ZALTRAP™ (aflibercept) significantly improved survival in previously treated metastatic colorectal cancer patients

Sanofi (EURONEXT: SAN and NYSE: SNY) and Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN) today announced that data showing that the investigational agent ZALTRAP™ (aflibercept), also known as VEGF Trap, significantly improved survival in previously treated metastatic colorectal cancer patients will be presented at the ESMO World Congress on Gastrointestinal Cancer on June 25, 2011. The abstract (#0-0024) was published in the June 2011 supplement to Annals of Oncology.

Patients with metastatic colorectal cancer (mCRC) previously treated with oxaliplatin were randomized to receive ZALTRAP™ or placebo in combination with the FOLFIRI regimen (irinotecan-5-fluorouracil-leucovorin). The addition of ZALTRAP™ to the FOLFIRI regimen significantly improved both overall survival (HR=0.817; p=0.0032) and progression-free survival (HR=0.758; p=0.00007). A similar effect was seen with ZALTRAP™ therapy whether or not patients had received prior bevacizumab therapy.

Grade 3 or 4 adverse events (AEs) that occurred with a more than 2 percent greater incidence in the ZALTRAP™ arm than in the placebo arm included diarrhea, asthenia/fatigue, stomatitis/ulceration, infections, hypertension, GI/abdominal pains, neutropenia, neutropenic complications and proteinuria. Deaths on study treatment due to AEs occurred in 2.6 percent of patients in the ZALTRAP™ arm and in 1.0 percent of patients in the placebo arm.

“We are excited by these results and are committed to bringing this novel therapy to patients as soon as possible,” said Debasish Roychowdhury, M.D., Senior Vice President and Head, Sanofi Oncology. “We plan to submit regulatory applications for marketing approval to the U.S. Food and Drug Administration and the European Medicines Agency in the second half of the year.”

“These results highlight the potential utility of our novel anti-VEGF therapy in cancer settings where there continue to be significant medical need,” said George D. Yancopoulos, M.D., Ph.D., Chief Scientific Officer of Regeneron and President of Regeneron Research Laboratories. “We look forward to further developing ZALTRAP™ using innovative combinations that can help advance the management of patients with cancer.”

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. The study randomized 1,226 patients with mCRC who previously had been treated with an oxaliplatin-based regimen. Approximately 30 percent of patients in the trial received prior bevacizumab therapy. The primary endpoint was an improvement in overall survival. Secondary endpoints included progression-free survival, response to treatment, and safety.

About ZALTRAP™ (aflibercept) and the Clinical Development Program

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 tumor angiogenesis and inflammation. ZALTRAP™ has been shown to bind VEGF-A, VEGF-B, and PlGF with higher affinity than their native receptors.

Sanofi 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 program 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.

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. Colorectal cancer is 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.