Fallout continues from the Food and Drug Administration’s controversial decision this week to approve Biogen̵
Three experts who sat on an advisory committee of the FDA have now withdrawn over the decision.
The advisory committee reviewed the data behind Aduhelm last November and voted overwhelmingly against approval. Of the 11 advisers on the committee, 10 voted no on the question of whether Biogen had collected sufficient evidence to indicate that the substance is effective. The remaining adviser voted “unsure.”
Nevertheless, the FDA approved the drug on Monday. Although the regulator acknowledged that there is “residual uncertainty with regard to [the] clinical benefit ”by Aduhelm, the FDA said it decided to lower the approval requirements after the advisory committee had voted. Instead of basing the authorization on the proven efficacy of the drug, the agency relied on a “surrogate endpoint.” In this case, the surrogate is the drug’s ability to reduce amyloid beta plaques in the brain of some Alzheimer’s patients.
“This reduction in plaques is likely to result in clinical benefit,” Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research, wrote in a statement this week.
The approval and explanation went to advisory committee member Aaron Kesselheim, a professor at Harvard Medical School who is also the director of the regulation, therapy and law program at Brigham and Women’s Hospital. In a burning resignation letter sent to FDA Commissioner Janet Woodcock on Thursday, Kesselheim called the FDA’s decision “probably the worst decision on drug approval in recent U.S. history.”
He noted that the surrogate endpoint was not discussed by the advisory committee – in fact, he notes that the FDA specifically told the committee that it would not use amyloid beta-plaque clearing as a surrogate for effectiveness.
Kesselheim also criticized other aspects of how the FDA monitored the committee meeting, writing:
At our public meeting, concerns about trial data from one of the FDA’s own reviewers were not given sufficient time for discussion, and some of the questions the FDA asked the committee to answer were worded in a way that seemed oblique to answer. that would favor drug approval.
Overall, he described the decision as a debacle and wrote that “it is clear to me that the FDA is not currently able to adequately integrate the committee’s scientific recommendations into its approval decisions.” As such, he stepped down from the selection he had served since 2015.
Upon resignation, he joins neurologists David Knopman of the Mayo Clinic in Minnesota and Joel Perlmutter of Washington University in St. Louis. Louis, who both also announced their resignations this week.
As for the remaining questions about the efficacy of Biogen’s Aduhelm, the FDA required that Biogen conduct another clinical trial to evaluate the efficacy of the drug. If the company does not state that the drug is effective, the FDA may revoke the approval. However, Biogen has up to nine years to submit its data. During this time, the drug can be prescribed to patients – at a list price of $ 56,000.
In an interview with Axios published on Friday, Biogen’s chief physician Maha Radhakrishnan responded to the question of why the company had not just started further trials already given the clear uncertainty in the data seen since 2019. Radhakrishnan said that the FDA did not ask the company to do so to get approval.