Donanemab Delay: FDA Calls for Last-Minute Meeting to Discuss Safety and Efficacy

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Alzheimer disease treatment donanemab will be delayed past the end of March as the US Food and Drug Administration (FDA) plans to convene a meeting of the Peripheral and Central Nervous System Drugs Advisory Committee to evaluate the phase 3 Trailblazer-Alz 2 trial and “further understand topics related to evaluating the safety and efficacy of donanemab.”¹ The meeting date has not yet been set.

“We are confident in donanemab’s potential to offer very meaningful benefits to people with early symptomatic Alzheimer’s disease,” said Anne White, executive vice president of Eli Lilly and Company, and president of Lilly Neuroscience. “It was unexpected to learn the FDA will convene an advisory committee at this stage in the review process, but we look forward to the opportunity to further present the Trailblazer-Alz 2 results and put donanemab’s strong efficacy in the context of safety.”¹

Trailblazer-Alz 2—a phase 3, double-blind, placebo-controlled study—evaluated the safety and efficacy of donanemab in participants aged 60 to 85 years with early symptomatic Alzheimer disease. Investigators enrolled 1736 participants across 8 countries, who were selected based on cognitive assessments along with amyloid plaque imaging and tau staging by PET imaging. Compared with participants in similar trials of other amyloid plaque-targeting therapies, the Trailblazer-Alz 2 participants were more progressed in their disease.

Unlike other treatments for Alzheimer disease, the unique trial design of the donanemab study allows patients to stop receiving treatment upon clearing of the amyloid plaques from their brain. The FDA seeks to evaluate this difference.

Donanemab’s key risk is amyloid related imaging abnormalities, a potentially life-threatening issue. In the phase 3 clinical trial, 37% of participants experienced ARIA, and 3 deaths occurred.² Other commonly reported adverse effects include infusion-related reactions, headache, and nausea.

This serves as another setback for treatments centered on Alzheimer disease. Donanemab was expected to be approved last year, following in the footsteps of aducanumab and lecanemab. Aducanumab was discontinued in January by Biogen, and the company intends to focus efforts on lecanemab with partners Eisai, along with other pipeline modalities like BIIB080 and BIIB113.³ However, lecanemab continues to struggle to pick up speed on the market, with only 2000 patients receiving the drug.⁴

References

1. U.S. Food and Drug Administration to convene advisory committee meeting to discuss the TRAILBLAZER-ALZ 2 study of donanemab. Eli Lilly. News release. March 8, 2024. https://investor.lilly.com/news-releases/news-release-details/us-food-and-drug-administration-convene-advisory-committee

2. Sims JR, Zimmer JA, Evans CD, et al. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA. 2023;330(6):512-527.

3. Kuntz L. Biogen discontinues aducanumab for Alzheimer disease. Psychiatric Times. January 31, 2024. https://www.psychiatrictimes.com/view/biogen-discontinues-aducanumab-for-alzheimer-disease

4. Bell J. Eisai falls behind on Leqembi patient goal. Bio Pharma Dive. February 6, 2024. Accessed March 8, 2024. https://www.biopharmadive.com/news/eisai-leqembi-alzheimers-target-revenue-earnings/706668/