FDA Panel Backs New Alzheimer's Drug, Donanemab

An advisory panel for the U.S. Food and Drug Administration (FDA) recommended in favor of Eli Lilly's new drug, donanemab, for early-stage Alzheimer's disease. The decision, made on Monday, concluded that the benefits of the drug, despite potential risks such as brain swelling and bleeding, outweighed its harms. The panel's unanimous vote was influenced by the significant impact of Alzheimer's, which affects over 6 million Americans and currently has no cure.

Eli Lilly presented data showing that donanemab slowed cognitive decline in patients by 37% over 18 months compared to a placebo. Initially expected to receive approval earlier this year, the FDA chose in March to have an independent advisory panel review the drug. The panel recognized the severity of Alzheimer's disease and determined that even modest benefits are meaningful given the lack of effective treatments.

Donanemab targets amyloid, a brain protein associated with Alzheimer's. This approach aligns with two other recently approved amyloid-fighting drugs: Leqembi, by Eisai and Biogen, and Aduhelm, also by Biogen. Leqembi, approved last year, showed similar risks and benefits to donanemab. Aduhelm was approved in 2021 but later discontinued due to insufficient evidence of its efficacy.

The panel's decision drew mixed reactions. Joanne Pike, President and CEO of the Alzheimer’s Association, viewed the approval of more Alzheimer's treatments as a significant advancement. She emphasized the need for diverse treatments targeting various aspects of the disease, which could lead to combination therapies offering greater safety and efficacy.

Conversely, some experts were critical. Dr. Robert Steinbrook, director of Public Citizen’s Health Research Group, expressed disappointment, arguing that the FDA should not repeat the mistakes made with aducanumab and lecanemab. He highlighted that all three drugs posed substantial health risks, including brain swelling and bleeding, and questioned whether their benefits justified these risks. Steinbrook suggested that donanemab should not be approved due to these concerns.

Trial data indicated that donanemab slowed cognitive decline by approximately 4½ to 7½ months compared to a placebo. However, three patients on donanemab died from brain swelling or bleeding linked to the drug. Another point of discussion was that participants ceased treatment once their amyloid levels dropped, which some panel members supported to avoid ongoing risks and costs. However, there were concerns about how patients would be monitored after stopping the drug and the timing of potential interventions if amyloid levels rose again.

Dr. Constantino Iadecola of Weill Cornell Medicine raised questions about the monitoring process post-treatment. He emphasized the need for ongoing observation and clarity on when intervention would be necessary if amyloid levels increased.

Lilly scientists estimated that it would take nearly four years for amyloid levels to rise above the threshold again after stopping treatment. As the debate continues, the need for effective Alzheimer's treatments remains urgent, with ongoing discussions about balancing benefits and risks.

In summary, the FDA advisory panel's recommendation for donanemab highlights the complexities in evaluating new treatments for Alzheimer's disease. While the decision marks progress, it also underscores the ongoing challenges in addressing the substantial health risks associated with amyloid-targeting therapies.