FDA Grants Donanemab Breakthrough Therapy Status for Alzheimer Disease

The Food and Drug Administration (FDA) granted breakthrough therapy designation for donanemab (LY3002813; Eli Lilly, Indianapolis, IN) investigational antibody therapy for Alzheimer disease (AD). The breakthrough therapy designation will expedite the development and review of donanemab, which is an investigational treatment intended to treat AD. 

Donanemab is a humanized monoclonal antibody that targets the N3pG form of amyloid β In the phase 2 TRAILBLAZER-ALZ study (NCT03367403), 40% of individuals with early symptomatic AD treated with donanemab had amyloid negativity after 6 months of treatment, and this rose to 68% afterfter 18 months of treatment. Overall, those treated with donanemab had approximately an 85 centiloid reduction in amyloid plaque compared with those treated with placebo. Results of the TRAILBLAZER-ALZ study have been published in The New England Journal of Medicine.

A biologics license application (BLA) for donanemab treatment of AD is planned for submission to the FDA under the expedited approval pathway, based on data from TRAILBLAZER-ALZ study. Donanemab safety, tolerability, and efficacy are also being evaluated in a phase 3 study TRAILBLAZER-ALZ 2 (NCT04437511). 

In TRAINLBLAZER-ALZ, 272 participants had cognitive assessments in conjunction with amyloid plaque imaging and tau staging by PET imaging. Effects of treatment were measured as change from baseline until 76 weeks on the Integrated Alzheimer's Disease Rating Scale (iADRS), a composite tool combining the Alzheimer Disease Assessment Scale-Cognitive subscale (ADAS-Cog13) and the Alzheimer Disease Cooperative Study—instrumental Activities of Daily Living (ADCS-iADL) for function.