heads of the House Oversight and Government
Reform Committee that the firm was withholding
documents. “We have produced more than 78,000
pages of documents,” said Washington lawyer
Robert Kelner, a partner at Covington & Burling,
who is representing Valeant. Kelner said it was
“standard procedure” for any company responding
to a congressional investigation and engaged
in litigation to decline to produce documents
covered by the “attorney-client privilege,” and said
his firm was preparing a log for the Oversight
Committee detailing what documents were being
withheld under that privilege.
expert view
Can Premium-Priced Trulicity Prickle Victoza In India?
Eli Lilly’s once-weekly diabetes therapy
Trulicity (dulaglutide) appears to have made its
Indian debut priced at a premium compared
with certain Western markets –an indication
that some innovator firms are less likely to
consider major pricing flexibilities in first-wave
markets for new products, even if these are
emerging economies.
India is among the first few countries in the
world and the third Asian market after the
UAE and Japan where Trulicity has been rolled
out and the glucagon-like peptide-1 (GLP-1)
receptor agonist has been priced at INR2,499
(£26) for a week, translating into an annual
cost of around INR129,948 (£1354.5).
In contrast, the annual cost in the UK
of dulaglutide 1.5mg or 0.75mg once
weekly is £1,182.35, as per details in NICE’s
evidence summary for the product in June
2015, though an out-of-pocket market like
India may not be strictly comparable with
reimbursed markets like the UK. The exact
impact of currency fluctuations on pricing
was not immediately clear.
Asked about the pricing approach in India
and the premium compared with markets
like the UK, Lilly said that it believes Trulicity’s
price reflects both the “current market and
competitive realities” while still allowing this
important class to grow as it continues to
serve more patients.
“Every market is different in regards to
pricing, access and reimbursement. Lilly
offers Trulicity at a price which we believe is
reflective of what the product offers, including
proven efficacy, safety and patient-friendly
administration,” Lilly told Scrip.
One industry expert told Scrip that Lilly’s
price point was a reflection of how the first
wave of markets launch at “approximately the
US price,” while tiered-pricing or other such
flexibilities come in slightly later.
“India is among the first wave markets to
launch which is an acknowledgement by
Lilly of India being the diabetes capital of the
world. It’s a market that they would launch
earlier rather than later,” the expert with a
foreign firm said.
India has more than 60m people living
with diabetes, while 77.2m Indians are seen as
pre-diabetic (impaired fasting glucose and/or
impaired glucose tolerance).
The expert, though, said that India
continues to be a volume driven market and
in the absence of insurance cover and patients
paying out of pocket, Lilly will probably not
see “really big volumes” unless it drops price.
“However, given the nature of the product
(once weekly), Lilly’s strategy could be a ‘value
capture’ one too since it may target a smaller
patient population than its other traditional
insulins,” the expert told Scrip.
Foreign firms have deployed a number of
pricing approaches in India: Novo Nordisk’s
once-daily basal insulin therapy Tresiba
(insulin degludec) had some years ago made
a similar premium debut, positioning itself
at the top end of the private market. It had a
strong run with an estimated 6,000 patients
prescribed Tresiba in India within just two
months of launch.
In contrast Janssen launched its selective
sodium glucose co-transporter 2 (SGLT2)
inhibitor Invokana (canagliflozin) for type 2
diabetes in India at a fraction of the product’s
US cost sticking with its “commitment” of
offering India-specific pricing for its products as
far as possible. Ditto for AstraZeneca’s Forxiga
(dapaglifozin) that was priced 75% lower in
India as compared with developed markets.
Competition
Some experts appear to give Trulicity a fair
chance of making a dent in India, premium
price approach notwithstanding.
Ripple Mehta, senior consultant at MP
Advisors, an Indian strategic business advisory
firm, told Scrip that Trulicity will be a drug of
choice for patients uncontrolled with two or
three oral antidiabetics and are obese and
need to start insulin.
“The high price makes it a treatment of
choice for rich, obese diabetics,” Mehta said,
adding that she expects the product to take
market share from Novo Nordisk’s Victoza
(liraglutide), which is administered once daily.
Victoza continues to be very successful, but
has lost some market share to other GLP-1
agonists, including Trulicity, internationally.
Novo Nordisk’s Victoza is available as a 6mg
per ml solution for injection in a pre-filled pen.
One pre-filled pen contains 18mg liraglutide
in 3ml that costs INR4,840.
Novo Nordisk, however, told Scrip that
based on its interactions with prescribers,
most of the patients in India are prescribed
0.6mg–1.2mg.
“The weekly cost of Victoza is lesser than
the newly launched molecule dulaglutide
for most patients in India. For a 0.6mg dose,
Victoza is economical by around INR1,370 per
week (vis-à-vis dulaglutide) and for the 1.2mg
dose, Victoza is economical by INR240 per
week,” Novo Nordisk told Scrip.
For all patients the starting dose is 0.6mg
liraglutide daily; patients are expected to
benefit by increasing the dose to 1.2mg
and further to 1.8mg based on the clinical
response, though a daily dose higher than
1.8mg is not recommended.
@scripnews
Mehta believes that Trulicity may also
be able to wean away some market from
SGLT2 inhibitors like Forxiga and Jardiance
(empagliflozin) largely on account of the
latter’s side effect profile.
“Long term use of SGLT2 inhibitors needs
close monitoring. Trulicity may fetch some
market from this class of drugs due to its once
weekly convenience of use, with weight loss/
highHbA1c reduction benefit despite being
an injectable. “
Mehta also added that Victoza’s positive
cardiovascular outcomes data from the
LEADER trial announced recently, increases
the possibility of broader uptake of the
GLP-1 class in the early armamentarium
of treating Type 2 diabetes replacing new
oral combo medications. On March 4, Novo
Nordisk announced top-line results from
the LEADER trial, indicating that Victoza
significantly reduces the risk of major adverse
cardiovascular events.
Trulicity received US FDA approval
in September 2014 and EU approval in
November that year. It comes in an easy
to use, single-dose pen that does not
require mixing or measuring and can
be administered at any time of the day,
independent of meals.
Lilly India’s medical director, Tarun Puri,
said that GLP-1 agonist class provides several
benefits including a proven efficacy in
controlling blood sugar levels with a lower risk
of hypoglycemia. “It might even help patients
reduce a little weight,” a company statement
quoting Puri said.
The Indian diabetes market is valued at
around INR78.17bn ($1.16bn) and growing
at 22.7%, as per moving annual total (MAT)
data for January 2016 from AIOCD AWACS, a
market research agency that tracks retail sales.
While Lilly did not immediately provide
details on Indian studies for Trulicity, at
the time of recommending the product
for marketing authorization in late 2014,
an Indian Subject Expert Committee (SEC)
suggested that Lilly conduct a “structured”
PMS [post marketing surveillance] study.
“The study protocol of the same is to be
submitted to DCGI [Drugs Controller General
of India] office before marketing the drug
in the country,” the SEC (metabolism and
endocrinology) then said.
SECs advise the Indian regulator on trialrelated permissions as part of a layered
approval process, India currently follows
a three-tier review process for clinical
trials, under which applications are initially
evaluated by specialized SECs.
[email protected]
March 18th 2016
21
stockwatch
Pharmaceutical Fight Club
Viktor Gladkov/shutterstock.com
Last week was a hard week for life science
stocks comprising three down days in the
middle of the week that made me wonder
about early retirement followed by a strong
enough recovery on Friday to entice me
back into the office on Monday. Even if we
are close to a bottom if not a recovery in
biotechnology and pharmaceutical share
prices, it doesn’t help the sector ambiance
that everyone seemed to be fighting each
other last week.
We are in the long tail of fourth-quarter
earnings season and by now most of the
reports are by loss-making companies.
Amongst them are all three of those that
developed the most recently approved
medicines to treat obesity. Orexigen
Therapeutics Inc. reported a paltry $2.6m
in quarterly royalties from its partner
Takeda Pharmaceutical Company Limited
in respect of sales of Contrave (naltrexone/
bupropion), now in its second year on the
market. Competitor Arena Pharmaceuticals
Inc. reported only $3.9m in quarterly royalties
from its partner Astellas Pharma Inc. in respect
of sales of Belviq (lorcaserin), which, as the
analysts from JP Morgan and Piper Jaffray
both highlighted, lost 16% in market share
last quarter.
The analysts from JP Morgan (under) stated
that “overall obesity [was] not meeting growth
expectations” while those from Piper Jaffray
cut their share price target on Orexigen,
noting that their estimates on its profitability
were based on growing revenues. By the time
that Vivus Inc. reported $14m in quarterly net
sales for Qsymia (phentermine/topiramate),
a sales figure – like that of Belviq’s – that
had declined in the last quarter, I wondered
if I had been the first to realize that the
three companies actively competing with
recently launched medicines in the obesity
indication appeared to be not so much
in a confrontation, but a hapless series of
misadventures.
22 March 18th 2016
There were, however, confrontations
more worth the effort last week with bigger
opponents Amgen Inc. facing off in court to
challenge the intellectual property of partners
Sanofi and Regeneron Pharmaceuticals Inc. on
PCSK9 inhibition in the treatment of elevated
lipids. Whatever the outcome, at least the
lawyers will win – and if Amgen does prevail,
the confrontation is likely to be settled by
royalties at dawn. Ironically, like the three
recently approved drugs to treat obesity,
the great white hopes for PCSK9 inhibition
are the ongoing cardiovascular outcome
trials (CVOT). Expectations are perhaps
too high for a dramatic turnaround in the
commercial fortunes of any of these drugs,
since – as Novartis AG has found – even in
the face of a positive CVOT the commercial
confrontation appears to be with pharmacy
benefit managers, which are adverse to
paying up for expensive drugs indicated for
large populations, regardless of the clinical
outcomes in those populations.
In Europe last week another confrontation
inched closer to a partial resolution with the
revocation of one of Biogen Inc.’s patents
on the 480mg dose of Tecfidera (dimethyl
fumarate) for the treatment of multiple
sclerosis. The patent challenge had been
initiated by Forward Pharma A/S, whose sole
reason for being seems to be to challenge
Biogen’s patents, although I had wondered
if dimethyl fumarate’s long history of use in
inflammatory diseases in Europe may result in
Forward opening Pandora’s box, inside which
no party ends up with European exclusivity.
Nevertheless, all the analyst notes I read
suggested absolutely no read-through from
Europe to Biogen’s US patents on Tecfidera,
which was a stunning piece of analytical
insight bearing in mind the reasons for the
revocation have not yet been published.
Another patent confrontation in another
court also commenced last week between
Gilead Sciences Inc. and Merck & Co. This
@scripnews
one has much higher stakes. The patents
surrounding Gilead’s multi-billion dollar HCV
antiviral franchise were being challenged
by Merck. Like the PCSK9 challenge, while
the eventual outcome may be solved by
royalties – which the analysts from Jefferies
estimate to be worth $2.3bn to date – the
real confrontation will also be between any
company with a successful HCV antiviral and
those who are contracted to pay for it.
Developing drugs for which there is no
commercial market, or downplaying the
fragility of their intellectual property, may
cause confrontation between companies,
but they often arise from the inability of
companies to confront their own issues of
drug development and convey them to their
investors. In this respect, there is probably
a confrontation brewing with Circassia Plc’s
imminent Phase III trial announcement for its
lead Cat-SPIRE allergy vaccine. Circassia has a
track record of opacity in its clinical trial failure
reporting – I am recalling the time when the
same platform that generated the Cat-SPIRE
vaccine failed to show a significant difference
over placebo for the Phase II Ragweed-SPIRE
allergy vaccine in the low bar of an exposure
chamber clinical study.
Circassia may hope to divert investors’
attention if Cat-SPIRE fails in the real-world
Phase III clinical study by emphasizing the
£10.2m in last-quarter sales it reported
last week. These sales were generated by
spending £188m of the £191m raised in its
IPO and £275m secondary offering to buy
two companies. While some of last week’s
confrontations will be resolved by careful
mediations, others are likely to lead to tears at
bedtime rather than royalties at dawn.
The Magna Biopharma Income fund
holdings include Amgen, Regeneron, Gilead
and Merck.
Andy Smith
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.
For all Stockwatch articles visit
scripintelligence.com/stockwatch
pipeline watch
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.
Late-stage clinical developments for the week 4-10 March 2016
Lead Company
Partner Company
REGULATORY APPROVAL
CSL Behring
–
Vertex
Pharmaceuticals
Inc.
Eisai Co. Ltd.
–
Neopharm
SUPPLEMENTAL REGULATORY APPROVAL
AbbVie Inc.
Johnson & Johnson
REGULATORY FILING ACCEPTED
Vericel Corp.
–
Drug
Indication
Market
Comments
Idelvion
(albutrepenonacog alfa)
hemophilia B
US
Orkambi 200/125
(lumacaftor 200mg and
ivacaftor 125mg)
Lenvima (lenvatinib)
cystic fibrosis
Australia
For use in children and adults with hemophilia B. It is the first coagulation factoralbumin fusion protein product to be approved, and the second Factor IX fusion
protein product approved in the US that is modified to last longer in the blood.
For the treatment of cystic fibrosis in patients age 12 years and older who are
homozygous for the F508del mutation in the CFTR gene.
thyroid cancer
Israel
Indicated for the treatment of adult patients with progressive locally advanced or
metastatic, differentiated (papillary, follicular, Hürthle cell) thyroid carcinoma
refractory to radioactive iodine.
Imbruvica (ibrutinib)
chronic lymphocytic
leukemia
US
Approved as a first-line treatment for patients with chronic lymphocytic leukemia
(CLL). IMBRUVICA is now approved to treat CLL patients regardless of their
treatment history (treatment-naïve and previously-treated patients).
MACI (matrix applied
characterized autologous
cultured chondrocytes)
knee cartilage defects
US
A BLA has been submitted for MACI, an autologous cellular product to treat
symptomatic cartilage defects of the knee in adult patients.
pediatric psoriasis
US
FDA has accepted a sBLA for expanded use of Enbrel in pediatric patients with
chronic severe plaque psoriasis. The sBLA, submitted on Jan. 5, 2016, is based on
results from a Phase III one-year study and its five-year open-label extension
study in pediatric patients with moderate to severe plaque psoriasis.
FDA has accepted for review a new sBLA to include data from KEYNOTE-010, a pivotal
Phase II/III study comparing Keytruda to chemotherapy on the prospective
measurement of PD-L1 expression in previously treated patients with advanced NSCLC.
SUPPLEMENTAL REGULATORY FILING ACCEPTED
Amgen Inc.
–
Enbrel (etanercept)
Merck & Co Inc.
–
Keytruda (pembrolizumab)
non-small cell lung cancer US
(NSCLC)
ORPHAN DRUG DESIGNATION
AstraZeneca PLC
–
MEDI-551
neuromyelitis optica
US
For the treatment of neuromyelitis optica (NMO) and neuromyelitis optica
spectrum disorders. Currently in Phase IIb for NMO.
FAST-TRACK STATUS
AstraZeneca PLC
–
MEDI-8852
influenza A
US
For the treatment of patients hospitalised with Type A strain influenza. MEDI8852 is in a Phase Ib/IIa clinical trial as a single iv dose in combination with
oseltamivir, and as a monotherapy, in adult patients.
Nuedexta
(dextromethorphan /
quinidine)
pseudobulbar affect
EU
The European Commission withdrew the marketing authorisation for Nuedexta in
the EU at the request of Jenson Pharmaceutical Services, which notified the
European Commission of its decision not to market the product in the EU for
commercial reasons.
Xilonix (MABp1)
elvitegravir, cobicistat,
emtricitabine and tenofovir
(E/C/F/TAF)
colorectal cancer
HIV
EU
Japan
For use of an anti-IL-1a MAb for the treatment of advanced colorectal cancer.
An anti-HIV single tablet regimen. Torii holds exclusive rights to market E/C/F/TAF
in Japan, subsequent to JT obtaining manufacturing and marketing approval.
SUPPLEMENTAL REGULATORY FILING
Novartis AG
Genmab
Arzerra (ofatumumab)
chronic lymphocytic
leukemia
EU
For use with fludarabine and cyclophosphamide (FC) to treat relapsed chronic
lymphocytic leukemia (CLL). The application was submitted by Novartis under its
ofatumumab collaboration with Genmab.
PARTIAL HOLD LIFTED
Medivation Inc.
CureTech
pidilizumab
diffuse large B-cell
lymphoma
US
FDA has lifted the partial clinical hold in hematological malignancies and
confirmed the Phase II clinical trial in relapsed or refractory diffuse large B-cell
lymphoma, as well as other studies that cross reference the IND, may now
proceed. The partial clinical hold was not related to any safety concerns.
ofatumumab
subcutaneous
relapsing multiple
sclerosis
–
ARX-04 (sufentanil)
sublingual tablets
OMS721
ThermoDox (heat activated
liposomal doxorubicin)
moderate to severe pain
following surgery
aHUS
hepatocellular carcinoma
–
Novartis to begin Phase III studies with subcutaneous ofatumumab in patients
with relapsing multiple sclerosis during the second half of 2016, following the
transfer of rights to ofatumumab in this disease area from GSK to Novartis at the
end of 2015. The Phase III study of the subcutaneous ofatumumab in pemphigus
vulgaris, which was started by GSK will be discontinued to focus on relapsing
multiple sclerosis.
Patient enrollment and dosing in a multicenter, open-label Phase III clinical
study, known as SAP303, has been initiated.
A Phase III study in atypical hemolytic uremic syndrome has started in the US.
The Phase III study, OPTIMA, has started to enroll patients in China with
hepatocellular carcinoma, as well as in other countries.
REGULATORY FILING WITHDRAWAL
Otsuka Holdings
–
Co., Ltd.
REGULATORY FILING
Xbiotech Inc.
–
Japan Tobacco Inc. Torii Pharmaceutical Co.
Ltd.; Gilead Sciences Inc.
PHASE III TRIAL INITIATION
Novartis AG
Genmab
AcelRx
Pharmaceuticals
Omeros Corp.
Celsion
–
–
–
US
China
Source: Sagient Research's BioMedTracker
@scripnews
March 18th 2016
23
appointments
Ameet Nathwani has been appointed to Sanofi’s
executive committee – effective May 1, 2016.
Nathwani joins the company from Novartis’ taking
the position of executive vice president, group
chief medical officer. From 1994 he held senior
leadership roles in research and development in
Glaxo, SmithKline Beecham and GlaxoSmithKline
PLC. He joined Novartis in 2004 as senior vice
president and global development head of the
cardiovascular and metabolic franchise and held
various senior development and commercial
positions over the 11 years he was there. He was
appointed global head of medical affairs Novartis
Pharma AG. in June 2014.
Specialist investment manager Pamplona
Capital Management has appointed Mark
Pacala operating partner with a focus on
healthcare. Pacala brings over 20 years’
healthcare industry experience and most
recently was a senior advisor in the healthcare
team at Oak Hill Capital Partners. He was also
general partner at Essex Woodlands Health
Ventures and chair and CEO of American
WholeHealth and Forum Group.
Alzheon Inc. has appointed clinical professor
Dennis H. Langer to its board of directors.
Langer is currently clinical professor in the
department of psychiatry at Georgetown
University School of Medicine and director of
Myriad Genetics Inc., Dicerna Pharmaceuticals
Inc. and Delcath Systems Inc. He previously held
executive-level positions at GlaxoSmithKline PLC.
and its predecessor, SmithKline Beecham, most
recently as senior vice president of research and
development.
CRISPR Therapeutics has appointed Marc Becker
chief financial officer (CFO); he joins the company
from rEVO Biologics where he was CFO and senior
vice president. Prior to this, he spent 10 years at
Genzyme, most recently serving as finance director
for the UK and Ireland before becoming the vice
president of finance for the Genzyme’s renal and
endocrine business in the US.
Synergy Pharmaceuticals Inc. has appointed
Marino Garcia to the newly created role of
executive vice president and chief strategy officer
– effective immediately. Garcia has been senior vice
president corporate development and part of the
leadership team since he joined Synergy in 2014.
Previously he was vice president of global business
development at Aptalis Pharma (acquired by
Forest Labs) and vice president of US commercial
operations and new product development at
Aspreva Pharmaceuticals (acquired by Vifor
Pharmaceuticals). Earlier in his career, Garcia held
various US and international leadership roles in
companies like Eli Lilly & Co and Pfizer.
Immunology focused biotech, Mologen AG.’s
supervisory board has appointed Walter Miller
member of the executive board and chief financial
officer (CFO) – effective April 1, 2016. Miller has
experience in working at startups and listed
companies in Germany and abroad and most
recently was CFO of Nuvisan GmbH. Prior to this
he held various managerial positions at Santhera
Pharmaceuticals Group.
PuretTech’s Vedanta Biosciences has appointed
Genzyme’s former vice president Bruce L. Roberts
as chief scientific officer. Roberts most recently was
head of neuro-immunology and immune-mediated
disease research at Sanofi Genzyme.
NantKwest, an immunotherapy company
focused on the immune system, has appointed
Fatih M. Uckun vice president of research and
clinical development. Prior to joining NantKwest,
Uckun was president of Ares Pharmaceuticals
and he was also a professor in the department
of pediatrics at the Keck School of Medicine of
the University of Southern California and head
of translational research in leukemia and
lymphoma of the Children’s Center for Cancer
and Blood Diseases.
Diabetes focused Poxel has named Jonae R.
Barnes senior vice president, investor relations
and public relations. Barnes started her career at
Sepracor (now Sunovion Pharmaceuticals) where
she held various management and executive
roles over a 14 year period and most recently was
senior vice president, investor relations, corporate
communications and internal communications.
She also held senior leadership roles at Agenus.
Let’s get
Social
We are tweeting, chatting, liking and
sharing the latest industry news and
insights from our global team of editors
and analysts, join us!
@scripnews
24 March 18th 2016
@scripnews
/scripintelligence

3794 - Scrip

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