During a listening session convened by the Friends of Cancer Research (FOCR) with Reps. Diana DeGette (D-CO) and Fred Upton (R-MI) on their nascent Cures 2.0 package, Richard Pazdur, director of the US Food and Drug Administration’s (FDA) Oncology Center of Excellence (OCE) defended the agency’s accelerated approval program.
(RELATED: Cures 2.0: Discussion draft signals impact on FDA, creation of ARPA-H, Regulatory Focus 23 June 2021)
Asked by DeGette whether FDA’s expedited pathways, such as accelerated approval and breakthrough therapy designation, are working as intended, Pazdur declared that the accelerated approval program is under attack by critics who misunderstand it.
“Do you think accelerated approval is under attack? I do. Do you think that some of the critics of accelerated approval may provide a one-sided viewpoint? I do,” Pazdur said.
Pazdur’s impassioned defense of the program comes amid backlash against the agency’s controversial decision to grant accelerated approval to Biogen’s Alzheimer’s drug Aduhelm (aducanumab) and follows recent moves by the agency to review “dangling” accelerated approvals of drugs that have failed to show clinical benefit.
(RELATED: Industry-wide accelerated approval review yields four withdrawals, Regulatory Focus 10 March 2021; ODAC recommends pulling 2 of 6 accelerated approvals, Regulatory Focus 30 April 2021; Woodcock calls for investigation into Aduhelm approval, Regulatory Focus 9 July 2021; FDA defends Aduhelm’s accelerated approval, while others call for reform, Regulatory Focus 14 July 2021)
“I’m not opposed to criticism … I think there is room for improvement, but we really have to take a look at a comprehensive viewpoint of the accelerated approval program,” Pazdur said, pointing to the 155-plus accelerated approvals granted for oncology indications since the program’s inception. Thus far, only about 10 of those indications have been removed from the market.
“If you only view things from one lens here, of the problems of the program, you miss the entire big picture of what has happened here in oncology,” Pazdur said, adding that accelerated approval has allowed some “very important” oncology drugs to enter the market years before their confirmatory studies were completed.
Much of the criticism of the program has focused on FDA’s oversight and enforcement of postmarketing requirements for products with accelerated approval. A recent analysis from The BMJ finds that of the 253 indications granted accelerated approval from 1992 to 2020, 112 have not had their clinical benefit confirmed, yet only 16 have been withdrawn.
However, Pazdur deflected some of the criticism, pointing out that the results of confirmatory trials are just part of the picture.
“A failed trial does not mean a failed drug,” he said, “There are many reasons why [one] can fail, the trial was not designed appropriately, it didn’t enroll enough patients, they selected the wrong patient population … they chose the wrong endpoint to look at.”
Pazdur also said he is convinced products granted accelerated approval are benefiting patients. Using the example of multiple myeloma, Pazdur noted that, “We’ve approved now 10 drugs and the average life expectancy for a common hematological malignancy is now anywhere between eight to 10 years, when prior it was about two years. That is greatly due to the drugs that were approved under accelerated approval. Most of them, if not all of them, were approved on response rate or time to progression, not on overall survival.”
Pazdur did present several suggestions for how to improve the accelerated approval program.
“Can we improve this program? … I think yes, we can. Some of the difficulties, such as removing drugs from the market when they don’t meet their primary endpoint or when we believe the standards of medicine have changed,” could be addressed.
Another suggestion Pazdur made would be to have discussions with companies to develop comprehensive drug development plans for products that will go through the accelerated approval pathway, “Really looking at what are the confirmatory studies and the accelerated approval studies, before the drug is even filed.”