Eli Lilly & Company, the maker of anti-amyloid Alzheimer’s treatments, was expecting the FDA to approve its experimental drug donanemab this month. However, the FDA announced that it will hold a panel with external advisors to evaluate the safety and efficacy of donanemab before making a decision later this year. While the FDA’s decision was surprising, experts believe a cautious approach is beneficial for patients given that there is little evidence of the drug’s benefits. The committee established by the FDA will convene later this year before making a final decision on approval.
Donanemab is one of three monoclonal antibody treatments for Alzheimer’s, along with aducanumab and lecanemab, that work by clearing amyloid plaques characteristic of the disease. The FDA granted accelerated approval to aducanumab and lecanemab based on promising trial results. The establishment of a committee to evaluate donanemab was unexpected due to its similarities in efficacy and safety to lecanemab. The committee will focus on the added benefit on efficacy, unique dosing schedule regimen, and tau imaging used for entry into the trial.
Dr. Howard Fillit, co-founder and chief science officer of the Alzheimer’s Drug Discovery Foundation, believes that donanemab will ultimately be approved by the FDA based on trial data and the safety measures in place to monitor risks. In a phase 3 trial, donanemab slowed cognitive decline by 22% in people with low/medium levels of tau and 35% in individuals with low/medium levels of tau compared to placebo. However, the risks of amyloid-related imaging abnormalities (ARIA) such as brain swelling or bleeding must be carefully monitored. The study population was also predominantly white, raising concerns about generalizability.
Dr. Clifford Segil, a neurologist at Providence Saint John’s Health Center, hopes that the FDA committee will ultimately not approve donanemab, citing the drug’s risks. He believes that anti-amyloid medications have not significantly improved memory loss in patients and have caused severe side effects. He argues that the risks of brain bleeds and edema outweigh any benefits and hopes that donanemab’s revoked FDA application will signify the end of such medications being used for Alzheimer’s treatment. However, Dr. Fillit believes that the benefits of donanemab outweigh the risks, especially with careful monitoring and precautions in place for patients.
Currently available treatments for Alzheimer’s can help manage symptoms but not change the course of the disease. Donanemab’s slowing of cognitive decline in clinical trials has shown promise, but the risks associated with ARIA must be carefully monitored. The FDA’s decision to convene a committee to evaluate the drug’s safety and efficacy reflects the need for a cautious approach to approving new treatments. Ultimately, the decision on donanemab will impact the treatment options available for Alzheimer’s patients and highlight the ongoing challenges in developing effective therapies for this devastating disease.