Eli Lilly & Company, the maker of anti-amyloid Alzheimer’s treatments, has been working on getting its experimental drug donanemab approved by the FDA. However, the FDA has decided to hold a panel with external advisors to evaluate the safety and efficacy of this drug before making a final decision later in the year. While this decision came as a surprise to many, experts believe that a more cautious approach would be beneficial given that the drug is still in early trials and there is limited evidence of its benefits. Donanemab is one of three monoclonal antibody treatments aimed at clearing amyloid plaques that are characteristic of Alzheimer’s disease. Although it showed slowed clinical progression in early trials, it also produced adverse effects such as brain swelling.
Alzheimer’s disease affects millions of people worldwide, with a significant proportion of them having a buildup of amyloid and tau proteins in their brains. In addition to donanemab, two other drugs, aducanumab and lecanemab, have been given accelerated approval by the FDA based on promising trial results. The establishment of a committee to evaluate donanemab by the FDA is not unprecedented, but due to similarities in efficacy and safety results with Leqembi, it was unexpected. The committee will specifically look at the added benefit on efficacy, the unique dosing schedule of the drug, and the use of tau imaging in clinical care. While some experts hope for the FDA to not approve donanemab due to its risks and questionable benefits, others like Dr. Howard Fillit believe that the trial data and safety measures in place justify its approval.
Donanemab was shown to slow cognitive decline in early Alzheimer’s patients by a significant percentage in a phase 3 trial. However, there were risks associated with the drug, including amyloid-related imaging abnormalities (ARIAs) that could lead to brain swelling or bleeding. The trial also raised concerns about the lack of diversity in the study population, with over 91% of participants being white. Dr. Fillit acknowledges the existence of risks associated with donanemab but emphasizes the importance of careful monitoring and assessment before and during treatment. Monitoring brain bleeding with MRIs and considering the patient’s APO lipoprotein E genotype are among the safety measures recommended to minimize these risks.
Despite the potential benefits of slowing cognitive decline in Alzheimer’s patients, some experts like Dr. Clifford Segil remain skeptical about the use of drugs like donanemab due to the risks involved. Dr. Segil believes that the risks of brain bleeds and edema outweigh any potential benefits, and he, along with many other neurologists, will refrain from using drugs in this family for treatment. He hopes that the FDA’s decision to establish a committee for evaluating donanemab may signal the beginning of the end for anti-amyloid medications being approved for Alzheimer’s dementia treatment. With conflicting opinions among experts regarding the approval of donanemab, the outcome of the FDA committee’s evaluation will have a significant impact on the future of Alzheimer’s treatments and the risks associated with these innovative therapies.
