ZALTRAP® (ziv-aflibercept) Receives CHMP Positive Opinion in the
European Union for Previously Treated Metastatic Colorectal Cancer
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
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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.
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GI
perforation including fatal GI perforation can occur in patients
receiving ZALTRAP. Discontinue ZALTRAP therapy in patients who
experience GI perforation.
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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.
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WARNINGS AND PRECAUTIONS
- Patients treated with ZALTRAP® have an increased
risk of hemorrhage, including severe and sometimes fatal
hemorrhagic events.
- Monitor patients for signs and symptoms of bleeding.
- Do not initiate ZALTRAP to patients with severe
hemorrhage.
- Discontinue ZALTRAP in patients who develop severe
hemorrhage.
- GI perforation including fatal GI perforation can occur in
patients receiving ZALTRAP.
- Monitor patients for signs and symptoms of GI perforation.
- Discontinue ZALTRAP in patients who experience GI
perforation.
- Discontinue ZALTRAP in patients with compromised wound healing.
- Suspend ZALTRAP for at least 4 weeks prior to elective
surgery
- Do not initiate/resume ZALTRAP until at least 4 weeks after
surgery and surgical wound is fully healed.
- Fistula 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.
- An increased risk of Grade 3-4 hypertension has been observed
in patients receiving ZALTRAP.
- Monitor blood pressure every two weeks or more frequently and
treat with appropriate anti-hypertensive therapy during treatment
with ZALTRAP.
- Temporarily suspend ZALTRAP until hypertension is controlled,
and reduce ZALTRAP dose to 2 mg/kg for subsequent cycles.
- Discontinue ZALTRAP in patients with hypertensive crisis.
- Arterial 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.
- Severe proteinuria, nephrotic syndrome, and thrombotic
microangiopathy (TMA) occurred more frequently in patients treated
with ZALTRAP.
- Suspend ZALTRAP when proteinuria greater than or equal to 2
grams/24 hours and resume ZALTRAP when proteinuria <2 grams/24
hours.
- If recurrent, suspend until proteinuria <2 grams/24hours and
then reduce ZALTRAP dose to 2 mg/kg.
- Discontinue ZALTRAP if nephrotic syndrome or TMA develops.
- A higher incidence of neutropenic complications (febrile
neutropenia and neutropenic infection) occurred in patients
receiving ZALTRAP.
- Delay administration of ZALTRAP/FOLFIRI until neutrophil count
is greater than or equal to1.5 x 109/L.
- Incidence of severe diarrhea and dehydration is increased in
patients treated with ZALTRAP/FOLFIRI.
- The incidence of diarrhea is increased in patients greater than
or equal to 65 years of age. Monitor closely.
- Discontinue ZALTRAP in patients who develop reversible
posterior leukoencephalopathy syndrome.
ADVERSE REACTIONS
- 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 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 (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.
- Infections 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.
- In 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:
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Sanofi
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Media
Relations
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Investor Relations
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Marisol
Peron
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Sebastien
Martel
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Tel. : +
(33) 1 53 77 45 02
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Tel. : +
(33) 1 53 77 45 45
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marisol.peron@sanofi.com
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ir@sanofi.com
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Lauren
Musto
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Oncology
Division Communications
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Tel: 1
(617) 768-1993; Mobile 1(781) 572-1147
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lauren.musto@sanofi.com
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Regeneron
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Media
Relations
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Investor Relations
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Peter
Dworkin
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Manisha
Narasimhan, Ph.D.
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Tel. : 1
(914) 847-7640
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Tel. : 1
(914) 847-5126
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peter.dworkin@regeneron.com
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manisha.narasimhan@regeneron.com
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SOURCE Regeneron Pharmaceuticals, Inc.