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 S. Knopman, a neurologist at the Mayo Clinic, said Wednesday in an email 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 email 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 S. Perlmutter, a neurologist at Washington University in St. Louis, resigned from the committee, according to the news publications Stat News and the Pink Sheet. Perlmutter told Stat in an email that he quit “due to this ruling by the FDA without further discussion with our advisory committee.”

Perlmutter did not immediately respond to an email from The Post requesting comment.

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.

Advocacy groups cheered the decision, noting that the drug was the first new treatment for Alzheimer’s in almost two decades. But opponents of the action said it represented a dangerous lowering of drug approval standards for a medication that Biogen said will be priced at about $56,000 per patient a year.

The resignations come as questions swirl around Aduhelm, including how it will be paid for and which patients will receive it.

Knopman, in his email 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.

Knopman was recused from the November meeting because he has been a site investigator for aducanumab.

Knopman has long been skeptical of aducanumab. He said in a comment filed to the committee docket last October that evidence of a benefit from the drug is “terribly weak,” adding, “Perfection may be the enemy of the good, but for aducanumab, the evidence doesn’t even rise to ‘good.’”

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.

Business Insider first reported Knopman’s resignation.

“I recognize that the role is advisory and yet I felt that the advisory committee in this situation was not well-treated,” Knopman told The Post. “And I think that I just don’t choose to put myself into that position in the future for the FDA.”

After the FDA announced its approval on Monday, Billy Dunn, the director of the agency’s Office of Neuroscience, wrote in a letter to the chairman of the advisory panel that the input from the committee in November prompted further discussions at the FDA and ultimately led to the decision to use the accelerated pathway.

Knopman said he would still offer the medication to his patients when it becomes available, describing that as a “completely separate issue.”

“I feel ethically bound to offer the treatment because FDA is the law of the land, and the drug is commercially available,” he said. “And I will present them 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.