The Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to donanemab for the treatment of Alzheimer disease.
Donanemab is an investigational antibody therapy that targets a modified form of deposited amyloid-β peptide called N3pG. The designation is based on data from the phase 2 TRAILBLAZER-ALZ trial (ClinicalTrials.gov Identifier: NCT03367403), which evaluated the efficacy and safety of donanemab in 257 patients with early symptomatic Alzheimer disease who had tau and amyloid deposition. Patients were randomly assigned 1:1 to receive donanemab or placebo intravenously every 4 weeks for up to 72 weeks.
Findings showed that treatment with donanemab led to less decline based on change from baseline on the Integrated Alzheimer Disease Rating Scale (-6.86 vs -10.06 for placebo; difference, 3.20; 95% CI, 0.12-6.27; P =.04), a composite tool combining the Alzheimer Disease Assessment Scale-Cognitive subscale and the Alzheimer Disease Cooperative Study – Instrumental Activities of Daily Living for function. No substantial differences were observed for most secondary outcomes including scores for dementia, cognition, daily living, and mental state.
The Company plans to submit a Biologics License Application (BLA) for donanemab under the accelerated approval pathway later this year. Donanemab is currently being investigated in the ongoing multicenter, randomized, double-blind, placebo-controlled phase 3 TRAILBLAZER-ALZ 2 trial (ClinicalTrials.gov Identifier: NCT04437511) for early Alzheimer disease.
- Lilly’s donanemab receives U.S. FDA’s Breakthrough Therapy designation for treatment of Alzheimer’s disease. [press release]. Indianapolis, IN: Eli Lilly and Company; June 24, 2021.
- Mintun MA, Lo AC, Evans CD, et al. Donanemab in Early Alzheimer’s Disease. N Engl J Med. Published online May 6, 2021. doi: 10.1056/NEJMoa2100708.