FDA issues Complete Response Letter for accelerated approval of donanemab for treatment of early symptomatic Alzheimer's disease

The confirmatory Phase III TRAILBLAZER-ALZ 2 trial remains ongoing, with topline data read-out expected in Q2 2023, and will form the basis of donanemab's application for traditional approval shortly thereafter. Lilly will continue to work with the FDA to evaluate the fastest pathway to make this potential treatment option widely available to patients.

In the complete response letter to the accelerated approval application, the FDA specifically requested that Lilly provide data from at least 100 patients who received a minimum of 12 months of continued treatment on donanemab. Donanemab's specificity to target deposited amyloid plaque informed the unique clinical trial design of TRAILBLAZER-ALZ, which allowed patients to complete their course of treatment when they reached a predefined level of amyloid plaque clearance. While the trial included more than 100 patients treated with donanemab, due to the speed of plaque reduction, many patients were able to stop dosing as early as 6 months of treatment, resulting in fewer than 100 patients receiving 12 months of donanemab. 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.

The safety profile of donanemab was initially reported from the TRAILBLAZER-ALZ trial in the New England Journal of Medicine (Mintun et al, NEJM 2021)(previously cited). The safety profile of donanemab has remained consistent since the accelerated approval submission.