FDA Sets Date of Advisory Committee Meeting for Donanemab in Alzheimer’s Disease

The FDA will convene an in-person meeting of the Peripheral and Central Nervous System Drugs Advisory Committee on Monday, June 10, 2024, to discuss the phase 3 trial of Lilly’s donanemab to treat patients with early symptomatic Alzheimer’s disease.

Regulators had said previously they want to discuss the safety results in donanemab-treated patients and the efficacy implications of the unique trial design of the TRAILBLAZER-ALZ 2 phase 3 study. Specifically, they want to discuss the trial’s use of 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.

Donanemab was under review for full approval to treat patients with early Alzheimer’s disease. A decision had been expected by the end of 2023. The FDA had previously said it wouldn’t grant accelerated approval of donanemab to treat patients with early Alzheimer’s disease. In a complete response letter in January 2023, the agency indicated that there too few patients with at least 12 months of data provided in Lilly’s submission. Lilly had resubmitted the application in July 2023 for full approval.

Lilly continues to study donanemab in multiple clinical trials, including TRAILBLAZER-ALZ-3, studying donanemab for the prevention of Alzheimer’s disease.

Related: FDA to hold Advisory Committee on Donanemab in Alzheimer’s Disease

Full results from the TRAILBLAZER-ALZ 2 trial show that donanemab slowed cognitive and functional decline in people with early symptomatic Alzheimer’s disease. Almost half of participants at earlier stage of disease on donanemab had no clinical progression at one year. Additionally, analyses of patients at earliest stage of the disease had even greater benefit, with 60% slowing of decline compared with placebo.

The data were shared at the 2023 Alzheimer’s Association International Conference and also published in the Journal of the American Medical Association.

The TRAILBLAZER-ALZ 2 enrolled 1,736 patients with a broad range of cognitive scores and amyloid levels. Patients were stratified by their level of tau, a predictive biomarker for disease progression. The trial used the Amyvid and Tauvid PET scans to enroll patients with confirmed amyloid plaques, allowing investigators to confirm clearance or reduction of the pathology in later scans.

Among all patients, treatment with donanemab reduced amyloid plaque on average by 84% at 18 months, compared with a 1% decrease for patients taking placebo.

Patients were able to stop taking donanemab once they achieved pre-defined criteria of amyloid plaque clearance. About half of patients met this threshold at 12 months and about seven of every 10 participants reached this threshold at 18 months.