FDA Advisers Evaluate Eli Lilly's Alzheimer's Drug: Will Donanemab Get the Green Light?

FDA advisers are meeting to assess whether Eli Lilly's experimental Alzheimer's drug, donanemab, is safe and effective. The trial design and potential risks, including brain swelling and bleeding, are key discussion points. The panel will decide if the benefits outweigh the risks for early-stage Alzheimer's patients.

Outside advisers to the U.S. Food and Drug Administration are meeting on Monday to assess whether Eli Lilly's experimental Alzheimer's drug donanemab is safe and effective, ahead of the agency's decision on approving the drug. The early discussion focused on some unique aspects of Lilly's trial, which differed significantly from the trial design of Eisai and Biogen Leqembi, which won U.S. approval after going through a similar advisory committee meeting.

Both drugs are designed to remove toxic beta amyloid plaques from the brains of people with early Alzheimer's disease. The antibody treatments, which succeeded in slowing disease progression in clinical trials, follow three decades of failed attempts to find drugs to fight the fatal mind-wasting disease. The FDA had been expected to rule on the drug earlier this year but called for the meeting so its independent panel of experts could weigh in. The agency is not obligated to follow the recommendations of its outside advisers, but typically does so.

The meeting has included presentations from both Lilly and FDA representatives. The agency's Teresa Buracchio said the FDA wants the panel's input on Lilly's trial design, which included people with high or intermediate levels of a second Alzheimer's protein called tau, but excluded people with little or no evidence of tau in their brain.

Tau is associated with brain cell death in patients with Alzheimer's. In documents submitted to the FDA, Lilly argued that tau imaging is not needed to determine who will benefit from the drug. Dr. Reisa Sperling, an Alzheimer's researcher at Mass General Brigham, told the panel she did not think it would be necessary or practical to require tau brain scans before use of the treatment.

Sperling expressed concern that requiring tau scans, which are not easily available, would delay the start of treatment and "further limit access of underserved populations." The FDA's Kevin Krudys, who reviewed Lilly's data, said it is not clear what the treatment effect would be in patients with no tau in their brain because such patients were not included in the main portion of the trial.

In a separate analysis, which looked at the drug's impact on underlying proteins in the brain, he said, "We think there should be some benefit, but it's hard to say how much." The agency is also seeking comment on an aspect of the trial design that allowed people to stop taking donanemab once a brain scan showed the amyloid has resolved.

Both issues could affect prescribing information for the drug. "Although cessation of dose may be a reasonable strategy, significant uncertainty still remains," Krudys said.

The panel is tasked with considering whether analyses of trial data presented by the FDA and the company show that the benefits of donanemab in slowing cognitive decline in patients with early stage disease outweigh its safety risks and making a recommendation. The Lilly drug and others in its class can cause fatal swelling or bleeding in the brain. Three people in the donanemab trial died from complications linked to the treatment.

With its approval of Leqembi, the FDA issued its strongest "boxed" warning about the risk of potentially dangerous brain swelling and bleeding for the entire class of amyloid-lowering drugs. FDA reviewers said last week that if approved, donanemab's risks of brain swelling and bleeding would be described in the warning.

Several analysts said they expect the drug to be approved. Wall Street on average forecasts donanemab sales of about $631 million next year, according to LSEG estimates. More than six million Americans have some form of the memory-robbing condition, according to the Alzheimer's Association. That figure is projected to rise to nearly 13 million by 2050.

(This story has not been edited by Devdiscourse staff and is auto-generated from a syndicated feed.)