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. Instead, the FDA will require donanemab to undergo review by a panel of independent experts, the drug’s maker, Eli Lilly and Company, said Friday.
“The FDA has informed Lilly that it wants to understand further issues related to the evaluation of the safety and efficacy of donanemab, including the safety results in patients treated with donanemab and the efficacy implications of the unique trial design,” the FDA said. company in statement.
The decision is likely to surprise many Alzheimer’s specialists, doctors and patients who expected the drug to be on the market soon. The FDA’s move came as a surprise to the company, which had planned to greenlight the drug in the first quarter of this year.
“We didn’t expect this,” Anne White, Lilly’s executive vice president and president of its neuroscience division, said in an interview. He said that while the FDA often calls such independent advisory panels when it has questions about drugs, it was unusual for it to do so “at the end of the review cycle and after the action date that the FDA had given us.”
The FDA has said nothing publicly about the move, which will delay any decision on 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 held a hearing.
“The FDA made a commitment to us to move quickly, so hopefully they would take action soon after the advisory,” Ms. White said.
The decision to convene an advisory committee reflects the high stakes and difficult history of developing treatments for Alzheimer’s disease. The disease afflicts more than six million Americans and currently has no cure and no drug that can restore memory loss or reverse cognitive decline.
For years, the field was marred by failed drug trials. But donanemab, a once-a-month infusion, belongs to a new class of drugs that experts hope could help patients by attacking a protein, amyloid, that builds up in plaques in the brains of people with Alzheimer’s.
Last year, the FDA 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 disease.
The new drugs are considered only a first step in a potentially fruitful direction because they may not slow their 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 antiamyloid class, Aduhelm, was controversial because it had weak evidence; Biogen, the drug’s maker, recently abandoned it.)
Donanemab was expected to win approval easily because data showed the drug could also modestly slow cognitive decline in people with mild symptoms and the safety risks were similar to those of Leqembi. Because the design of the donanemab trial was different from that of Leqembi and included some patients with more complex medical problems, the trials of the two drugs cannot be directly compared.
The donanemab trial had two unusual aspects that the FDA indicated it would ask the advisory panel to evaluate, said Dr. John Sims, Lilly’s medical director and head of donanemab’s clinical trials.
One feature would be especially attractive to patients: trial participants stopped taking donanemab after their amyloid plaques had cleared to a certain level — about a year for half of the participants who started donanemab — and their cognitive decline continued to slow. Lilly scientists have estimated that it will take nearly four years for amyloid levels to rise above the threshold again.
Dr. Sims said he thought the FDA wanted to understand more about stopping treatment because “it’s very unique,” and regulators may want to explore whether other anti-amyloid drugs could stop at a certain point.
Ms. White said that among doctors and patients, “there’s a lot of excitement about this idea that once you’ve cleared your target, you don’t have to subject patients to additional infusions and visits.”
The other unusual feature of the trial involved another protein, tau, which forms tangles in the brain after amyloid builds up. 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 a greater slowing of cognitive decline — supporting a widely held theory that treating patients as early as possible in the disease process provides a better chance of slowing symptoms.
Dr. Sims said measuring tau was “informative, but not necessary to initiate treatment for patients, and we had therapeutic effects across the tau spectrum.” He said the FDA had not indicated “the specifics of what they want to talk about” about tau, just that it was an issue the advisory committee would consider.
Ms White said: “There are some people here at Lilly who have been working on this for 35 years, so you can imagine it must have been a disappointment for them not to bring it to patients right now.” But he said the company was confident in its data and would spend the next few months thinking about “additional analysis that we can do to answer any questions that somebody might ask us.”
