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

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

PR Newswire

PARIS and TARRYTOWN, N.Y., Nov. 16, 2012

PARIS and TARRYTOWN, N.Y., Nov. 16, 2012 /PRNewswire/ --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^® (ziv-aflibercept)
Injection for Intravenous 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
trial.

"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 after Priority Review and marketing authorization applications for
ZALTRAP are under review with other regulatory agencies worldwide. In the
U.S. ZALTRAP is approved with the U.S. proper name ziv-aflibercept for use in
combination with 5-fluorouracil, leucovorin, irinotecan (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 the VELOUR Phase 3 Study
The VELOUR trial was a Phase 3 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 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 asthenia.

About ZALTRAP^® (ziv-aflibercept) Injection for Intravenous Infusion
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.

Important Safety Information for ZALTRAP from the U.S. Prescribing Information

WARNING: HEMORRHAGE, GASTROINTESTINAL PERFORATION, COMPROMISED WOUND HEALING
Severe and sometimes fatal hemorrhage, including gastrointestinal (GI)
hemorrhage, has been reported in the patients who have received ZALTRAP in
combination with FOLFIRI. Monitor patients for signs and symptoms of GI
bleeding and other severe bleeding. Do not administer ZALTRAP to patients
with severe hemorrhage.
GI perforation including fatal GI perforation can occur in patients receiving
ZALTRAP. Discontinue ZALTRAP therapy in patients who experience GI
perforation.
Severe compromised wound healing can occur in patients receiving
ZALTRAP/FOLFIRI. Discontinue ZALTRAP in patients with compromised wound
healing. Suspend ZALTRAP for at least 4 weeks prior to elective surgery, and
do not resume ZALTRAP for at least 4 weeks following major surgery and until
the surgical wound is fully healed.

WARNINGS AND PRECAUTIONS

  oPatients treated with ZALTRAP^® have an increased risk of hemorrhage,
    including severe and sometimes fatal hemorrhagic events.

       oMonitor patients for signs and symptoms of bleeding.
       oDo not initiate ZALTRAP to patients with severe hemorrhage.
       oDiscontinue ZALTRAP in patients who develop severe hemorrhage.

  oGI perforation including fatal GI perforation can occur in patients
    receiving ZALTRAP.

       oMonitor patients for signs and symptoms of GI perforation.
       oDiscontinue ZALTRAP in patients who experience GI perforation.

  oDiscontinue ZALTRAP in patients with compromised wound healing.

       oSuspend ZALTRAP for at least 4 weeks prior to elective surgery
       oDo not initiate/resume ZALTRAP until at least 4 weeks after surgery
         and surgical wound is fully healed.

  oFistula formation involving GI and non-GI sites occurs at a higher
    incidence in patients treated with ZALTRAP. Discontinue ZALTRAP therapy
    in patients who develop fistula.
  oAn increased risk of Grade 3-4 hypertension has been observed in patients
    receiving ZALTRAP.

       oMonitor blood pressure every two weeks or more frequently and treat
         with appropriate anti-hypertensive therapy during treatment with
         ZALTRAP.
       oTemporarily suspend ZALTRAP until hypertension is controlled, and
         reduce ZALTRAP dose to 2 mg/kg for subsequent cycles.
       oDiscontinue ZALTRAP in patients with hypertensive crisis.

  oArterial thromboembolic events (ATE), including transient ischemic attack,
    cerebrovascular accident, and angina pectoris, occurred more frequently in
    patients who have received ZALTRAP. Discontinue ZALTRAP in patients who
    experience an ATE.
  oSevere proteinuria, nephrotic syndrome, and thrombotic microangiopathy
    (TMA) occurred more frequently in patients treated with ZALTRAP.

       oSuspend ZALTRAP when proteinuria greater than or equal to 2 grams/24
         hours and resume ZALTRAP when proteinuria <2 grams/24 hours.
       oIf recurrent, suspend until proteinuria <2 grams/24hours and then
         reduce ZALTRAP dose to 2 mg/kg.
       oDiscontinue ZALTRAP if nephrotic syndrome or TMA develops.

  oA higher incidence of neutropenic complications (febrile neutropenia and
    neutropenic infection) occurred in patients receiving ZALTRAP.

       oDelay administration of ZALTRAP/FOLFIRI until neutrophil count is
         greater than or equal to1.5 x 10^9/L.

  oIncidence of severe diarrhea and dehydration is increased in patients
    treated with ZALTRAP/FOLFIRI.

       oThe incidence of diarrhea is increased in patients greater than or
         equal to 65 years of age. Monitor closely.

  oDiscontinue ZALTRAP in patients who develop reversible posterior
    leukoencephalopathy syndrome.

ADVERSE REACTIONS

  oThe 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 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.
  oThe 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, leukopenia, stomatitis, fatigue,
    proteinuria, and asthenia.
  oInfections occurred at a higher frequency in patients receiving
    ZALTRAP/FOLFIRI (46%, all grades; 12%, Grade 3-4) than in patients
    receiving placebo/FOLFIRI (33%, all grades; 7%, Grade 3-4), including
    urinary tract infection, nasopharyngitis, upper respiratory tract
    infection, pneumonia, catheter site infection, and tooth infection.
  oIn patients with mCRC, venous thromboembolic events (VTE), consisting
    primarily of deep venous thrombosis and pulmonary embolism, occurred in 9%
    of patients treated with ZALTRAP/FOLFIRI and 7% of patients treated with
    placebo/FOLFIRI.

Please click here for full U.S. Prescribing Information for ZALTRAP
(ziv-aflibercept) Injection for Intravenous Infusion, including Boxed WARNING,
and visit: www.ZALTRAP.com

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 agents.

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^® (aflibercept) Injection, ZALTRAP^®
(ziv-aflibercept) Injection for Intravenous Infusion, and ARCALYST^®
(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 www.regeneron.com.

Sanofi Forward Looking Statements
This press release contains forward-looking statements as defined in the
Private Securities Litigation Reform Act of 1995, as amended. Forward-looking
statements are statements that are not historical facts. These statements
include projections and estimates and their underlying assumptions, statements
regarding plans, objectives, intentions and expectations with respect to
future financial results, events, operations, services, product development
and potential, and statements regarding future performance. Forward-looking
statements are generally identified by the words "expects", "anticipates",
"believes", "intends", "estimates", "plans" and similar expressions. Although
Sanofi's management believes that the expectations reflected in such
forward-looking statements are reasonable, investors are cautioned that
forward-looking information and statements are subject to various risks and
uncertainties, many of which are difficult to predict and generally beyond the
control of Sanofi, that could cause actual results and developments to differ
materially from those expressed in, or implied or projected by, the
forward-looking information and statements. These risks and uncertainties
include among other things, the uncertainties inherent in research and
development, future clinical data and analysis, including post marketing,
decisions by regulatory authorities, such as the FDA or the EMA, regarding
whether and when to approve any drug, device or biological application that
may be filed for any such product candidates as well as their decisions
regarding labelling and other matters that could affect the availability or
commercial potential of such product candidates, the absence of guarantee that
the product candidates if approved will be commercially successful, the future
approval and commercial success of therapeutic alternatives, the Group's
ability to benefit from external growth opportunities, trends in exchange
rates and prevailing interest rates, the impact of cost containment policies
and subsequent changes thereto, the average number of shares outstanding as
well as those discussed or identified in the public filings with the SEC and
the AMF made by Sanofi, including those listed under "Risk Factors" and
"Cautionary Statement Regarding Forward-Looking Statements" in Sanofi's annual
report on Form 20-F for the year ended December 31, 2011. Other than as
required by applicable law, Sanofi does not undertake any obligation to update
or revise any forward-looking information or statements.

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 statements. These statements concern, and these risks and
uncertainties include, 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^® (ziv-aflibercept), unforeseen safety issues resulting
from the administration of products and product candidates in patients, the
likelihood and timing of possible regulatory approval and commercial launch of
Regeneron's late-stage product candidates, determinations by regulatory and
administrative governmental authorities which may delay or restrict
Regeneron's ability to continue to develop or commercialize Regeneron's
products and drug candidates, competing drugs that may be superior to
Regeneron's products and drug candidates, uncertainty of market acceptance of
Regeneron's products and drug candidates, unanticipated expenses, the costs of
developing, producing, and selling products, the potential for any license or
collaboration agreement, including Regeneron's agreements with Sanofi and
Bayer HealthCare, to be canceled or terminated, and risks associated with
third party intellectual property and pending or future litigation relating
thereto. A more complete description of these and other material risks can be
found in Regeneron's filings with the United States Securities and Exchange
Commission, including its Form 10-K for the year ended December 31, 2011 and
its Form 10-Q for the quarter ended September 30, 2012. Regeneron does not
undertake any obligation to update publicly any forward-looking statement,
whether as a result of new information, future events, or otherwise, unless
required by law.

Contacts:
Sanofi
Media Relations                               Investor Relations
Marisol Peron                                 Sebastien Martel
Tel. : + (33) 1 53 77 45 02                   Tel. : + (33) 1 53 77 45 45
marisol.peron@sanofi.com                      ir@sanofi.com
Lauren Musto
Oncology Division Communications
Tel: 1 (617) 768-1993; Mobile 1(781) 572-1147
lauren.musto@sanofi.com
Regeneron
Media Relations                               Investor Relations
Peter Dworkin                                 Manisha Narasimhan, Ph.D.
Tel. : 1 (914) 847-7640                       Tel. : 1 (914) 847-5126
peter.dworkin@regeneron.com                  manisha.narasimhan@regeneron.com



SOURCE Regeneron Pharmaceuticals, Inc.

Website: http://www.regeneron.com
 
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