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GEN News Highlights : Mar 11, 2011

Regeneron and Sanofi-Aventis Cancer Drug Misses Phase III Primary Endpoint but Meets Secondary Targets

Pivotal trials in colorectal and prostate cancers are ongoing, with results expected in 2011 and 2012.

Regeneron Pharmaceuticals and partner sanofi-aventis Oncology reported topline Phase III trial data showing that the addition of aflibercept (VEGF Trap) to chemotherapy for the second-line treatment of non-small-cell lung cancer (NSCLC) had no impact on overall survival compared with chemotherapy alone. However, the Vital study found that aflibercept did improve the key secondary endpoint of progression-free survival when added to chemotherapy. Moreover, the overall objective response rate was 23.3% for the aflibercept cohort, compared with 8.9% for the group receiving chemotherapy plus placebo, the firms stress. Adverse events leading to discontinuation of therapy occurred in 27.2% of aflibercept-treated patients compared with 14.6% of those in the placebo arm.

The Vital study evaluated docetaxel chemotherapy plus either aflibercept or placebo, in the treatment of locally advanced or metastatic non-squamous NSCLC in 913 patients who had failed one platinum-based therapy.

The firms say they will now carry out a detailed analysis of the trial’s efficacy and safety data. “Bringing new and innovative cancer therapies to patients can be incredibly challenging, especially in difficult-to-treat cancers such as second-line NSCLC,” admits Debasish Roychowdhury, svp and head of global oncology at sanofi-aventis.

Regeneron and sanofi-aventis are developing aflibercept for use in combination with chemotherapy against a number of cancers. Two additional Phase III studies and a Phase II trial are ongoing. The Phase III Velour trial is investigating the candidate in combination with FOLFIRI chemotherapy in the treatment of metastatic colorectal cancer. Trial results are anticipated during the first half of 2011. The Phase III Venice study is evaluating aflibercept in combination with docetaxel and prednisone for the first-line treatment of hormone-refractory metastatic prostate cancer. An interim analysis by the trial’s independent data monitoring committee should be carried out in mid-2011, and final trial data is expected in 2012, the firms note. The Phase II Affirm trial, meanwhile, is investigating aflibercept combined with FOLFOX chemotherapy as first-line treatment of metastatic colorectal cancer. Final results from this study are expected during the second half of 2011.

Originally developed by Regeneron, Aflibercept is an angiogenesis inhibitor fusion protein that binds all forms of VEGF-A, as well as VEGF-B and placental growth factor (PlGF). The firm has separately partnered with Bayer HealthCare for clinical development of an ophthalmic formulation of the aflibercept for the treatment of eye disorders, including wet age-related macular degeneration (AMD), diabetic macular edema (DME) and central retinal vein occlusion. Under terms of the firms’ licensing and commercialization agreement, Bayer HealthCare will market the VEGF Trap-Eye product outside the U.S., where the companies will also share equally in sales profits.  Regeneron maintains exclusive rights to VEGF Trap-Eye in the U.S.

Just last month Regeneron submitted a BLA to FDA for the use of VEGF Trap-Eye as a treatment for wet AMD. At the time it said Bayer HealthCare also expects to submit regulatory applications in Europe during the first half of this year.

In January Regeneron Bayer HealthCare teamed up with Singapore Eye Research Institute to start a new Phase III study evaluating VEGF Trap-Eye in patients with choroidal neovascularisation of the retina as a result of pathologic myopia. The trial has been initiated in Japan and other Asian countries, including China, Korea, Singapore, and Taiwan.

Positive data from one of two Phase III trial evaluating VEGF Trap-Eye in patients with macular edema due to central retinal vein occlusion were reported in December 2010. A second Phase III study is ongoing. Also in December the firms released positive results from a Phase II study evaluating the treatment in patients with DME.