The European Commission (EC) granted 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. 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, 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.

“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, 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, 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 US 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.

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).

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 tumour 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.

Sanofi Oncology is dedicated to translating science into effective therapeutics that address unmet medical needs for cancer and organ transplant patients.

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