Federal Watchdog Calls for Improvements in FDA's Accelerated Approval Process
A federal watchdog has recommended changes to the Food and Drug Administration's (FDA) accelerated approval pathway, citing concerns over the agency's handling of certain high-profile drug approvals. The report, issued by the Department of Health and Human Services (HHS) Office of Inspector General (OIG), examined 24 FDA reviews that led to accelerated approvals and identified issues with three cases, including the controversial approval of Biogen's Alzheimer's drug Aduhelm.
Key Findings and Recommendations
The OIG's 32-page report highlighted several areas of concern in the FDA's accelerated approval process. In reviewing the 24 approvals, the watchdog found that the FDA approved three drugs despite concerns raised by its own reviewers or independent advisory committees. These cases included Biogen's Aduhelm, Sarepta Therapeutics' Duchenne muscular dystrophy (DMD) therapy Exondys, and Covis Pharma's preterm birth drug Makena.
The report made two primary recommendations to strengthen the accelerated approval pathway:
- Ensure complete documentation of all meetings with drug sponsors in administrative files.
- Define specific factors that would require the FDA's accelerated approval council to advise on certain drug applications.
While the FDA agreed with the first recommendation and has already taken steps to improve its documentation procedures, the agency disagreed with the second suggestion. The FDA argued that involving leaders from multiple centers in a wide array of cases could waste scarce agency resources.
Controversial Approvals and Their Aftermath
The report's findings shed light on the behind-the-scenes actions surrounding several controversial drug approvals:
Aduhelm (Biogen)
Approved in 2021 for Alzheimer's disease, Aduhelm's approval process was marked by unorthodox practices at the FDA. The decision prompted three members of the advisory panel to resign. Biogen ultimately pulled the drug from the market in 2024.
Exondys 51 (Sarepta Therapeutics)
Approved in 2016 for DMD, Exondys 51's approval involved a dispute between high-ranking FDA officials. The director of the FDA's drug division overruled the review team's decision not to approve the drug, leading to intervention by the FDA commissioner. The required confirmatory trial to demonstrate clinical benefit has been delayed.
Makena (Covis Pharma)
Approved in 2011 to reduce the risk of preterm birth, Makena's accelerated approval was withdrawn by the FDA in 2023 following a failed confirmatory trial in 2019 and two advisory committee meetings.
The OIG report noted that both Aduhelm and Makena are no longer on the market, while Exondys 51 remains available despite delays in its confirmatory trial.
Implications for the Pharmaceutical Industry
The findings of this report have significant implications for the pharmaceutical industry and the drug approval process. The accelerated approval pathway, established in 1992, allows drugs to reach the market quickly for life-threatening conditions with no alternative treatments. However, the FDA has faced challenges in enforcing post-marketing requirements and ensuring the completion of confirmatory trials.
As the industry and regulators grapple with these issues, the OIG's recommendations aim to strike a balance between expediting access to potentially life-saving treatments and maintaining the integrity of the drug approval process. The outcome of these proposed changes could shape the future landscape of drug development and approval in the United States.
References
- Government watchdog recommends tweaks to FDA accelerated approval program
A government watchdog examining the FDA’s accelerated approval pathway has released a report concluding that the agency’s controversial endorsement of Biogen’s failed Alzheimer’s treatment Aduhelm was generally an outlier. But the OIG also suggested tweaks to the approval program.
- Federal watchdog cites concerns with FDA’s accelerated approval process
The review, which was spurred by controversy over the FDA's Aduhelm approval, recommends two main changes in agency procedures.
Explore Further
How might the FDA's disagreement with the second recommendation in the OIG report affect future accelerated drug approvals?
What specific factors could be defined to require the FDA's accelerated approval council to advise on drug applications?
How has the pharmaceutical industry responded to the challenges highlighted in the OIG report regarding post-marketing requirements and confirmatory trials?
What are the potential risks and benefits of allowing drugs like Exondys 51 to remain on the market despite delays in confirmatory trials?
How can the FDA balance the need for expedited drug approvals for life-threatening conditions with the integrity and safety of the drug approval process?