Donanemab: FDA Advisors Unanimously Recommend for Approval

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A panel of US Food and Drug Administration (FDA) advisors unanimously recommended Eli Lilly’s donanemab to treat Alzheimer disease, marking the next step towards potential full FDA approval later this year.¹

In an initial vote, 11 panel members unanimously said that he available donanemab data shows that it is effective at treating the early stages of Alzheimer disease. However, several panel members noted the need for more data in minoritized groups, such as Black and Hispanic patients. Furthermore, the panel agreed that donanemab’s benefits outweigh its risks.

While the FDA is not required to follow the recommendation of its advisory committee, it usually does.

“Today’s vote offers hope that donanemab will be approved in the coming months, but it’s important to look at this milestone in the larger treatment landscape for Alzheimer’s, which will entail a combination therapy and precision medicine approach,” says Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation (ADDF). “If approved, donanemab will expand the first class of disease-modifying drugs, serving as the building blocks for future generations of drugs. Anti-amyloids are not a silver bullet, but they offer opportunities for patients to modify the course of the disease while the field works towards developing more novel therapies that target the underlying biology.”²

“There’s a huge unmet medical need here that hopefully can be addressed,” said committee member Sarah Dolan, a consultant for the non-profit organization Critical Path Institute.¹

Earlier this year, the FDA delayed a potential decision on donanemab last minute, and called this meeting to evaluate the phase 3 Trailblazer-Alz 2 trial in order to “further understand topics related to evaluating the safety and efficacy of donanemab.”³ The FDA initially rejected the drug in January 2023 due to insufficient data, so this delay came as another unpleasant surprise for Eli Lilly.

“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,” said Anne White, executive vice president of Eli Lilly and Company, and president of Lilly Neuroscience.³

Trailblazer-Alz 2 is a phase 3, double-blind, placebo-controlled study that 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.

This positive news also follows the rather recent negative updates for other Alzheimer disease treatments: 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 BIIB113.⁴ However, lecanemab continues to struggle to pick up speed on the market, with only 2000 patients receiving the drug.⁵

It is important to note that the FDA advisors do believe donanemab will come with a strong boxed warning that shares the risks of brain swelling and bleeding, as 24% of trial participants who took donanemab experienced brain swelling and 31% experienced brain bleeding.¹

“Today’s advisory committee endorsement is a milestone achievement for the researchers, patients, families, and caregivers who have dedicated years to advancing new treatment options, but our work does not end here. We must continue fostering innovation and progress to move closer to the day where Alzheimer’s is treated on an individual basis with the help of precision medicine, ultimately halting the progression or preventing the onset of the disease altogether,” said Fillit.

References

1. Constantino AK. FDA advisors recommend Eli Lilly’s Alzheimer’s drug donanemab, paving way for approval. CNBC. May 10, 2024. Accessed May 10, 2024. https://www.cnbc.com/2024/06/10/fda-advisors-recommend-eli-lilly-alzheimers-drug-donanemab.html

2. ADFF statement on FDA Advisory Committee's endorsement of donanemab. Alzheimer's Drug Discovery Foundation. June 10, 2024. Accessed June 10, 2024. https://www.alzdiscovery.org/news-room/announcements/addf-statement-on-fda-advisory-committees-endorsement-of-donanemab

3. 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

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

5. 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/