ROCHESTER, Minn. — A Mayo neurologist who recently quit an FDA expert panel in protest has been joined by two others asserting the agency erred in going against experts to approve a new drug for Alzheimer's disease.
In leaving the FDA's Peripheral and Central Nervous System Advisory Committee last week, Mayo Clinic neurologist Dr. David Knopman was joined by Dr. Joel S. Perlmutter, a neurologist at Washington University in St. Louis, and Harvard Medical School ethicist Dr. Aaron Kesselheim.
Knopman was a site investigator for one of two major studies of aducanumab, the first treatment meant to fight Alzheimer's by targeting brain amyloid, a plaque associated with the disease. The drug, manufactured by Biogen for sale as Aduhelm, is effective at reducing amyloid plaque but has only weak data supporting its benefits in reducing cognitive symptoms, according to critics.
As a member of the expert panel and a trial investigator who helped to study the drug, Knopman did not take part in the panel's deliberations when it voted overwhelmingly to reject aducanumab in December. He did publish a paper suggesting the need for more study.
A statistician who advised the panel compared the evidence in support of the drug to shooting a rifle at a barn, "then painting a target around the bullet holes."
Faced with such opposition from reviewers, the FDA usually declines to approve drugs for sale. Instead the agency last week granted the treatment's conditional approval. The news elicited cheers among Alzheimer's patient groups and sent Biogen's stock soaring. The drugmaker plans to charge $56,000 annually for the drug, which will largely be funded by Medicare.
In a resignation email to the FDA that Kopman shared with The Washington Post, the physician wrote that “the approval of aducanumab … made a mockery of the [advisory] committee’s consultative process," adding that FDA staff had asked "biased questions" of the panel, and that the approval "appears [to] have been foreordained.”
Contacted for permission to ask Knopman to elaborate, Mayo Clinic Communications Manager Kevin Punsky offered the following: "David Knopman, M.D., has resigned from the FDA's Peripheral and Central Nervous System Advisory Committee. He was honored to serve on the committee. Despite his disagreement with the FDA's decision to approve the Alzheimer's drug aducanumab, he believes the FDA advisory committees provide valuable input to the FDA and the public."
Acting FDA chief in spotlight
The aducanumab approval has cast a spotlight on the administrator currently at the helm of the FDA, interim commissioner Dr. Janet Woodcock, an agency veteran during previous actions to approve drugs against expert opinion.
As a longtime head of the FDA's Center for Drug Evaluation and Research, Woodcock has come under fire this year from drug safety groups for her oversight as the opioid epidemic ravaged the nation.
A March letter by the patient advocacy group Breast Cancer Action opposed her potential nomination to lead the agency by asserting that Woodcock "is well-known for relaxing the criteria needed for certain drugs to reach the market ...."
In a January letter, 28 anti-opioid organizations cited Woodcock's oversight in "approving Zohydro despite a vote of 11-2 against approval by a scientific advisory committee," a 2018 move ushering an ultra potent painkiller to market in a period of widespread addiction.
Joining Knopman with his own resignation letter, Harvard's Kesselheim cited the agency's 2016 decision to approve a muscular dystrophy drug called eteplirsen, another approval which experts had rejected.
Though the panel has now shrunk by one-third, as of Tuesday, June 15, the three departed experts are still listed on the FDA webpage for the PCNS panel.