ZALTRAP® (aflibercept) Approved in the EU for Patients with Previously Treated Metastatic Colorectal Cancer

PR Newswire/Les Echos/ 
ZALTRAP(r) (aflibercept) Approved in the EU for Patients with Previously Treated
Metastatic Colorectal Cancer 
- First and only agent to statistically significantly improve survival in
combination with FOLFIRI chemotherapy after an oxaliplatin regimen - 
Paris, France and Tarrytown, NY - February 5, 2013 - Sanofi (EURONEXT: SAN and
NYSE: SNY) and Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced
that the European Commission (EC) granted marketing authorization in the
European Union 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. This
decision was based on the efficacy and safety results of the VELOUR Phase III
"ZALTRAP is an important addition to the metastatic colorectal cancer treatment
landscape and helps to fill a critical treatment gap," said Eric Van Cutsem,
M.D., Ph.D., University Hospitals Leuven, Belgium and lead investigator of the
VELOUR study. "ZALTRAP is the first and only agent to demonstrate a statistical
survival improvement in a Phase III trial in patients previously treated with an
oxaliplatin-based regimen who are being treated with FOLFIRI for their
metastatic disease." 
In Europe, colorectal cancer is the most common cancer in both men and women and
is the second leading cause of cancer death. In 2008, there were 436,000 new
cases diagnosed and 212,000 deaths from colorectal cancer.(1) 
"I would like to thank the physicians, patients and their families for their
support in moving ZALTRAP through the clinical trial process leading to approval
in Europe," said Debasish Roychowdhury, M.D., Senior Vice President and Head,
Sanofi Oncology. "We are thrilled to provide a new therapy that further extends
the lives of patients with metastatic colorectal cancer and look forward to
working with European health authorities to ensure patients have access to
Commenting on the marketing authorization, George D. Yancopoulos, M.D., Ph.D.,
Chief Scientific Officer of Regeneron and President of Regeneron Research
Laboratories, added: "The European approval of ZALTRAP provides a new option to
address the unmet medical need in this patient population. There continues to be
a need to develop new cancer therapies, and Regeneron and Sanofi are committed
to finding novel investigational treatments and combinations." 
ZALTRAP received approval from the U.S. Food and Drug Administration (FDA) in
August 2012 after a Priority Review, and marketing authorization applications
for ZALTRAP are under review with other regulatory agencies worldwide. 
(1) ESMO Consensus Guidelines for management of pateints with colon and rectal
cancer. A personalized approach to clinical decision making. Annals of Oncol.
2012; 23: 2470-2516 
About the VELOUR Phase III Study
The ZALTRAP approval was based on data from the pivotal Phase III VELOUR trial,
a 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
oxaliplatin-containing regimen. Twenty-eight percent of patients in the study
received prior bevacizumab therapy. The primary endpoint of the trial 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 f rom 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 alone (p=0.0001). 
The most common adverse reactions (all grades, ≥20% incidence) reported at a
higher incidence (2% or greater between-arm difference) in the ZALTRAP/FOLFIRI
arm, in order of decreasing frequency, were leukopenia, 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 (≥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, leukopenia,
stomatitis, fatigue, proteinuria, and asthenia. 
About ZALTRAP(r) (aflibercept)
ZALTRAP is a recombinant fusion protein which acts as a decoy receptor that
binds to Vascular Endothelial Growth Factor-A (VEGF-A), VEGF-B and placental
growth factor (PIGF), as shown in preclinical studies. 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 US,
ZALTRAP is a reg istered trademark of Regeneron Pharmaceuticals, Inc. 
In the US ZALTRAP is approved with the US proper name ziv-aflibercept. The World
Health Organization (WHO) recommended international non-proprietary name for
ZALTRAP is aflibercept. Marketing authorization applications for ZALTRAP are
under review other regulatory agencies worldwide. 
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, f ive-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 10 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 leading science-based biopharmaceutical company based in
Tarrytown, New York that discovers, invents, develops, manufactures, and
commercializes medicines for the treatment of serious medical conditions.
Regeneron markets medicines for eye diseases, colorectal cancer, and a rare
inflammatory condition and has product candidates in development in other areas
of high unmet medical need, including hypercholesterolemia, rheumatoid
arthritis, asthma and atopic dermatitis. For additional information about the
company, please visit 
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Regeneron Forward-Looking Statements
This news release includes forward-looking statements that involve risks and
uncertainties relating to future events and the future performance of Regeneron,
and actual events or results may differ materially from these forward-looking
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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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and timing of possible regulatory approval and commercial launch of Regeneron's
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result of new information, future events, or otherwise, unless required by
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                      Michael Aberman, M.D.
Tel. : 1 (914) 345-7640            Tel. : 1 (914) 847-7799 
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-0- Feb/05/2013 08:24 GMT
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