The Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Eli Lilly regarding the application for accelerated approval for donanemab, an investigational therapy for early symptomatic Alzheimer disease.

Donanemab is an antibody therapy that targets a modified form of deposited amyloid-β peptide called N3pG. The accelerated approval application was based on data from the phase 2 TRAILBLAZER-ALZ trial (ClinicalTrials.gov Identifier: NCT03367403), which evaluated the efficacy and safety of donanemab in patients with early symptomatic Alzheimer disease who had tau and amyloid deposition.

Due to the limited number of patients with 12-month drug exposure data provided in the submission, the Agency could not move forward with its review and issued the CRL requesting that data be provided for at least 100 patients who received a minimum of 12 months of continued treatment. According to the Company, the trial did include more than 100 patients; however, many stopped treatment as early as 6 months due to the speed of plaque reduction. This resulted in fewer than 100 patients receiving treatment for a 12-month period.

A confirmatory trial, the phase 3 TRAILBLAZER-ALZ 2 study (ClinicalTrials.gov Identifier: NCT04437511), is ongoing and will form the basis of the submission for traditional approval. The Company expects topline data from this trial in the second quarter of 2023.

“We look forward to our upcoming confirmatory TRAILBLAZER-ALZ 2 phase 3 results and subsequent FDA submission, which we’ve always seen as the most impactful next steps for patients,” said Anne White, executive vice president and president of Lilly Neuroscience, Eli Lilly and Company. “We anticipate this study will confirm the benefit and safety profile we observed in the TRAILBLAZER-ALZ phase 2 study and believe that patients and physicians will be well served by having the full phase 3 data available alongside our phase 2 data when they need to make treatment decisions.”

Reference

US Food and Drug Administration issues Complete Response Letter for accelerated approval of donanemab. News release. Accessed January 20, 2023. https://www.prnewswire.com/news-releases/us-food-and-drug-administration-issues-complete-response-letter-for-accelerated-approval-of-donanemab-301726325.html.