ZALTRAP® (aflibercept) Receives CHMP Positive Opinion in the European Union for Previously Treated Metastatic Colorectal

PR Newswire/Les Echos/ 
 ZALTRAP(r) (aflibercept) Receives CHMP Positive Opinion in the European Union 
        for Previously Treated Metastatic Colorectal Cancer 
Paris, France and Tarrytown, NY - November 16, 2012 - Sanofi (EURONEXT: SAN and
NYSE: SNY) and Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced
that the Committee for Medicinal Products for Human Use (CHMP) of the European
Medicines Agency (EMA) adopted a positive opinion and recommended the granting
of marketing authorization for ZALTRAP(r) (aflibercept) 25mg/ml concentrate for
solution for infusion in combination with irinotecan/5-fluorouracil/folinic acid
(FOLFIRI) chemotherapy in adults with metastatic colorectal cancer (mCRC) that
is resistant to or has progressed after an oxaliplatin-containing regimen. 
The European Commission now needs to ratify the positive opinion from CHMP to
grant marketing authorization of ZALTRAP in all 27 European Union member
countries. A decision is expected from the European Commission in the first
quarter of 2013. The CHMP opinion was based on data from the pivotal VELOUR
"We are pleased that CHMP has supported our ZALTRAP application. This brings us
one step closer to bringing this novel treatment with a proven survival benefit
to colorectal cancer patients in Europe," said Debasish Roychowdhury, M.D.,
Senior Vice President and Head, Sanofi Oncology. 
"It is gratifying to see the years of effort that went into designing and
developing the angiogenesis inhibitor ZALTRAP translate into a clinical benefit
for patients with metastatic colorectal cancer that has progressed on prior
therapy," said George D. Yancopoulos, M.D., Ph.D., Chief Scientific Officer of
Regeneron and President of Regeneron Laboratories. "ZALTRAP is the only agent
that has demonstrated a statistically significant improvement in overall
survival in combination with FOLFIRI versus FOLFIRI alone in patients who
progressed on a prior oxaliplatin-containing regimen." 
ZALTRAP received approval from the U.S. Food and Drug Administration (FDA) in
August 2012, and marketing authorization applications for ZALTRAP are under
review with other regulatory agencies worldwide. 
About the VELOUR Phase III Study
The VELOUR trial was a Phase III multinational, randomized, double-blind trial
comparing FOLFIRI in combination with either ZALTRAP or placebo in the treatment
of patients with mCRC. The study randomized 1,226 patients with mCRC who
previously had been treated with an oxaliplatincontaining regimen. Twenty-eight
percent of patients in the study received prior bevacizumab therapy. The primary
endpoint was overall survival. Secondary endpoints included progression-free
survival, overall response rate, and safety 
The VELOUR trial showed that in patients previously treated with an
oxaliplatin-containing regimen, adding ZALTRAP to FOLFIRI significantly improved
median survival from 12.06 months to 13.50 months (HR=0.817 [95% CI 0.714 to
0.935]; p=0.0032, an 18 percent relative risk reduction. A significant
improvement in progression-free survival from 4.67 months to 6.90 months
(HR=0.758 [95% CI 0.661 to 0.869]; p=0.00007), a 24 percent relative risk
reduction, was also observed. The overall response rate in the ZALTRAP plus
FOLFIRI arm was 19.8% vs. 11.1% for FOLFIRI (p=0.0001). 
The most common adverse reactions (all grades, greater than or equal to 20%
incidence) reported at a higher incidence (2% or greater between-arm difference)
in the ZALTRAP-FOLFIRI arm, in order of decreasing frequency, were leucopenia,
diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue,
thrombocytopenia, ALT increased, hypertension, weight decreased, decreased
appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and
headache. The most common Grade 3-4 adverse reactions (greater than or equal to
5%) reported at a higher incidence (2% or greater between-arm difference) in the
ZALTRAP-FOLFIRI arm, in order of decreasing frequency, were neutropenia,
diarrhea, hypertension, leucopenia, stomatitis, fatigue, proteinuria, and
About ZALTRAP(r) (aflibercept)
ZALTRAP is recombinant fusion protein that binds the angiogenic proteins
Vascular Endothelial Growth Factor-A (VEGF-A), VEGF-B and placental growth
factor (PIGF). VEGF-A is one of the mediators contributing to angiogenesis.
VEGF-B and PlGF, related growth factors in the VEGF family, may contribute to
tumor angiogenesis as well. In the U.S., ZALTRAP is a registered trademark of
Regeneron Pharmaceuticals, Inc. 
In the U.S. ZALTRAP is approved with the U.S. proper name ziv-aflibercept for
use in combination with FOLFIRI, in patients with metastatic colorectal cancer
(mCRC) that is resistant to or has progressed following an
oxaliplatin-containing regimen. The World Health Organization (WHO) recommended
international non-proprietary name for ZALTRAP is aflibercept. 
About Colorectal Cancer
Worldwide, colorectal cancer is the third most commonly diagnosed cancer in
males and the second most in females, with more than 1.2 million new cases
diagnosed in 2008. One of the deadliest cancers, colorectal cancer was
responsible for more than 600,000 deaths globally in 2008 alone. According to
the American Cancer Society, approximately 60 percent of colorectal cancer cases
are diagnosed at the locally advanced or metastatic stage. Although survival for
early stage disease is relatively high, once colorectal cancer metastasizes to
distant organs, five-year survival is estimated to be 12 percent. 
About Sanofi Oncology
Based in Cambridge, Massachusetts, USA and Vitry, France, Sanofi Oncology is
dedicated to translating science into effective therapeutics that address unmet
medical needs for cancer and organ transplant patients. Starting with a deep
understanding of the disease and the patient, Sanofi Oncology employs innovative
approaches to drug discovery and clinical development, with the ultimate goal of
bringing the right medicines to the right patients to help them live healthier
and longer lives. We believe in the value of partnerships that combine our
internal scientific expertise with that of industry and academic experts. Our
portfolio includes 11 marketed products and more than 15 investigational
compounds in clinical development, including small molecules and biological
About Sanofi
Sanofi, a global and diversified healthcare leader, discovers, develops and
distributes therapeutic solutions focused on patients' needs. Sanofi has core
strengths in the field of healthcare with seven growth platforms: diabetes
solutions, human vaccines, innovative drugs, consumer healthcare, emerging
markets, animal health and the new Genzyme. Sanofi is listed in Paris (EURONEXT:
SAN) and in New York (NYSE: SNY). 
About Regeneron Pharmaceuticals, Inc.
Regeneron is a fully integrated biopharmaceutical company that discovers,
invents, develops, manufactures, and commercializes medicines for the treatment
of serious medical conditions. Regeneron markets three products in the United
States, EYLEA(r) (aflibercept) Injection, ZALTRAP(r) (ziv-aflibercept) Injection
for Intravenous Infusion, and ARCALYST(r) (rilonacept) Injection for
Subcutaneous Use; ZALTRAP is co-commercialized with Sanofi. Phase 3 studies are
in progress with EYLEA in two additional indications and with product candidates
sarilumab and REGN727. Regeneron has active research and development programs in
many disease areas, including ophthalmology, inflammation, cancer, and
hypercholesterolemia. Additional information and recent news releases are
available on the Regeneron web site at 
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among others, the nature, timing, and possible success and therapeutic
applications of Regeneron's products, product candidates and research and
clinical programs now underway or planned, including without limitation
ZALTRAP(r) (ziv-aflibercept), unforeseen safety issues resulting from the
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publicly any forward-looking statement, whether as a result of new information,
future events, or otherwise, unless required by law. 
Media Relations                               Investor Relations
Marisol Péron                                 Sébastien Martel
Tél. : + (33) 1 53 77 45 02                   Tél. : + (33) 1 53 77 45 45             
Lauren Musto
Oncology Division Communications
Tel: 1 (617) 768-1993; Mobile 1(781) 572-1147  
Media Relations                               Investor Relations
Peter Dworkin                                 Manisha Narasimhan, Ph.D.
Tel. : 1 (914) 345-7640                       Tel. : 1 (914) 847-5126      
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-0- Nov/16/2012 13:18 GMT
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