WASHINGTON — Two members of a Food and Drug Administration advisory panel resigned this week after the agency’s contentious decision to approve an Alzheimer’s drug over the objections of its outside advisers.
David Knopman, a neurologist at the Mayo Clinic, said Wednesday in an e-mail to The Washington Post that he did not “wish to be part of a sham process” that ultimately resulted in the agency’s approval Monday of Biogen’s Aduhelm, also known as aducanumab.
He also shared the e-mail he sent to FDA officials saying that he was resigning immediately. He told the officials: “The whole saga of the approval of aducanumab . . . made a mockery of the [advisory] committee’s consultative process. While I realize that the committee is advisory, the approval of aducanumab appears [to] have been foreordained.”
Earlier this week, Joel Perlmutter, a neurologist at Washington University in St. Louis, resigned from the committee, according to the trade publications Stat News and the Pink Sheet. Perlmutter told Stat in an e-mail that he quit “due to this ruling by the FDA without further discussion with our advisory committee.”
The FDA declined to comment on the resignations, saying the agency does not talk about matters related to individual members of advisory committees.
The FDA decision to approve Aduhelm set off a firestorm because critics say there is scant evidence the drug is effective. The agency cleared the medication under its program for accelerated approval, basing the approval not on the clinical data but on the drug's ability to reduce amyloid beta in the brain. Agency officials said reducing the sticky clumps, which are thought to kill brain cells, was "reasonably likely" to benefit patients, including potentially slowing cognitive decline in people with the progressive, terminal disease.
Knopman, in his e-mail to the FDA, cited “biased questions” posed by the FDA’s review staff at the meeting last November of the Peripheral and Central Nervous System Drugs Advisory Committee. He also said that an FDA statistician, who had written that the data on the drug was “conflicting” and could be settled only by conducting another clinical trial, was not permitted to present “a full airing of his analyses.”
He also took issue with the agency’s approval of the drug based on a “biomarker” — the elimination of clumps of amyloid beta.
"Biomarker justification for approval in the absence of consistent clinical benefit after 18 months of treatment is indefensible," he said.
The FDA is not required to follow the advice of its outside experts, and a study found that 22 percent of the time from 2008 to 2015, the agency took actions that went against advisory committee recommendations. In the vast majority of cases, however, the FDA was more restrictive than the outside panels, deciding to keep a product off the market or limit its uses.