An OIG report zeroed in on what it said were three particularly problematic accelerated approvals: Biogen’s Aduhelm, Sarepta’s Exondys and Covis’ Makena.
The Office of the Inspector General at the Department of Health and Human Services raised concerns on Wednesday regarding what it characterized as lapses in the FDA’s judgement in granting accelerated approval to certain medications.
In a 32-page report, the Office of the Inspector General (OIG) flagged three drugs in particular—Biogen’s Alzheimer’s disease antibody Aduhelm (aducanumab), Sarepta’s Duchenne muscular dystrophy therapy Exondys (eteplirsen) and Covis Pharma’s Makena (hydroxyprogesterone caproate)—for which it said the accelerated approval process “deviated” from the appropriate pathway “in ways that raised concerns.”
The OIG identified three main avenues by which the FDA improperly granted accelerated approvals. For all three drugs, for instance, the regulator pushed through with accelerated approval “despite concerns from its own reviewers and/or advisory committees,” the report read. In addition, the FDA’s review for two of the three problematic drugs—Aduhelm and Exondys—involved data and analyses not included in the companies’ original plans.
Finally, for Aduhelm exclusively, the OIG’s investigation found that some meetings with the sponsoring drug companies were “missing” or otherwise “mentioned but not fully documented” in the regulator’s administrative files. “Although these meetings were documented as having happened, the lack of details regarding the meetings makes it difficult to determine whether the meetings contributed significantly to FDA’s decision making,” according to the report.
Both Makena and Aduhelm have been removed from the market. Biogen withdrew its Alzheimer’s therapy in January 2024 after a disappointing launch followed by months of Congressional inquiries. The FDA pulled its approval of Covis’ preterm birth drug Makena in April 2023, citing evidence that the drug had not been performing its intended purpose of improving neonatal outcomes.
Exondys is still commercial, though its confirmatory trial is delayed. “Eteplirsen was approved in 2016, but after 8 years its confirmatory trial had yet to provide evidence of clinical effectiveness,” the OIG report pointed out.
Wednesday’s OIG report comes as the FDA’s accelerated pathway recently came under increased scrutiny, prompted by a string of high-profile withdrawals and controversial approvals. The withdrawals included a handful of notable market exits such as Pfizer’s Oxbryta in September 2024 and Takeda’s Exkivity in October 2023. Among the controversial approvals was another Sarepta asset: the Duchenne muscular dystrophy gene therapy Elevidys.
In June 2023, the regulator granted Elevidys accelerated approval despite its missing its primary endpoint in a Phase I study. A year later, in June 2024, the FDA converted Elevidys’ accelerated approval into a full one, a decision that many considered to be questionable given that the gene therapy failed its confirmatory Phase III trial.
