Sanofi and Regeneron Pharmaceuticals, Inc. 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 per cent greater incidence in the Zaltrap arm than in the placebo arm included diarrhoea, 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 per cent of patients in the Zaltrap arm and in 1.0 per cent 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 US 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 per cent 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.

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 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.

Based in Cambridge, Massachusetts, and Vitry, France, Sanofi Oncology is dedicated to translating science into effective cancer therapeutics to address unmet medical needs for patients with cancer. Starting with a deep understanding of the mechanisms by which cancer develops, grows and spreads, the company employs innovative approaches in drug discovery, clinical development and partnerships to bring the right medicines to the right patients with the goal of helping cancer patients live healthier and longer lives.

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