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Publication date: 16 November 2012
Author(s): Sanofi

ZALTRAP® receives CHMP positive opinion in the European Union for previously treated mCRC

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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® (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 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, 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 asthenia.

About ZALTRAP® (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.

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