Sanofi-aventis and Regeneron Pharmaceuticals, Inc. provided an update on the clinical development programme for aflibercept, including results from a phase II study in advanced ovarian cancer.

The companies also announced that six abstracts describing the results of clinical trials with aflibercept will be presented at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO) and an additional two abstracts were summarized in the ASCO proceedings.

Vascular Endothelial Growth Factor (VEGF), is being developed by sanofi-aventis and Regeneron for the treatment of several types of cancer.

Sanofi-aventis and Regeneron currently are enrolling patients in the US, Europe, and other countries around the world, in four phase III studies in approximately 1200 patients that combine aflibercept with standard chemotherapy regimens: 2nd-line treatment for metastatic colorectal cancer in combination with folinic acid, 5-FU, and irinotecan; 1st-line treatment for metastatic pancreatic cancer in combination with gemcitabine; 1st-line treatment for metastatic androgen- independent prostate cancer in combination with docetaxel and prednisone; 2nd-line treatment for metastatic non-small cell lung cancer in combination with docetaxel.

A phase 2 1st-line study of aflibercept in metastatic colorectal cancer in combination with folinic acid, 5- FU, and oxaliplatin is expected to begin later this year.

The companies reported results of a randomized, double-blind, phase 2 study of 215 women with advanced ovarian cancer who were treated with aflibercept at a dose of 2 milligrams per kilogram (mg/kg) or 4 mg/kg every two weeks. Response to treatment was assessed both by the clinical investigators and an independent review committee (IRC). As assessed by the investigators, RECIST (Response Evaluation Criteria in Solid Tumours) response rates were 7.3 per cent with the 4 mg/kg dose and 3.8 per cent with the 2 mg/kg dose. As assessed by the IRC, patients achieved a response rate according to RECIST criteria of 4.6 per cent in the 4 mg/kg arm and 0.9 per cent in the 2 mg/kg arm.

The study did not achieve its primary endpoint of demonstrating that patients in either arm of the study achieved a RECIST response rate as assessed by the IRC that was statistically significantly greater than 5 per cent. The results were consistent with the interim data of the same trial reported at the 2007 ASCO meeting.

CA-125 response, an important marker of disease activity in ovarian cancer, was a key secondary endpoint of the study. Response rates, defined as at least a 50% reduction in CA-125 protein levels, were 11.6 per cent in the evaluable patients treated with 4 mg/kg and 11.5 per cent in the evaluable patients treated with 2 mg/kg. Eighteen (13.8%) of the130 CA-125 response-evaluable patients from both dose groups had either a RECIST (as assessed by the IRC) or CA-125 response.

In the entire study population, as assessed by the IRC, median progression-free survival was 13.3 and 13.0 weeks with the 4 mg/kg and 2 mg/kg doses, respectively. Median overall survival was 49.3 and 55.4 weeks with the 4 mg/kg and 2 mg/kg doses, respectively.

Of the 40 patients in both dose groups who had evaluable ascites at baseline, 77.5 per cent had either a complete disappearance or stabilization of their ascites over the study period as per investigators review.

Side effects of treatment with aflibercept were typical of this class of anti-angiogenic agents, with hypertension being the most common grade 3/4 adverse event. Other grade 3/4 adverse e vents occurring in at least 5% of patients included abdominal pain, anorexia, arthralgia, asthenia, diarrhoea, dysphonia, fatigue, headache, proteinuria, and vomiting. Bowel perforations were observed in 1.8 per cent of patients. There were no significant differences in safety between the dose groups.

"We are encouraged by the results reported with the use of single-agent aflibercept in this advanced ovarian cancer patient population for whom few therapeutic options are available," stated Dr Marc Cluzel, Senior vice president, R&D of sanofi-aventis.

"We and sanofi-aventis are continuing to evaluate the data from this trial in order to determine the next steps for aflibercept in advanced ovarian cancer," commented George D. Yancopoulos, M.D., Ph.D., President of Regeneron Research Laboratories.