A government watchdog examining the FDA’s accelerated approval pathway has released a 32-page report (PDF) that concludes the agency’s controversial endorsement of Biogen’s failed Alzheimer’s treatment Aduhelm was generally an outlier.
In reviewing 24 accelerated FDA approvals, the Department of Health and Human Services (HHS) Office of Inspector General (OIG) uncovered issues with just two other nods: those for Sarepta Therapeutics' Duchenne muscular dystrophy (DMD) therapy Exondys and for Covis Pharma’s preterm birth drug Makena.
The OIG found that the FDA approved all three drugs despite concerns raised by its own reviewers or independent advisory committees. In two of the approvals, the FDA used analyses that were not included in the sponsor’s original plan. The OIG also discovered a lack of documentation of some meetings between sponsors and the FDA.
In its report, the OIG made two recommendations to “strengthen guardrails” that it said would “ensure appropriate and consistent use of the accelerated approval pathway.”
According to the report, the FDA agreed with the inspector that it should ensure that all meetings are completely documented and included in administrative files. But it did not concur with the OIG’s other suggestion that it should define specific factors that would require the FDA’s accelerated approval council to advise on certain drug applications.
“The accelerated approval council consists of senior leaders from multiple centers, CDER, CBER, and OCE,” the FDA wrote in its response. “Involving leaders from other centers in a wide array of cases could waste scarce agency resources because they would need to spend considerable resources to evaluate a specific drug application before another center.”
The FDA established its accelerated approval program in 1992 to allow drugs to reach the market quickly for life-threatening conditions for which there is no alternative treatment. The approval then is contingent upon a confirmatory trial. But the FDA has had difficulty enforcing its post-marketing requirements.
For example, Sarepta has yet to complete its confirmatory trial for Exondys, which was approved in 2016. Last year, the FDA granted an accelerated approval to Sarepta’s gene therapy Elevydis after an advisory panel gave it a thumbs up by an 8-6 vote.
As for Covis’ Makena, which was approved in 2011, the FDA pulled back its nod two years ago after a failed confirmatory trial in 2019 and two advisory committee meetings.
Additionally, the report pointed out that Exondys and Aduhelm were approved after the FDA weighed trial data that were not included in the companies’ original application.
Aduhelm was approved in 2021 after an advisory committee voted overwhelmingly to recommend that it be rejected. The decision prompted three members of the panel to quit. Early last year, Biogen pulled the plug on the treatment.