Sanofi-aventis and Regeneron Pharmaceuticals, Inc announced that advanced ovarian cancer patients with recurrent symptomatic malignant ascites (SMA) receiving aflibercept (VEGF Trap) in a randomized, placebo-controlled phase-2 study experienced a statistically significant improvement in the primary study endpoint, mean time to first repeat paracentesis (removal of fluid from the abdominal cavity), versus placebo control. Symptomatic malignant ascites is an abnormal build-up of fluid in the abdominal cavity in patients with advanced cancer.

Mean time to first repeat paracentesis following a baseline procedure was 55 days with aflibercept as compared to 23 days for patients receiving placebo (p=0.0019). Time to first repeat paracentesis was defined as the number of days between study randomization and the first post-randomization paracentesis or, in cases where there was no repeat paracentesis, study withdrawal, death, or six months from randomization.

There was a similar incidence of deaths in both treatment groups (no statistically significant difference; hazard ratio 1.02). In this late-stage patient population with advanced ovarian cancer who were heavily pre-treated (median of four prior courses of chemotherapy), four fatal events were assessed by the investigators as aflibercept treatment related, including one case each of intestinal perforation, dyspnoea, pneumonia, and cause unknown.

The types and frequencies of adverse events reported with aflibercept in this study were generally consistent with those reported in clinical studies with other anti-VEGF therapies in advanced ovarian cancer patients.

"The results of this phase-2, placebo-controlled study demonstrate that aflibercept is a clinically active agent in patients with advanced ovarian cancer with symptomatic malignant ascites. However, given the small number of patients enrolled in this study and the fragile health status of these advanced ovarian cancer patients, who had a median survival of only about three to four months, it is difficult to definitively assess the overall clinical benefit that might be derived from treatment in the real-world clinical practice setting," stated George D Yancopoulos, president of Regeneron Research Laboratories. "Therefore, we and sanofi-aventis have decided not to submit these phase-2 data for accelerated approval in symptomatic malignant ascites. We will focus our efforts on completing the current phase-3 programme which combines aflibercept with standard chemotherapy regimens for the treatment of earlier stage metastatic colorectal, non-small cell lung, pancreatic, and prostate cancers, which should begin delivering data in 2010."

Aflibercept is an antiangiogenesis inhibitor with a unique mechanism of action. This fusion protein binds all forms of Vascular Endothelial Growth Factor-A (VEGF-A), VEGF-B, and placental growth factor (PIGF), another angiogenic growth factor that appears to play a role in tumour angiogenesis and inflammation.

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