The Food and Drug Administration has decided to delay action on a closely watched Alzheimer’s drug, donanemab, which the agency was widely expected to approve this month. The F.D.A. will instead require donanemab to undergo the scrutiny of a panel of independent experts, the drug’s maker, Eli Lilly and Company, said Friday.
“The F.D.A. has informed Lilly it wants to further understand topics related to evaluating the safety and efficacy of donanemab, including the safety results in donanemab-treated patients and the efficacy implications of the unique trial design,” the company said in a statement.
The decision is likely to surprise many Alzheimer’s experts, doctors and patients who had expected the medication would soon be on the market. The F.D.A.’s move was startling to the company, which had been planning for the agency to greenlight the drug during the first quarter of this year.
“We were not expecting this,” Anne White, an executive vice president of Lilly and president of its neuroscience division, said in an interview. She said that while the F.D.A. often calls on such independent advisory committees when it has questions about drugs, it was unusual to do so “at the end of the review cycle and beyond the action date that the F.D.A. had given us.”
The F.D.A. did not say anything publicly about the move, which will delay any decision about whether to approve donanemab until at least later this year. Lilly officials said they expected it would be a few months before the advisory committee holds a hearing.
“The F.D.A. did commit to us to move quickly, so we would hope that they would then take action shortly after the advisory committee,” Mrs. White said.
The decision to convene an advisory committee reflects the high stakes and rocky history of developing treatments for Alzheimer’s. The disease afflicts more than six million Americans and currently has no cure and no medication that can restore memory loss or reverse cognitive decline.
For years, the field was marked by failed drug trials. But donanemab, an infusion given once a month, belongs to a new class of drugs that experts hope might help patients by attacking a protein, amyloid, that clumps into plaques in the brains of people with Alzheimer’s.
Last year, the F.D.A. approved another drug in the class, Leqembi, made by Eisai and Biogen. An infusion given every two weeks, Leqembi can modestly slow cognitive decline in the early stages of Alzheimer’s.
The new drugs are considered only a first step in a potentially fruitful direction because they may not slow decline enough to be noticeable to patients or families, experts say. The drugs also carry significant safety risks, including swelling and bleeding in the brain.
(The first drug approved in the anti-amyloid class, Aduhelm, was controversial because it had weak evidence; Biogen, the manufacturer of the drug, recently abandoned it.)
Donanemab was expected to win approval easily because data showed that the drug could also modestly slow cognitive decline in people with mild symptoms, and the safety risks were similar to those of Leqembi. Because donanemab’s trial design was different than Leqembi’s and included some patients with more complex medical problems, the two drugs’ trials cannot be directly compared.
Donanemab’s trial had two unusual aspects that the F.D.A. indicated it would ask the advisory committee to evaluate, said Dr. John Sims, a medical director with Lilly and the leader of the donanemab clinical trials.
One feature would be particularly appealing to patients: Participants in the trial stopped receiving donanemab after their amyloid plaques were cleared to a certain level — about a year for half the participants who started off with donanemab — and their cognitive decline kept slowing. Lilly scientists have estimated it would take nearly four years for amyloid levels to bump up over the threshold again.
Dr. Sims said he believed the F.D.A. wanted to understand more about stopping treatment because “it’s very unique” and regulators might want to explore whether other anti-amyloid drugs could be halted at a certain point.
Mrs. White said that among doctors and patients, “there’s a lot of enthusiasm for this concept of once you clear the target that you’re going after, that you don’t need to put patients through additional infusions and visits.”
The other unusual feature of the trial involved another protein, tau, which forms tangles in the brain after amyloid accumulates. Higher tau levels are more closely associated with memory and thinking problems.
The donanemab trial divided participants into groups with high tau levels and intermediate tau levels. People with intermediate tau levels had more slowing of cognitive decline — supporting a widespread theory that treating patients as early as possible in the disease process provides a better chance of slowing symptoms.
Dr. Sims said that measuring tau was “informative, but not necessary for instituting therapy for patients, and we had treatment effects across the entire spectrum of tau.” He said that the F.D.A. had not indicated “the specifics of what they want to talk about” involving tau, just that it was a subject the advisory committee would consider.
Mrs. White said, “There’s some people here at Lilly that have been working on this for 35 years, and so you can imagine that this was certainly a disappointment to them not to bring this to patients right now.” But she said the company was confident in its data and would spend the next few months thinking about “additional analyses that we can do to help answer any questions that someone might pose at us.”
