Alzheimer’s Antibody Therapy from Eli Lilly Granted US FDA Breakthrough Therapy designation

Donanemab, Eli Lilly and Company’s investigational antibody therapy for Alzheimer's disease (AD), has received Breakthrough Therapy designation from the US Food and Drug Administration (FDA). The Breakthrough Therapy designation is based on clinical evidence for donanemab, an investigational antibody that targets a modified form of beta amyloid called N3pG. The company's Phase 2 trial, TRAILBLAZER-ALZ, studied the efficacy and safety of donanemab in patients with early, symptomatic AD. These data were presented at the 15th International Conference on Alzheimer's & Parkinson Diseases™ 2021 (AD/PD™ 2021) and published in the New England Journal of Medicine.

Lilly intends to submit a biologics license application (BLA) for donanemab under the accelerated approval pathway later this year based on data from TRAILBLAZER-ALZ. The safety, tolerability and efficacy of donanemab are also being evaluated in the ongoing randomized, placebo-controlled, double-blind, multi-center Phase 3 study TRAILBLAZER-ALZ 2 (NCT04437511). 

TRAILBLAZER-ALZ is a randomized, placebo-controlled, double-blind, multi-center Phase 2 study to assess the safety, tolerability and efficacy of donanemab in patients with early symptomatic Alzheimer's disease. The trial enrolled 272 patients who were selected based on cognitive assessments in conjunction with amyloid plaque imaging and tau staging by PET imaging. The study's primary endpoint was change from baseline until 76 weeks in the Integrated Alzheimer's Disease Rating Scale (iADRS), a composite tool combining the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog13) and the Alzheimer's Disease Cooperative Study - instrumental Activities of Daily Living (ADCS-iADL) for function. Key secondary endpoints included changes between baseline and 76 weeks in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13), ADCS-iADL, MMSE, and Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores. Other secondary biomarker endpoints included changes from baseline to week 76 in brain amyloid deposition and brain tau deposition and volumetric MRI.