ZALTRAP® (aflibercept) approved in the EU

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® (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 trial.

“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 ZALTRAP.”

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.

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 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 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® (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 registered 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, five-year survival is estimated to be 12 percent.

Reference

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