Genentech/Roche: FDA may still approve Avastin despite setback

An FDA advisory panel has suggested that Genentech/Roches Avastin should not receive FDA approval for metastatic breast cancer. As the FDA usually follows the panels recommendation, concerns were raised over the drugs future in this indication. However, a number of reasons may still drive US approval in metastatic breast cancer.

Genentech/Roche’s anti-angiogenic, monoclonal antibody Avastin (bevacizumab) was given a negative recommendation for metastatic breast cancer following a five-to-four vote by the Oncologic Drugs Advisory Committee (ODAC). The panel’s decision, which sent Genentech’s shares to a two-and-a-half year low, came one day after the FDA gave Avastin a negative review due to safety concerns. The drug’s fate now lies in the hands of the FDA, which will consider the panel’s recommendation in deciding whether to grant Avastin approval for metastatic breast cancer.

Avastin was the first anti-angiogenesis inhibitor to enter the oncology market. Genentech, majority-owned by Roche, holds Avastin’s marketing rights in the US, where the drug made sales of $1.7 billion in the first nine months of 2007. Avastin has been approved in the US and EU for the first-line treatment of metastatic colorectal cancer and in the US for the treatment of non-small cell lung cancer. In March 2007, Avastin was approved in the EU for the first-line treatment of metastatic breast cancer in combination with the standard chemotherapy paclitaxel.

In Avastin’s pivotal study in metastatic breast cancer, 722 patients received paclitaxel or paclitaxel in combination with Avastin. Avastin was shown to extend progression-free survival by 5.5 months, but not overall survival. However, patients in the Avastin group had a 20% increase in serious side effects including hypertension, blood clots and heart attacks.

In the drug’s recent review, FDA staff suggested that the improvement in progression-free survival should be weighted against the potentially fatal toxicity. The advisory panel, made up largely of practicing physicians, had been expected to look more kindly on the drug than FDA staff. The FDA, which usually follows the advisory panel’s advice, will now consider the panel’s negative recommendation in deciding whether to approve Avastin for breast cancer.

Avastin is already used off-label in the US for metastatic breast cancer. However, FDA approval would allow the drug to be promoted for this indication and help secure reimbursement by insurers. If approval is granted, Avastin is expected to change the first-line treatment of metastatic breast cancer.

Despite ODAC’s negative recommendation and irrespective of its questionable toxicity profile, the FDA is likely to approve Avastin despite only achieving an incremental improvement in progression-free survival. Avastin’s approval in the EU for breast cancer, its extensive off-label use in breast cancer in the US, and the high patient and physician awareness may all force a positive FDA decision.