A third member of a Food and Drug Administration expert panel has resigned over the agency’s contentious approval of an Alzheimer’s therapy this week, a sign of a growing backlash over the decision.
In a letter to acting FDA Commissioner Janet Woodcock on Thursday, Aaron Kesselheim, who had served on the FDA’s advisory committee for nervous system therapies since 2015, wrote that the approval of Biogen’s Aduhelm “was probably the worst drug approval decision in recent U.S. history.”
“It is clear to me that FDA is not presently capable of adequately integrating the Committee’s scientific recommendations into its approval decisions,” wrote Kesselheim, the director of Brigham and Women’s Hospital’s Program on Regulation, Therapeutics, and Law. He also cited the FDA’s decision to approve Sarepta Therapeutics’ eteplirsen for Duchenne muscular dystrophy in 2016 over the recommendation of the advisory committee in his decision to quit.
Kesselheim’s resignation follows those of neurologist David Knopman of the Mayo Clinic and neurologist Joel Perlmutter of Washington University in St. Louis. Perlmutter wrote in an email to STAT Tuesday his decision to quit the panel was “due to this ruling by the FDA without further discussion with our advisory committee.”
Knopman, whose resignation was first reported Wednesday by Business Insider, was recused from the aducanumab panel because he had been a trial investigator.
But during the panel’s November hearing on the therapy, 10 of the 11 members voted that there was not enough evidence to show Aduhelm, also known as aducanumab, could slow cognitive decline, recommending against its approval. The 11th voted “uncertain.”
On Monday, however, the FDA granted Aduhelm an accelerated approval based on the drug’s ability to clear toxic protein plaques in patients’ brains — a regulatory route that FDA officials told the advisory committee in November was not being considered. In explaining the approval, the FDA acknowledged Aduhelm had not demonstrated a clear clinical benefit in terms of slowing disease progression, but argued that by removing the plaques, Aduhelm “is reasonably likely to predict a clinical benefit to patients.”
The FDA also told the chair of the panel Monday that “further discussions” within the agency after the panel’s hearing led to the decision to use the accelerated approval pathway.
The FDA does not have to follow the recommendations of its advisory committees, and researchers have found that it has gone against the votes about 1 in 5 times in recent years. But generally, such overrulings occur when the votes are much closer.
Nicholas Florko contributed reporting.
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