A prominent Harvard Medical School professor has resigned from a U.S. Food and Drug Administration advisory panel in protest over the agency’s decision to approve Biogen Inc.’s Alzheimer’s drug Aduhelm.
The doctor, Aaron Kesselheim, announced his departure in a letter to FDA Acting Commissioner Janet Woodcock. He is the third committee member to quit in the wake of the highly controversial approval.
The clearance “was probably the worst drug approval decision in recent U.S. history,” Kesselheim said in the letter.
Evidence that the drug works is mixed. Two big clinical trials produced conflicting results on whether it could slow cognitive decline, leading the advisory panel Kesselheim served on to urge the FDA not to let it on the market without further study.
The agency elected to give the treatment a conditional approval on the basis that it could remove a bad protein called amyloid from the brain. Biogen must conduct an additional trial to confirm the drug’s effectiveness, the FDA said.
The drug’s clearance was celebrated as a landmark by Alzheimer’s patients and many doctors. It was the first therapy for the brain-wasting disease to be approved in roughly two decades, and it is likely to be a blockbuster for Biogen and its partner, Tokyo-based Eisai Co.
At a meeting in November, the advisory panel voted 8 to 1, with 2 undecided, that data from a single clinical trial with positive results was insufficient to show Biogen’s drug works. They also voted 10 to 0, with 1 undecided, that the positive study shouldn’t be considered primary proof the drug works in light of conflicting evidence from a different trial.
“The agency owes it to the nation to provide a detailed justification” for going against the advice of the panel, Kesselheim said.
“FDA considered the committee’s input, weighed the overall evidence in the application, and considered the dire situation of patients with AD who have few treatment options,” an agency spokeswoman said in an email. “Based upon this, the FDA concluded that an accelerated approval was appropriate.”
The agency doesn’t comment on matters related to individual advisory committee members, she said.
During the November advisory committee meeting, concerns about the data “were not given adequate time for discussion” and the crucial question of whether an Alzheimer’s drug should be approved based on amyloid lowering alone “was specifically excluded from discussion,” Kesselheim wrote.
The doctor also made broader criticisms of the agency, saying it needed to reassess its decision-making process.
Kesselheim is the third member to quit the committee, following Joel Perlmutter from the Washington University School of Medicine and David Knopman from the Mayo Clinic. Both Perlmutter and Kesselheim voted against the drug, while Knopman was recused from the November hearing as he had already staked out a public position critical of the trial results.
Perlmutter resigned “due to the FDA approval of aducanumab without further discussion with the advisory panel,” a spokeswoman for Washington University said in an email.
“I am extraordinarily disappointed that our unbiased advisory committee review was not valued,” Perlmutter said in an email. Approving a drug that may not be effective “has serious potential to impair future research into new treatments.”
Knopman’s resignation was confirmed by the Mayo Clinic.