Expert advisers unanimously approve new Alzheimer’s drug despite safety risks

A panel of independent advisers overseeing the Food and Drug Administration unanimously sanctioned the latest experimental drug for Alzheimer’s disease on Monday, emphasizing that its benefits outweigh the associated risks.

Alzheimer’s disease affects over six million Americans, lacking a cure or effective treatment to reverse memory loss or cognitive decline. Developed by Eli Lilly under the name donanemab, the drug exhibited a modest slowdown in cognitive deterioration among early-stage patients but posed notable safety hazards such as brain swelling and bleeding.

Despite these risks, the committee emphasized the severe impact of Alzheimer’s, deeming even a slight improvement as valuable given the current treatment landscape. While the FDA typically adheres to the guidance of its advisory panels, there have been exceptions in the past.

Donanemab targets the hypothesis that Alzheimer’s originates from the accumulation of amyloid protein clusters in the brain, subsequent to neuronal death-triggering reactions. Recent approvals of similar amyloid-targeting drugs like Leqembi and Aduhelm have shown similar risk-benefit profiles, although Aduhelm was discontinued due to insufficient evidence of efficacy.

Originally slated for approval earlier this year, the FDA decided in March to subject donanemab to further evaluation by an independent advisory committee, surprising Eli Lilly. The vote, lauded by Dr. Daniel Skovronsky of Lilly, marked a significant milestone in the company’s two-decade mission to address Alzheimer’s disease, with plans to initiate studies aimed at preempting symptoms.

Discussions during the committee meeting addressed unique aspects of donanemab’s trials, especially the cessation of drug intake once amyloid clearance was achieved. Some experts questioned this practice, suggesting a reevaluation of treatment protocols post-clearance.

Delivered via intravenous infusions akin to Leqembi, donanemab’s subtle cognitive benefits may pose challenges in patient and family perception. Notably, the drug’s effects may be imperceptible to those receiving it, and the potential disease progression in the absence of treatment remains largely unknown.

Lilly’s data submission from a 76-week trial involving 1,736 early-stage Alzheimer’s patients demonstrated the drug’s impact on cognitive performance compared to a placebo. The research warranted the committee’s unanimous vote, indicating a cautious yet optimistic step forward in Alzheimer’s therapeutics.