Avastin should not be approved to treat patients with advanced breast cancer, a Food & Drug Administration (FDA) advisory panel said yesterday. The panel voted 5-4 to recommend that the FDA reject Genentech’s application to expand the approved uses of Avastin to include metastatic breast cancer patients because the drug maker was unable to prove that the benefits of the drug outweighed its serious side effects.
Avastin was approved by the FDA in 2004 to treat colon cancer, and in 2006, the agency approved it as a treatment for non-small cell lung cancer. Avastin was the first approved therapy designed to inhibit angiogenesis, the process by which new blood vessels develop and carry vital nutrients to a tumor. Avastin has been a blockbuster for Genentech, and its parent company Roche AG. For the first nine months of 2007, US sales of Avastin topped $1 billion, accounting for 27% of Genentech’s overall product sales. Some analysts believe that if Avastin is approved to treat metastatic cancer – cancer that has spread to other parts of the body – sales of the medication could grow by $1.9 billion by 2009.
But hopes that the FDA would approve Avastin for metastatic breast cancer where dimmed last week when agency staff posted documents noting that while the medication did extend the period prior to patients’ breast cancer becoming worse, treatment with the drug did not markedly increase survival time. The FDA documents also pointed out that Avastin caused serious side effects, including cardiovascular problems, bowel perforations, and a few deaths. The FDA staff said that those side effects included 5 patient deaths that were “probably or definitely” due to Avastin. While the FDA Avastin review did not include an opinion on Avastin’s breast cancer approval, the agency’s staff did recommend that the benefits of Avastin in treating breast cancer be weighed against its risks.
The FDA advisory panel had to decide whether it is valid to approve a drug that failed to extend lives, although it showed a capacity to slow tumors. The FDA sometimes approves cancer drugs on what are known as surrogate markers, such as slowing the spread of tumors, instead of waiting for survival data that can take years to collect.
Representatives from Genentech argued for the approval of Avastin as a breast cancer treatment because its effect on tumor growth could improve the quality of life for these patients, even if the drug did not extend their lives. But some FDA advisors clearly felt that this benefit did not justify Avastin’s many risks. “These patients are terminal, and it’s our job to make their lives better, not to say that it’s OK to have a stroke or that it’s manageable,” said Maha Hussain, an oncologist at the University of Michigan and the advisory panel’s chairwoman.
The FDA advisory panel vote is an indication that the agency is finally taking a tougher stance on drug approvals. Over the past few years, safety scandals involving Vioxx, Avandia and other drugs have led to criticisms that the FDA was too quick with approvals, and often ignored serious side effects.
The FDA is not obligated to follow the recommendations of its advisory panels, but usually does so. A decision on the expanded use of Avastin is expected by February.06