Beyond Borders: Global biotechnology report 2010

orphan drugs were challenging for larger
organizations, which were focused on
high-volume blockbusters. Now, with the
end of the blockbuster era, the economics
are changing and moving the focus to small
patient populations and therapeutics that
focus on severe, unmet medical conditions
where a differentiated patient outcome can
be demonstrated. As a result, orphan drugs
are getting some serious consideration
from big pharma. For instance, Gaucher’s
Disease, a genetic condition in which a
fatty substance accumulates in cells and
certain organs, currently affects 1 in
50,000–100,000 people. Pfizer entered
an agreement with Israel-based Protalix
in December 2009 for the development
and commercialization of its product
taliglucerase alfa. Taliglucerase alfa is
the first enzyme replacement therapy
derived from a proprietary plant cell-based
expression platform using genetically
engineered carrot cells.
Also for Gaucher’s, in September 2009,
the FDA gave Shire’s product VPRIV a
fast-track approval designation. Prior to
its eventual approval in February 2010,
VPRIV was being prescribed to Gaucher’s
patients on an emergency basis for several
months due to the shortage of Genzyme’s
Cerezyme, a result of manufacturing
problems in the middle of 2009.
Adapting to REMS
In response to growing concerns about
product safety, The Food and Drug
Administration Amendments Act of 2007
created the Risk Evaluation Mitigation
Strategy (REMS) program to manage drug
safety risks after products have been
brought to market. The FDA can require
REMS from manufacturers when it finds
they are necessary to ensure that products’
benefits outweigh their risks. A REMS
typically includes a medication guide as well
as a communication plan to discuss side
effects and potential adverse effects of the
approved product with physicians.
In 2009, the FDA continued to rely on the
REMS program as a core component of
its approach to approving products. As of
March 2010, the FDA has approved a total
of 107 REMS, up from 21 that had been
approved as of December 2008. Eleven of
the 29 (38%) NME and BLA drug approvals
had REMS in 2009, which is relatively
consistent with 2008, when one-third of
products were approved with REMS. In
the long run, many hope REMS can help
reduce approval times and get new drugs to
patients faster.
Drug manufacturers have had to adapt
by preparing for the possibility of a REMS
requirement prior to applying for an NDA,
since a launch could get postponed if a
company is not prepared to comply. As
the program proceeds, most companies
will acquire experience producing a REMS,
and it will naturally become a part of the
application process checklist.
In some instances, the REMS program has
provided a “second life” for drug approvals,
as was the case with sanofi-aventis’ Multaq,
a drug for abnormal heart rhythm called
atrial fibrillation (AFib). The FDA had
originally rejected Multaq in 2006 after
linking the therapy to a higher death rate.
In 2009, however, sanofi-aventis gained
market approval with a REMS after a study
showed a significant reduction in the rate of
hospitalizations due to AFib. In conjunction
with the launch of Multaq, the company
launched a program to assist health care
professionals in identifying appropriate
patients to ensure safe use of the product
while mitigating risks.
The REMS regulations also can be applied
to therapies that are already on the market.
For example, Centocor, Ortho Biotech
(both subsidiaries of Johnson & Johnson)
and Amgen received approval for REMS
in February 2010 for their erythropoiesisstimulating
agents (ESAs), which include
Procrit, Aranesp and Epogen. The FDA
required Amgen to develop a program
because studies showed an increase in risk
of tumor growth, heart attack, heart failure,
stroke or blood clots in patients using
ESAs. The program provides patients with
a medication guide explaining the risks and
benefits associated with using ESAs.
Outlook
At the beginning of a new decade, biotech
company pipelines show strength, but there
are still challenges and risks ahead. While
product approvals held steady in 2009, it
will be challenging for many companies to
continue to fund R&D at historic levels given
today’s tight capital market environment.
With the increase in FDA budget and
payrolls, as well as the appropriate
application of a REMS, drug manufacturers
are hoping for some relief from regulators
in the form of shorter approval times in the
years ahead.
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