Eli Lilly and Company (NYSE: LLY) has announced that the U.S. Food and Drug Administration (FDA) plans to convene a meeting of the Peripheral and Central Nervous System Drugs Advisory Committee (PCNS) to discuss the Phase 3 TRAILBLAZER-ALZ 2 trial, which assessed the efficacy and safety of donanemab in early symptomatic Alzheimer’s disease.
The FDA has indicated a desire to delve deeper into topics concerning the evaluation of donanemab’s safety and efficacy, including the safety outcomes among patients treated with donanemab and the efficacy implications of the unique trial design of the TRAILBLAZER-ALZ 2 study. This design included a limited-duration dosing regimen based on amyloid plaque assessment and the inclusion of participants based on tau levels.
The FDA has not yet set a date for the advisory committee meeting on donanemab, consequently delaying the anticipated FDA action on donanemab beyond the first quarter of 2024. While it’s uncommon for an advisory committee to occur after the expected FDA action date, this meeting follows similar discussions for two other FDA-approved amyloid plaque-targeting therapies.
Anne White, executive vice president of Eli Lilly and Company and president of Lilly Neuroscience, expressed confidence in donanemab’s potential to provide significant benefits to individuals with early symptomatic Alzheimer’s disease. Despite the unexpected timing of the advisory committee meeting, Lilly looks forward to presenting further TRAILBLAZER-ALZ 2 results and contextualizing donanemab’s efficacy alongside its safety profile.
TRAILBLAZER-ALZ 2 is a Phase 3 study involving participants aged 60-85 years with early symptomatic Alzheimer’s disease, comprising mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease. The trial enrolled 1,736 participants across eight countries, selected based on cognitive assessments in conjunction with amyloid plaque and tau imaging.
Compared to similar trials of other amyloid plaque-targeting therapies, TRAILBLAZER-ALZ 2 participants were at more advanced stages of their disease. Donanemab demonstrated benefits across all participant groups, with those in earlier disease stages experiencing the most pronounced results. The study also highlighted clinical benefits with a limited-duration treatment regimen, with nearly half of participants completing their treatment within six or 12 months. Notably, the primary risk associated with donanemab is amyloid-related imaging abnormalities (ARIA), which can be severe and life-threatening, alongside other commonly reported risks such as infusion-related reactions, headache, and nausea.
The Phase 3 TRAILBLAZER-ALZ 2 study results were published in the Journal of the American Medical Association (JAMA), and Lilly continues to explore donanemab in multiple clinical trials.
This development does not impact Lilly’s financial guidance for 2024.
