FDA to convene advisory committee meeting to discuss the TRAILBLAZER-ALZ 2 study of donanemab.- Eli Lilly

The FDA has informed Lilly it wants to further understand topics related to evaluating the safety and efficacy of donanemab, including the safety results in donanemab-treated patients and the efficacy implications of the unique trial design of the TRAILBLAZER-ALZ 2 study, including its limited-duration dosing regimen that allowed patients to complete treatment based on an assessment of amyloid plaque and the inclusion of participants based on tau levels.

The date of the advisory committee meeting for donanemab has yet to be set by the FDA, and, as a result, the timing of expected FDA action on donanemab will be delayed beyond the first quarter of 2024. While it is unusual for an advisory committee to occur after the anticipated FDA action date, the advisory committee meeting for donanemab follows similar meetings for the two other amyloid plaque-targeting therapies the FDA has approved.

< TRAILBLAZER-ALZ 2 is a Phase III, double-blind, placebo-controlled study to evaluate the safety and efficacy of donanemab in participants ages 60-85 years with early symptomatic Alzheimer's disease (MCI or mild dementia due to Alzheimer's disease) with the presence of confirmed Alzheimer's disease neuropathology.

Alzheimer's disease is a progressive and fatal disease that in its early symptomatic stages affects 6-7.5 million Americans. The trial enrolled 1,736 participants, across eight countries, selected based on cognitive assessments in conjunction with amyloid plaque imaging and tau staging by positron emission tomography (PET) imaging.

Compared to participants in similar trials of other amyloid plaque-targeting therapies, the TRAILBLAZER-ALZ 2 participants were more progressed in their disease. All groups of trial participants, regardless of tau level, benefited from treatment with donanemab, with patients in earlier stages of the disease experiencing the strongest results. Donanemab also demonstrated clinical benefits using a limited-duration treatment regimen, with nearly half of clinical trial participants completing their course of treatment in six or 12 months.

The key risk associated with donanemab is amyloid related imaging abnormalities, or ARIA, which can be serious and life-threatening. Other most commonly reported risks include infusion-related reactions, headache and nausea.