Six companies were brought before a panel of Food and Drug Administration (FDA) advisers today to explain why they had not yet completed post-marketing studies required under the agency’s accelerated approval program.
The presentations were part of a day-long discussion of the program as it has applied to cancer drugs. Accelerated approval, intended to speed new treatments to patients who have few options left, is sometimes criticized for rushing drugs to market without sufficient evidence of their efficacy.
Full approval of accelerated drugs is conditional upon the completion of additional studies mandated by the FDA. Today, the FDA said that about 10% of oncology accelerated approvals eventually fail in these subsequent trials, but argued that this is the trade-off needed to bring promising drugs for severe and life-threatening diseases to patients quickly.
On 16 December last year, the FDA proposed stripping the breast cancer indication from Avastin (bevacizumab), saying that studies had failed to confirm a significant benefit of the drug. It was the first time that the agency proposed to remove an accelerated approval indication. Avastin had been approved for breast cancer for just under three years before the FDA made the controversial decision. The drug’s manufacturer, Genentech, has appealed the decision.
Paul Kluetz, a medical officer in the FDA’s Division of Drug Oncology Products noted today that of the 49 indications for 37 cancer products approved under the accelerated program, 55% have completed post-marketing surveillance studies verifying benefit and 10.2% of the drugs failed in post-marketing studies.
That leaves many that have not yet completed their post-marketing requirements. Five drugs had not completed the required testing in over five years since receiving accelerated approval. “While FDA is pleased with the success of the accelerated approval program in providing more access to oncology drugs, the importance of decreasing the time that potentially ineffective therapies are on the market cannot be overstated,” said Kluetz.
For their part, the companies presenting today cited several problems in completing their obligations. Eli Lilly (based in Indianapolis, Indiana) and Amgen (headquartered in Thousand Oaks, California) both learned that their colorectal cancer drugs – Erbitux (cetuximab, approved in 2004) and Vectibix (panitumumab, approved in 2006), respectively – were less effective in cancers that contain certain mutations. This meant the companies needed to change their trials to incorporate genetic screening – a particularly difficult task, the representative from Amgen noted, if there is no FDA-approved test for the mutations.
Amgen said it has also struggled with changes in the standard-of-care guidelines in the United States. Amgen’s drug Vectibix inhibits a protein called EGFR. When anti-EGFR drugs were added to the standard-of-care regime, conducting the trial as Amgen had designed it would have required withholding standard care from some patients. Instead, Amgen had to move its study to countries where anti-EGFR drugs are not standard-of-care.
After the company presentations, FDA advisers discussed tightening requirements for the accelerated approval program. Some were in favor of adding additional clinical trial requirements, and requiring companies to begin confirmatory clinical trials before receiving accelerated approval.
Several panelists expressed unease with what they said were low standards for the program: “I want to make sure we don’t get into the business of lowering the bar in the name of compassion,” said one.
Correction: an earlier version of this post stated that the FDA had removed the breast cancer indication for Avastin. In fact, the FDA has proposed to remove the indication, but that decision is not yet final.