By Kevin E. Noonan --
It has been a difficult year for Genentech with regard to its blockbuster anticancer drug, Avastin® (bevacizumab). For much of the year, the company was embroiled in a dispute with the ophthalmological community over its decision (now altered) to limit sale of Avastin® for reformulation in treating age-related macular degeneration (AMD) in favor of Lucentis®, a related (and much more expensive) formulation of a Fab fragment of the same monoclonal antibody drug but having the advantage of FDA approval for AMD treatment (see links below). Then, just last December, the FDA's Oncology Drug Advisory Committee voted 5-4 to recommend Avastin® not be approved for treating metastatic breast cancer. The basis for the decision was the absence of a clinical trial of 722 women with metastatic breast cancer, where patients receiving a combination of Avastin® and paclitaxel showed lack of tumor growth for 11.8 months, compared with 5.8 months in patients receiving paclitaxel alone. However, there was no improvement in overall survival (26.5 months versus 24.8 months), and patients receiving Avastin® suffered significant side effects, including high blood pressure, blood clots, heart problems, bowel perforation, and evidence of kidney damage. These results were in contrast with results obtained for Avastin® treatment for lung and colon cancer, where significant overall survival times were improved. They were, however, consistent with an earlier study showing no improved survival times for breast cancer patients treated with the combination of Avastin® and another anticancer drug, capecitabine.
On Friday, the FDA took the unusual step of rejecting the Advisory Panel's recommendation and approving Avastin® for breast cancer treatment in combination with other anticancer drugs like paclitaxel. Moreover, it granted accelerated approval to this indication of the drug, which is intended "to make promising products for life-threatening diseases available on the market on the basis of preliminary evidence prior to formal demonstration of patient benefit," according to the FDA's website. Approval is important, as it is estimated to increase Genentech's already healthy Avastin® sales figures ($2.3 billion in 2007) by almost half a million dollars per year. FDA approval triggers both insurance reimbursement for the treatment and a commitment from Genentech that the cost of treatment will be capped at $55,000 per year (it can cost as much as $100,000 per year without the cap). It is also expected to increase the number of metastatic breast cancer patients getting Avastin® combination therapy from the approximately 9,500 patients currently getting "off-label" treatment.
The decision raises questions of how the FDA will address approval standards for late-stage cancer treatments. According to Dr. Kay Dickerson of the Center for Clinical Trials at Johns Hopkins University, "[i]f FDA sets a precedent of approving a drug based on progression free survival, people are afraid they may stop looking at survival as the most important endpoint." The decision also suggests an acceptance at the FDA of principles advocated by academic critics (and supporters) of the FDA, such as Professor Richard Epstein at the University of Chicago Law School (see "Overdose: How Excessive Government Regulation Stifles Pharmaceutical Innovation"), that the FDA should permit patients to make the judgment of whether to use drugs like Avastin® for terminal diseases. However, those espousing such "free market" solutions neglect to consider whether decisions like the FDA's approval of Avastin® represents an abdication of the agency's responsibility to make scientifically-reasoned, dispassionate assessments of drug efficacy for individuals in the throes of deadly diseases, whose capacity for dispassion may be compromised. While certainly the case that the drug can give patients hope (a sentiment expressed by Margaret C. Kirk, Executive Director of the Y-ME National Breast Cancer Organization), whether this is enough to determine approval as a consistent policy is an important question the FDA has yet to adequately address.
For additional information regarding this and other related topics, please see:
• "Compromise Resolves Avastin® Dispute," December 26, 2007
• "Genentech Beset with Avastin® Woes," December 6, 2007
• "Age-related Macular Degeneration Patients Get a (Limited) Reprieve," November 7, 2007
• "Genentech Acts to Halt Off-label Use of Avastin® for Age-related Macular Degeneration," October 21, 2007
• "Genentech CEO Defends Differential Cost for Avastin®/Lucentis® Treatment of Macular Degeneration," June 6, 2007
• "Retinal Specialist on the Avastin®/Lucentis® Controversy," February 23, 2007
• "Lower Doses of Genentech's Avastin® Effective in Treating Lung Cancer," February 23, 2007
Comments