Seven members of an FDA advisory panel criticized the agency's decision to approve Biogen's Alzheimer's drug Aduhelm in an opinion piece published July 28 in The New England Journal of Medicine.
The members of the FDA's Peripheral and Central Nervous System Advisory Committee — which include physicians from Harvard Medical School in Boston, the Mayo Clinic in Rochester, Minn., and the University of California San Francisco — advised the FDA on Aduhelm, all voting not to approve it. Three of the members resigned from the panel after the FDA's decision to approve the drug.
The members wrote that the approval was a "regulatory failure" that should be investigated "expeditiously" to learn how it happened and make sure it doesn't happen again.
The FDA granted accelerated approval to Aduhelm on the basis that its ability to reduce a toxic protein found in the brain called beta amyloids makes clinical improvement reasonably likely for Alzheimer's patients. But it hasn't been proven that reducing the number of beta amyloids actually slows cognitive decline, the panel members wrote.
They said the committee was never told that the FDA would use beta amyloids as a reference point for approval. In fact, the lead FDA scientist told the advisory panel the agency wasn't using beta amyloids as a factor in approving the drug, the panel members wrote.
The members also criticized the fact that the initial label the FDA put on the drug allowed it to be used on anyone with Alzheimer's, though it was only tested in patients with mild cognitive impairment or mild dementia caused by Alzheimer's.
The label has since been updated to narrow the drug's use to those patients, but it still doesn't specify that physicians should check if patients have elevated levels of beta amyloids before prescribing the drug. Up to half of people with mild cognitive impairment and a presumptive diagnosis of Alzheimer's don't have elevated levels, the panel members wrote.
"Although FDA regulation is separate from coverage and reimbursement questions, the scientifically unjustified label may lead to billions of dollars in unnecessary Medicare expenditures, even if a national coverage determination is ultimately made," the panel members wrote.
They argued that the overwhelming undermet need for Alzheimer's treatments should drive research investments, not lowering of regulatory standards.
They concluded by saying the effects of the decision are already being reflected in announcements by two other drugmakers that said they will seek accelerated approval for their Alzheimer's drugs based on their ability to reduce beta amyloids.
Read the full opinion piece here.