FDA: No to Breast Cancer Drug, Could Cost Genetech $1 Billion

By Gene Quinn
December 16, 2010

The U.S. Food and Drug Administration announced today that it is recommending that Avastin® (bevacizumab) lose its breast cancer indication from the label because the drug has not been shown to be safe and effective for that use. This preliminary decision by the FDA is sure to spark enormous controversy because the European Medicines Agency, who likewise issued an announcement regarding Avastin® today, determined that the drug can and should remain on the market in Europe. In fact, the European Medicines Agency has confirmed that the benefits of Avastin® in combination with paclitaxel outweigh the risks, further determining that the combination of Avastin® and paclitaxel remains a valuable treatment option for patients suffering from metastatic breast cancer. If the FDA is successful in removing the breast cancer indication from Avastin® Genentech (a member of the Roche Group and the maker of Avastin®) could lose $1 billion of its $6 billion in annual sales of Avastin® due to the lost sales associated with use to treat breast cancer.

Avastin® is an anticancer medicine which contains the active substance bevacizumab. It is used in combination with other anticancer treatments to treat cancers of the colon, rectum, lung, kidney or breast. Avastin®, in combination with chemotherapy (paclitaxel), was approved in the United States in February 2008 under the FDA’s accelerated approval program, based on the results of a clinical trial known as “E2100,” which evaluated the drug in patients who had not received chemotherapy for their metastatic HER2-negative breast cancer. Under the accelerated approval program, a drug may be approved based on clinical data that suggest the drug has a meaningful clinical benefit, with more information being needed to confirm. After the accelerated approval of Avastin® for breast cancer, Genentech completed additional clinical trials and submitted the data from those studies to the FDA. The FDA believed that the data showed only a small effect on progression-free survival (i.e., (how long the patients lived without their disease getting worse) and no evidence of an improvement in overall survival or a clinical benefit to patients sufficient to outweigh the risks. According to the FDA, Avastin® has been associated with serious and potentially life-threatening side effects including the risk of stroke, heart failure, wound healing complications, organ damage or failure; and the development of a neurological condition called reversible posterior leukoencephalopathy syndrome (RPLS), characterized by high blood pressure, headaches, confusion, seizures, and vision loss from swelling of the brain.

[Bio-Pharma]

The FDA announcement explained earlier today that it is making the recommendation to remove the breast cancer indication from the label of Avastin® after the results of four clinical studies of Avastin® in women with breast cancer indicate that the drug does not prolong overall survival in breast cancer patients or provide a sufficient benefit in slowing disease progression to outweigh the significant risk to patients. To the contrary, the European Medicines Agency decided the exact opposite, at least with respect to Avastin® in combination with paclitaxel.

Combination therapy of Avastin® and docetaxel for metastatic breast cancer was approved in Europe in September 2009 on the basis of data that showed a small but significant increase in progression-free survival and no detrimental effect on overall survival. However, new data submitted to the European Medicines Agency created some uncertainty about the effect on overall survival. The new data also questioned the size of the effect on progression-free survival, which appeared to be smaller than previously observed.

For Avastin® in combination with capecitabine, the Committee of the European Medicines Agency found that although the data showed a modest increase in progression-free survival, no clinically relevant effects were observed on other endpoints such as overall survival or health-related quality of life. The relatively modest benefits were considered not to outweigh the high toxicity of the combination of Avastin® and capecitabine, given that the new indication was aimed at patients for whom a relatively mild treatment would be appropriate. Therefore the Committee concluded that the new indication should not be approved. However, for Avastin® in combination with paclitaxel, the Committee concluded that the benefits continue to outweigh the risks, because the available data have convincingly shown to prolong progression-free survival of breast cancer patients without a negative effect on the overall survival. Therefore, the Committee therefore recommended that for the treatment of breast cancer Avastin® should only be used in combination with paclitaxel.

“After careful review of the clinical data, we are recommending that the breast cancer indication for Avastin® be removed based on evidence from four independent studies,” Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “Subsequent studies failed to confirm the benefit observed in the original trial. None of the studies demonstrated that patients receiving Avastin® lived longer and patients receiving Avastin® experienced a significant increase in serious side effects. The limited effects of Avastin® combined with the significant risks led us to this difficult decision. The results of these studies are disappointing. We encourage the company to conduct additional research to identify if there may be select groups of patients who might benefit from this drug.”

Removing the breast cancer indication from the Avastin® label will be a process, and a process that no doubt will be complicated by the fact that the European Medicines Agency determined that the available data convincingly shows prolonged progression-free survival of breast cancer patients without a negative effect on the overall survival. In any event, the recommendation of the FDA to remove the label indication from Avastin® is the first step, and the drug itself is not being removed from the market.

In a bit of a disingenuous statement, the FDA explained in a press release that the recommendation to remove the label indication will not have any immediate impact on its use in treating breast cancer. It would seem that the FDA is unfamiliar with the breed of species known as plaintiffs’ personal injury lawyers and the fact that many, if not most, doctors practice medicine in a way to be extremely conservative knowing that any time there is an adverse outcome there is the possibility of getting sued. With the announcement today that there are significant risks presented with using Avastin® it would seem likely that many doctors prescribing the drug to treat breast cancer will shy away from such treatment out of an abundance of caution. Of course, time will tell, and today’s recommendation should not affect the approvals for colon, kidney, brain, and lung cancers.

The agency has informed Genentech of its proposal to withdraw marketing approval of the drug for breast cancer. Genentech has not agreed to remove the breast cancer indication voluntarily, so the agency has issued a Notice of Opportunity for a Hearing, which permits Genentech to request a public hearing if it wishes to contest the agency’s determination. The company has 15 days to request a hearing; if it does not do so, the hearing will be waived, and FDA will begin proceedings to remove the breast cancer indication. Rest assured, Genentech will request a hearing.

“We are pleased that the EMA has confirmed the benefits of Avastin® with paclitaxel and that Avastin® will continue to be available for women with metastatic breast cancer living within the European Union with metastatic breast cancer,” said Hal Barron M.D., chief medical officer and head, Global Product Development. “We believe women living in the United States with metastatic HER2-negative breast cancer should also have Avastin® as a treatment option, and, therefore, we will request a hearing with the FDA.”

The Author

Gene Quinn

Gene Quinn is a Patent Attorney and Editor and President & CEO ofIPWatchdog, Inc.. Gene founded IPWatchdog.com in 1999. Gene is also a principal lecturer in the PLI Patent Bar Review Course and Of Counsel to the law firm of Berenato & White, LLC. Gene’s specialty is in the area of strategic patent consulting, patent application drafting and patent prosecution. He consults with attorneys facing peculiar procedural issues at the Patent Office, advises investors and executives on patent law changes and pending litigation matters, and works with start-up businesses throughout the United States and around the world, primarily dealing with software and computer related innovations. is admitted to practice law in New Hampshire, is a Registered Patent Attorney and is also admitted to practice before the United States Court of Appeals for the Federal Circuit. CLICK HERE to send Gene a message.

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