The FDA’s Peripheral and Central Nervous System Drugs Advisory Committee (PCNS) has voted unanimously in favor of Eli Lilly's experimental Alzheimer's drug, donanemab, citing its benefits outweigh the risks for early-stage patients.
While the agency’s decision is not contingent on the meeting’s outcome, the nod hints at a clear path for the FDA's final decision. Back in March, Lilly revealed that the FDA's decision, originally slated for late March, would be delayed because the agency decided it needed to convene an AdComm meeting. Lilly said that PCNS wanted to dig deeper into the safety and efficacy of donanemab by examining the safety results in patients treated with the drug and the efficacy implications of the unique trial design of the TRAILBLAZER-ALZ 2 study.
The study featured a limited-duration dosing regimen, allowing patients to complete treatment based on amyloid plaque assessment and included participants based on tau protein levels. The trial ended up demonstrating a 29% reduction in memory decline among Alzheimer's patients.
Concerns were raised over ARIA (amyloid-related imaging abnormalities) occurrences. ARIA includes conditions like brain swelling (edema) and microhemorrhages (small brain bleeds) that can be detected through MRI scans. These abnormalities have been observed in patients taking other Alzheimer's drugs, such as Biogen's Aduhelm and Eisai's Leqembi. ARIA is a significant safety consideration as it can lead to serious adverse effects, including death.
But despite reservations over safety, including brain swelling and bleeding, the panel highlighted the trial's flexible treatment approach. This method allows discontinuation once amyloid plaques clear, posing challenges for physicians in managing treatment timelines.
Donanemab targets and removes beta-amyloid plaques, toxic proteins that accumulate in the brains of people with Alzheimer's. The drug is designed to bind to these plaques, marking them for clearance by the immune system. By reducing the levels of beta-amyloid, donanemab aims to slow the progression of memory and cognitive decline in patients with early-stage Alzheimer's disease.
