The FDA’s controversial decision to approve Biogen and Eisai’s Alzheimer’s disease treatment Aduhelm (aducanumab) has prompted a third member to resign from the advisory committee that had solidly voted down the drug during a consultation meeting last year. The departure of Aaron Kesselheim from the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee (AdCom) follows those of fellow panelists Joel Perlmutter and David Knopman who left in protest this week after the agency cleared the anti-amyloid antibody on Monday.
In a letter to FDA Acting Commissioner Janet Woodcock, Kesselheim called Monday’s ruling “probably the worst drug approval decision in recent US history,” and said the regulator “owes it to the nation to provide a detailed justification” for going against the advice of the panel.
The 11-member panel was convened by the FDA last November to discuss the Aduhelm application, and was asked to vote on several questions pertaining to the evidence of the drug’s effectiveness. Committee members were nearly unanimous in concluding that the clinical evidence did not support approval. However, the agency still cleared Aduhelm, using an accelerated pathway that had not been discussed at the meeting, on the basis that the drug can remove beta amyloid from the brain and that this was “reasonably likely to result in clinical benefit.”
FDA needs to re-think AdComs
In his resignation letter, Kesselheim wrote that during the November meeting, concerns about the data “were not given adequate time for discussion,” and the question of whether an Alzheimer’s drug should be approved based on the surrogate endpoint of amyloid lowering alone “was specifically excluded.” He also cited the FDA’s controversial decision to grant accelerated approval to Sarepta Therapeutics’ Duchenne muscular dystrophy treatment Exondys 51 (eteplirsen) in 2016 as another example of the regulator authorising a drug against the recommendations of its advisory committee.
Kesselheim said his rationale for leaving the panel “was that the FDA needs to re-evaluate how it solicits and uses the advisory committees…because I didn’t think that the firm recommendations from the committee in this case…were appropriately integrated into the decision-making process.”
Earlier this week, Knopman, a neurologist at Mayo Clinic, said he resigned because he was “very disappointed at how the advisory committee input was treated by the FDA,” while Perlmutter, a neurologist at Washington University, left “due to the FDA approval of [Aduhelm] without further discussion with the advisory panel,” according to a spokeswoman for the university.
June 10th, 2021