A sign for the Food and Drug Administration is seen outside of headquarters on July 20, 2020 in White Oak, Maryland.
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A third member of a key advisory body to the Food and Drug Administration has resigned over the agency’s controversial decision to approve Biogen’s new Alzheimer’s drug Aduhelm, CNBC has learned.
Dr. Aaron Kesselheim, professor of medicine at Harvard Medical School, said the agency’s decision on Biogen was “probably the worst drug approval decision in recent US history,” according to his resignation letter received by CNBC.
“At the last minute the agency switched its review to the accelerated approval path based on the questionable premise that the drug’s effect on the amyloid of the brain would likely help patients with Alzheimer’s disease,” he wrote on retiring from the peripheral and central nervous system of the FDA advisory committee.
He was “clear”, he wrote, that the agency “is currently not in a position to adequately integrate the scientific recommendations of the committee into its approval decisions”.
“This will undermine the care of these patients, public trust in the FDA, the pursuit of useful therapeutic innovations, and the affordability of the health system,” he said.
Biogen’s shares rose 38% Monday after the FDA approved the biotech company’s drug, the first drug approved by U.S. regulators to slow cognitive decline in people with Alzheimer’s disease, and the first new drug for the disease for nearly two decades.
Biogen’s drug targets a “sticky” compound in the brain known as beta-amyloid that scientists expect to play a role in the devastating disease.
The FDA approved the drug under a program called accelerated approval, typically used for cancer drugs, in the expectation that the drug would slow cognitive decline in Alzheimer’s patients. The agency granted approval on condition that Biogen conducts another clinical study.
The agency’s decision differed from the advice of its independent panel of external experts, which unexpectedly refused to approve the drug last fall, citing inconclusive data. At that time, the committee also criticized the agency staff for checking the data too positively.
At least two other members of the FDA panel have resigned due to the agency’s decision on the drug. Mayo Clinic neurologist Dr. David Knopman, and Washington University neurologist Dr. Joel Perlmutter, have also submitted letters of resignation.
“I was very disappointed with the way the FDA handled the input from the advisory committee,” Knopman told Reuters. “I don’t want to be put in such a position again.”
Federal agencies have come under intense pressure from friends and family members of Alzheimer’s patients to speed up the drug scientifically known as aducanumab, but the road to regulatory approval has been controversial since it showed promise in 2016.
In March 2019, Biogen withdrew from development of the drug after analysis by an independent group found it was unlikely to work. The company then shocked investors a few months later by announcing that it would apply for regulatory approval for the drug after all.
When Biogen filed for approval for the drug in late 2019, its scientists said a new analysis of a larger data set showed that aducanumab “reduces clinical decline in patients with early-stage Alzheimer’s disease.”
Alzheimer’s experts and Wall Street analysts were immediately skeptical, wondering whether the clinical trial data was enough to prove the drug works and whether approval could make it difficult for other companies to enroll patients in their own drug trials.
Some doctors have said they won’t prescribe aducanumab because of the mixed data package that supports the company’s application.
– Reuters contributed to this report.