Inspector General Report Flags FDA's Accelerated Approvals of Aduhelm, Exondys, and Makena
Key Insights
An Inspector General report has raised concerns about the FDA's accelerated approval process for certain drugs, citing deviations from appropriate pathways.
The report specifically highlights Biogen's Aduhelm, Sarepta (search)'s Exondys, and Covis Pharma (search)'s Makena as examples where the FDA's judgment is questioned.
Issues identified include approvals despite internal reviewer concerns, use of data not in original plans, and inadequate documentation of meetings with sponsors.
The FDA's accelerated approval pathway is under scrutiny following a report from the Department of Health and Human Services' Office of the Inspector General (OIG), which identified lapses in the agency's judgment when granting accelerated approval to certain medications. The OIG's 32-page report specifically called out Biogen’s Aduhelm (aducanumab), Sarepta (search)’s Exondys (eteplirsen), and Covis Pharma (search)’s Makena (hydroxyprogesterone caproate), stating that the accelerated approval process "deviated" from the appropriate pathway in ways that raised concerns.
The OIG's investigation highlighted three main issues. First, for all three drugs, the FDA proceeded with accelerated approval despite reservations from its own reviewers and/or advisory committees. Second, the review processes for Aduhelm and Exondys involved data and analyses that were not part of the companies' original plans. Finally, the OIG found that for Aduhelm, some meetings with the sponsoring drug companies were either missing or not fully documented in the FDA's administrative files, making it difficult to determine their impact on the FDA's decision-making.
Market Withdrawals and Delayed Confirmatory Trials
Notably, both Makena and Aduhelm have since been removed from the market. Biogen withdrew Aduhelm, an antibody therapy for Alzheimer's disease, in January 2024 after a disappointing launch and Congressional inquiries. The FDA pulled its approval of Covis’ Makena, a drug intended to prevent preterm birth, in April 2023, based on evidence that it did not improve neonatal outcomes. Sarepta (search)'s Exondys, approved in 2016 for Duchenne muscular dystrophy (search), remains on the market, but its confirmatory trial has been delayed, with the OIG report noting that after eight years, the trial had yet to provide evidence of clinical effectiveness.
Increased Scrutiny of Accelerated Approvals
The OIG report arrives amidst growing scrutiny of the FDA's accelerated approval pathway, triggered by a series of high-profile withdrawals and controversial approvals. Recent market exits include Pfizer’s Oxbryta in September 2024 and Takeda’s Exkivity in October 2023. Another Sarepta (search) asset, the Duchenne muscular dystrophy (search) gene therapy Elevidys, also faced controversy. In June 2023, Elevidys received accelerated approval despite missing its primary endpoint in a Phase I study. A year later, in June 2024, the FDA converted Elevidys’ accelerated approval into a full approval, a decision that was met with skepticism given the gene therapy's failure in its confirmatory Phase III trial.