FDA Declines to Give Accelerated Approval of Donanemab in Early Symptomatic Alzheimer Disease

The FDA has declined to give accelerated approval of donanemab, Eli Lilly’s investigational therapy for early symptomatic Alzheimer disease, the company announced yesterday.¹

The complete response letter was based on the FDA’s desire to see data on more patients with a full year’s exposure to the drug; no other deficiencies were reported. According to the statement from Eli Lilly, a readout of phase 3 data from the TRAILBLAZER-ALZ 2 trial and submission based on traditional timelines remain on track for midyear 2023.

According to the statement, the FDA requested that Lilly provide data from at least 100 patients who received a minimum of 12 months of continued treatment with donanemab, a monoclonal antibody that targets a form of amyloid-β exclusively found in plaques. Donanemab’s ability to target the plaque allowed for the unique design of TRAILBLAZER-ALZ, which let patients complete treatment once they reached a predefined level of plaque clearance.

More than 100 patients were enrolled in the phase 2 TRAILBLAZER-ALZ trial. However, because the plaque cleared quickly, many patients were able to stop taking the drug after just 6 months, leading to fewer than 100 patients taking it for a full year. The statement from Lilly says, in part, “The FDA indicated that the data to meet the exposure expectation would likely need to include the unblinded controlled safety data from TRAILBLAZER-ALZ 2 upon completion.”

Safety data were first reported in the New England Journal of Medicine in 2021 and have remained consistent, according to Lilly officials.²

References

1. US Food and Drug Administration issues complete response letter for accelerated approval of donanemab. News release. Eli Lilly and Company. January 19, 2023. Accessed January 20, 2023. https://investor.lilly.com/news-releases/news-release-details/us-food-and-drug-administration-issues-complete-response-0
2. Mintun M, Lo A, Evans C, et al. Donanemab in early Alzheimer's disease. N Engl J Med. 2021;384(18):1691-1704. doi: 10.1056/NEJMoa2100708.