FDA panel makes the call on much-anticipated Alzheimer's drug donanemab

A Food and Drug Administration advisory panel on Monday endorsed the experimental Alzheimer's drug donanemab, which studies showed slowed early stages of the fatal mind-robbing disease.

The recommendation came despite pointed questions from advisory committee members about the potential side effects of Eli Lilly's drug, an antibody that removes beta-amyloid that accumulates in the brains of patients with Alzheimer's disease.

The FDA is not compelled to follow the recommendation of the advisory committee of outside experts, but it often does so. A notable exception was when the advisory committee recommended the agency reject Biogen's amyloid-clearing drug aducanumab; nevertheless, the FDA in 2021 approved the drug. Biogen halted sales and gave up ownership of the drug earlier this year.

During the FDA's Peripheral and Central Nervous System Advisory Committee hearing on Monday, officials at Eli Lilly said clinical trials showed the drug slowed cognitive and functional decline for people with early stages of the disease.

The advisory committee unanimously agreed the studies showed that donanemab was effective at treating people with an early stage of Alzheimer's disease, a stage known as mild cognitive impairment. The panel also said the benefits of the drug outweighed potential risks for people with early stages of the disease.

Last July, a study published in the Journal of the American Medical Association reported Eli Lilly's Alzheimer's drug slowed decline by 35% compared with a placebo group based on a measure of daily activities such as driving, managing finances and talking about current events.

Like other drugs that target and clear amyloid from the brain, studies showed donanemab had side effects that included brain swelling and tiny bleeds that could be detected via MRI. 

At Monday's hearing, Eli Lilly officials said people taking donanemab had a slightly higher rate of MRI-visible injuries, known amyloid-related imaging abnormalities (ARIA), compared with people who took a placebo. Most people who had serious reactions to the drug tended to get them during the first six drug infusions and they decreased over time, Lilly experts said.

Three people died from ARIA-related injuries during the study, and another two who continued taking the drug after the study finished also died from ARIA injuries. Lilly officials said 2% of people who received donanemab during the study died compared with 1.7% of people who received a placebo.

Several panel members questioned Eli Lilly experts about the higher risk some patients face who carry two copies of the Alzheimer's susceptibility gene APOE4. Though the panel did not vote on specific recommendations for people who carry two copies of APOE4, some panel members said these patients were at risk of side effects and appeared to benefit less from donanemab.

Other members of the panel urged Eli Lilly to continue to study the effect of the drug on Black and Hispanic patients, people with Down syndrome and others with a known family risk for the disease.

Reisa Sperling, a professor of neurology at Harvard Medical School, testified about the benefits and risks of the drug. She said it's crucial to inform doctors that they should monitor for potential side effects and for doctors to discuss with patients the risks and benefits of the drug.

She also said side effects are inherent with amyloid-clearing drugs, which appear to be the best-known way to slow Alzheimer's disease progression.

"We haven't yet hit the full home run," Sperling said. "But right now it is critical to do whatever we can to have an impact to slow this terrible, inexorably progressive disease and allow older people to be able to enjoy this time with their families."

Michelle Papka, founder and president of the Cognitive and Research Center, a clinical trial site in Springfield, New Jersey, said donanemab is a better option for some patients than the treatments now available.

"Donanemab is not a miracle cure. It does not stop cognitive decline," Papka said. "But it could be part of an effective cocktail, and we've got to start somewhere."

Last year, the FDA approved Eisai and Biogen's drug Leqembi but required the drug provide a warning about the drug's known side effects, which include brain swelling and tiny bleeds. Leqembi was the first amyloid-targeting drug to gain traditional FDA approval. Medicare said it would cover Leqembi and other anti-amyloid drugs that gain traditional FDA approval as long as prescribing doctors participate in a registry, or a database that tracks how well the drug works.