Conditional approval aims to speed the delivery of drugs to patients in need. But when full approval is denied, complications arise for patients, companies and regulatory agencies alike.

In 2008, Avastin (Genentech) was conditionally approved for the treatment of metastatic breast cancer through the US Food and Drug Administration’s (FDA) accelerated approval process. Approval was based on the results of the phase 3 E2100 trial, which showed that treatment with Avastin plus paclitaxel conferred a 5.5-month increase in median progression-free survival (PFS) over treatment with paclitaxel alone. In the conditional approval letter for Avastin, the FDA stated that follow-up trials were required to “further define the degree of clinical benefit to patients” for conversion to full approval.

But the next two phase 3 trials of Avastin in breast cancer patients—AVADO and RIBBON1—showed more modest increases in median PFS (0.9–2.9 months). Moreover, a fourth trial, AVF2119g, of capecitabine with or without Avastin, showed no improvement in PFS in the Avastin arm. These results—coupled with what the FDA contends to be increased risks of serious side effects associated with Avastin in combination with standard chemotherapy and no increase in overall survival—led the agency to recommend in December 2010 that the approval of Avastin for breast cancer (but not for other indications) be withdrawn.

On June 29, following a two-day hearing requested by Genentech, the FDA oncologic drugs advisory committee voted unanimously against the continued approval of Avastin for the treatment of metastatic breast cancer. A final decision will be made by the FDA commissioner, Margaret Hamburg, some time after the close of the public comment period on July 28.

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