FDA AdCom roster shrinks as two quit over Aduhelm approval

Mayo Clinic neurologist David Knopman on Wednesday became the second member of the FDA's Peripheral and Central Nervous System Drugs Advisory Committee (AdCom) to resign in protest at the agency's decision earlier this week to approve Biogen and Eisai's Alzheimer's disease drug Aduhelm (aducanumab).

The 11-member panel was nearly unanimous last November in concluding that the clinical evidence did not support approval of the anti-amyloid antibody. On Tuesday, Washington University neurologist Joel Perlmutter, a member of the advisory group who had voted against the drug at the meeting, resigned from the committee as well, citing the FDA's decision to authorise Aduhelm without further discussion with its advisors.

In its approval announcement on Monday, the FDA said it cleared Aduhelm using an accelerated approval pathway that had not been discussed at the November AdCom meeting. The agency, which usually follows the advisory panel's recommendations, but is not obligated to, explained that its decision was based on a surrogate endpoint; namely, the drug's ability to eliminate beta-amyloid, which it said was "reasonably likely to result in clinical benefit." Billy Dunn, director of the agency's Office of Neuroscience, wrote in a letter to AdCom chairman Nathan Fountain after the approval announcement that the panel's input from the November meeting prompted further discussions at the FDA that ultimately led to the decision to use the accelerated pathway.

Advisory panel was 'not well-treated'

Knopman did not participate in the AdCom vote in November, having been recused over a conflict of interest because he was an investigator on clinical trials of the drug (see ViewPoints: Inauspicious start to a big week for Biogen's aducanumab). However, he stated Wednesday that while he "[recognises] that the role is advisory…I felt that the advisory committee in this situation was not well-treated, and I think that I just don't choose to put myself into that position in the future for the FDA." The FDA declined to comment on the resignations, saying the agency does not discuss matters related to individual members of advisory committees.

Meanwhile, Knopman said he would still offer Aduhelm to his patients when it becomes available, describing that as a "completely separate issue." The neurologist said that since the drug was approved by the FDA and would be commercially available, "I feel ethically bound to offer the treatment…I will present [patients] with my side of the story, and with the FDA's side of the story" that reducing amyloid may offer a clinical benefit in the future.

For more, see Physician Views Results: Alzheimer's docs split on whether the FDA was right to approve Aduhelm.

To read more Top Story articles, click here.