Drug companies need to “step up and take their drugs off the market as rapidly as possible” if a follow-up study shows their fast-tracked product doesn’t work, FDA’s oncology chief said.
Richard Pazdur, director of the Food and Drug Administration’s Oncology Center of Excellence, made his remarks in addressing criticisms of the accelerated approval program, which has come under fire after the agency’s controversial approval of Biogen’s Alzheimer’s drug Aduhelm. He has long supported ways to speed up access to potentially lifesaving medicines but acknowledged the need for changes to the program.
“This is a topic that’s near and dear to my heart since oncology is really the best user of accelerated approval,” he said Thursday at the Friends of Cancer Research annual meeting. “Most accelerated approvals are in our space.”
Pazdur’s comments come as Congress is deliberating whether to include FDA policy reforms in a year-end spending package, including House-passed changes to the accelerated approval program. The oncology chief and his colleagues published a New England Journal of Medicine perspective last month that called for a comprehensive strategy for accelerated approval in oncology.
Accelerated approval allows companies to bring their drugs to the market based on laboratory markers that predict a clinical benefit for patients, but don’t prove it outright. In exchange, drug companies agree to conduct postmarket studies to confirm whether the drug actually works.
Many companies do indeed pull their drug off the market if the confirmatory trial fails, Pazdur said. “But we do get into problems, as you know, with companies that are unwilling to do so.”
He made his remarks about a month after a scientific advisory panel recommended withdrawal of Covis Pharma’s preterm birth drug Makena. But that recommendation came two years after agency scientists called for removing the drug and more than a decade after the FDA allowed the drug on the market under the accelerated approval mechanism.
The FDA also withdrew an indication for Genentech’s Avastin. It’s approved to treat lung cancer, but the FDA pulled it as an advanced breast cancer treatment in 2011. The agency had approved it under the accelerated mechanism three years earlier.
The Avastin and Makena cases “represent challenges of how to make the system more nimble because a tremendous amount of the resources have gone into these hearings to remove a drug,” Pazdur said.
“It’s been 10 years, I think, since the Avastin hearing and it still is a nightmare for me what we went through,” he said. The hearing consumed many hours of preparation both for the company and the FDA “for very, very little reward.”
The FDA also wants companies to have a comprehensive plan for conducting confirmatory trials early in the drug development process, which Pazdur described as “the major thing that we’re really interested in.”
Larger pharmaceutical companies generally adhere to this and may have multiple postmarket studies, he said.
But “we do get into trouble” with a company that may not have adequate capital and wants to get their foot in the door by approving the drug based on a limited number of patients in a single-arm study, which means everyone enrolled received the same treatment.
“That puts the patient at risk here,” Pazdur said. “There is a period of vulnerability that we have to control and that period of vulnerability is between the time of the accelerated approval—if it is granted—and the confirmation or lack of confirmation of a clinical benefit in the confirmatory study. And we should try to reduce that period of vulnerability as much as possible.”