FDA advisors strongly back new Alzheimer’s drug, despite risks and limitations

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An advisory committee to the Food and Drug Administration has recommended that the federal agency approve Alzheimer's drug donanemab. / AP

Advisors to the Food and Drug Administration have recommended unanimously that the agency approve the Alzheimer’s drug donanemab.

At a meeting Monday, the Peripheral and Central Nervous System Drugs Advisory Committee voted 11-0 that donanemab is effective at slowing down Alzheimer’s in the disease’s early stages and that the drug’s benefits outweigh its risks.

All 11 committee members also recommended that doctors and patients have the option of halting monthly infusions if tests show that most amyloid plaques — a hallmark of Alzheimer’s — have been removed from the brain.

Studies suggest that would mean most patients could discontinue the drug, made by Eli Lilly, within a year.

The evidence that donanemab works is “very strong,” said Dean Follmann, a committee member and statistician at the National Institutes of Health. And although it does not stop the disease, it slows the progression enough to be “meaningful to patients.”

If the FDA follows the committee’s recommendation, donanemab would join a similar drug, sold under the brand name Leqembi, which was approved by the agency in 2023.

During a day-long discussion, committee members noted that, if approved, donanemab would have some apparent advantages over Leqembi. The older drug is given every two weeks indefinitely, while the newer one is given monthly and could be stopped for some patients.

Leqembi, made by Eisai in partnership with Biogen, costs more than $26,000 a year. Eli Lilly hasn’t announced what donanemab would cost.

Donanemab, which targets the amyloid plaques that build up in the brain of Alzheimer’s patients, has taken an unusually long time to work through the approval process.

Eli Lilly applied to the FDA for “accelerated approval” in January 2023, but the agency said it needed more safety data.

Both donanemab and Leqembi can cause swelling and bleeding in the brain. These effects are usually not symptomatic, but can be serious and have been linked to several deaths.

After being initially rebuffed by the FDA, Eli Lilly applied for traditional approval in mid-2023, which usually would have resulted in a decision by the end of the year.

Instead, the agency announced in early 2024 that it would convene its advisory committee before making a decision.

At Monday’s meeting, the committee heard from doctors and patients who urged them to approve the drug.

“It is critical to do whatever we can to have an impact to slow this terrible, inexorably progressive disease,” said Dr. Reisa Sperling, who directs the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital in Boston and has served as a consultant to several drug companies.

“Donanemab has been very, very helpful to me,” said Myra Garcia, 65, an Alzheimer’s patient who lives in Upland, California. “I have been on the clinical trial for about 2 to 3 years, and I can tell you that I have had not a single bit of problem with it.”

The committee discussed the risks associated with donanemab at length.

Members were especially concerned about people who carry two copies of a gene called APOE4. The gene greatly increases the risk that they will get Alzheimer’s, but it also greatly increases the risk of brain bleeding or swelling when they receive donanemab.

But Colette Johnston, the patient representative on the committee, said even higher-risk patients should have access to the drug.

“Yes, there is risk,” she said. “But when you get a diagnosis of Alzheimer’s, you don’t have anything but risk.”

Sperling echoed that idea.

“We have to take Alzheimer's disease seriously,” she said. “And serious diseases require aggressive treatments.”

The committee recommended that if donanemab is approved, doctors and patients should be given educational materials that clearly explain the drug’s risks.

Members also said researchers need to learn more about the long-term consequences of stopping treatment. For example: Do amyloid plaques re-appear after several years, and if so, should doctors put their patients back on donanemab?

The FDA is expected to act on the committee’s recommendation in the next few months.