Sanofi-aventis and Regeneron Pharmaceuticals, Inc. announced that the phase III Velour trial evaluating the investigational agent Zaltrap (aflibercept), also known as VEGF Trap, in combination with the Folfiri chemotherapy regimen [folinic acid (leucovorin), 5-fluorouracil, and irinotecan] versus a regimen of Folfiri plus placebo met its primary endpoint of improving Overall Survival (OS) in the second-line treatment of metastatic Colorectal Cancer (mCRC)

The most frequent adverse events reported with Zaltrap in combination with Folfiri were diarrhoea, asthenia/fatigue, stomatitis and ulceration, nausea, infection, hypertension, gastrointestinal and abdominal pains, vomiting, decreased appetite, decreased weight, epistaxis, alopecia, and dysphonia.

“We are pleased with the results of the Zaltrap phase III study in this group of patients,” said Debasish Roychowdhury, MD, senior vice president and Head, Global Oncology Division, sanofi-aventis. “We are committed to bringing Zaltrap to patients with advanced colorectal cancer and maximizing the therapeutic potential of this unique and exciting medicine.”

“These findings are exciting given the limited second-line treatment options for patients with metastatic colorectal cancer,” said George D Yancopoulos, MD, PhD, chief scientific officer of Regeneron and president of Regeneron Research Laboratories. “Based upon these positive findings, we and sanofi-aventis plan to submit regulatory applications for marketing approval to the US Food and Drug Administration and the European Medicines Agency in the second half of the year.”

The Velour study was a multinational, randomized, double-blind trial comparing Folfiri in combination with either Zaltrap or placebo in the treatment of patients with mCRC after failure of an oxaliplatin-based regimen. The study enrolled 1,226 patients with mCRC who previously had been treated with an oxaliplatin-based regimen. The primary endpoint was an improvement in overall survival. The study had 90 percent power to detect a 20 percent reduction in the hazard rate for overall survival using a two-sided log-rank test. Secondary endpoints included progression-free survival, response to treatment, and safety.

Zaltrap, also known as VEGF Trap, is an investigational angiogenesis inhibitor with a unique mechanism of action. This fusion protein binds all forms of Vascular Endothelial Growth Factor-A (VEGF-A), as well as VEGF-B and Placental Growth Factor (PIGF), additional angiogenic growth factors that appear to play a role in tumour angiogenesis and inflammation.  Zaltrap has been shown to bind VEGF-A, VEGF-B, and PlGF with higher affinity than their native receptors.

Sanofi-aventis Oncology and Regeneron are collaborating on a broad oncology development program, combining the investigational agent Zaltrap with common chemotherapy regimens in the treatment of patients with advanced cancers. In addition to Velour, the programme includes one phase III trial and one phase II trial, both of which are fully enrolled: Venice: First-line treatment for hormone-refractory metastatic prostate cancer in combination with docetaxel and prednisone (phase III). An interim analysis is expected to be conducted by an Independent Data Monitoring Committee in mid 2011; final results are anticipated in 2012. Affirm: First-line treatment in metastatic colorectal cancer in combination with 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX) (phase II). Final results are expected during the second half of 2011.

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; colorectal cancer is also one of the deadliest cancers and was responsible for more than 600,000 deaths in 2008 alone. In Europe the overall survival rate is 43 percent, whereas in the United States it is 62 percent; these numbers drop considerably when the cancer spreads to distant organs. The risk of colorectal cancer increases with age – in developed countries, more than 90 percent of cases are diagnosed in individuals older than age 50.

Sanofi-Aventis Oncology is translating science into effective cancer therapeutics to address unmet medical needs for patients with cancer. The company is committed to the pursuit of science and innovative cancer therapies.

Sanofi-aventis, a leading global pharmaceutical company, discovers, develops and distributes therapeutic solutions to improve the lives of everyone.

Regeneron is a fully integrated biopharmaceutical company that discovers, develops, and commercializes medicines for the treatment of serious medical conditions.