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Inside Health Policy – Temple Says Cancer Drug Approvals Strong Despite Recent Criticisms

Inside Health Policy – Temple Says Cancer Drug Approvals Strong Despite Recent Criticisms


A top FDA drug center official refuted the idea that the number of oncology drugs going through accelerated approval is on the decline,

as industry and patient groups have recently asserted. Deputy drug center director Bob Temple said the agency has not become more reluctant to accept historical control trials and the overall number of oncology drug approvals is not declining — problems raised by lawmakers in questions to FDA officials at recent congressional hearings.

At a House user fee hearing earlier this month, FDA drug center Director Janet Woodcock responded to lawmaker questions about whether the agency was limiting the use of the accelerated approval pathway for cancer drugs. She said there has been disagreement between FDA and industry about response rates for historical control trials, which compare the response of patients using a new drug to a standard therapy. Response rates as low as 5 percent or 10 percent cannot show enough evidence for approval even though product sponsors have made that assertion, she said.

Members of industry have said there was a growing perception that FDA had become more reluctant to use accelerated approval for oncology drugs and that it is narrowing the use of single-arm studies .

Temple told FDA Week the agency still accepts such studies, but the evidence does not give a full sense of the drug’s capability and in the past historical controls were the the basis of approval for more severe diseases like leukemia.

“You’d make the leukemia go away for months, so there was little doubt that was beneficial,” he said. “But when you have a short term effect and only in a few percent, there’s going to be a discussion of whether that’s valuable.”

He agreed that low response rates cause concern about whether there is a real benefit to the drug. “I don’t believe we’ve ever approved a drug based on a 5 percent response rate,” he said. “I’d be very surprised to see that unless there were very dramatic responses in a rare disease then you could find out who were the responders. There might be a genetic basis for that, then it could be approved. But I don’t think this represents a change from the past.” Further he said the agency approved at least seven oncology drugs in 2011 and three in January.

But there has been indication that FDA could be considering making changes to its approach to oncology drugs, with a drug industry source citing the findings of an advisory committee last year. In February 2011, the oncologic drug advisory committee said it was considering alternatives to single arm trials — studies without a randomized control group — in refractory populations where no available therapy exists, despite the fact that those trials required less resources and time to complete.

The committee cited increasing difficulties in identifying and documenting a refractory population and marginal response rates in single arm trials and said alternatives to single arm trials could include randomized trials in a less refractory population against an active control and using a surrogate endpoint analyzed at an earlier time or a randomized trial in a refractory population comparing the investigational agent to best supportive care or various agents selected by investigators.

However, a cancer research advocate said there has been no evidence that the agency is using single arm trials less often. “I wouldn’t say that the agency is trending away from single arm trials,” said Jeff Allen, executive director of Friends of Cancer Research. He said many industry stakeholders have questioned whether FDA is still allowing them as often as it has in previous years but that he has not seen any significant changes in FDA’s position on oncology drug approval process since randomized trials have long been the “gold standard” of trials. Allen has pegged declines in oncology accelerated approvals on sponsor endpoint choices and industry perceptions that the agency is becoming more conservative about the use of surrogate endpoints.

Friends of Cancer Research is backing a recently introduced bill that would create a breakthrough drug designation to expedite development of drugs that show effectiveness early (see related story). FDA officials have voiced support for the idea, saying they would like to use adaptive clinical trial designs and collaborate with drug sponsors to push promising drugs through the pipeline.