Aims

Donanemab is an antibody targeting a modified form of Aβ called N3pG. This study aimed to assess the potential treatment effects of donanemab on disease progression in individuals with early symptomatic Alzheimer’s Disease (AD).

Methods

TRAILBLAZER-ALZ (NCT03367403) was a randomized, placebo-controlled, double-blind, multi-center Phase 2 study assessing the safety, tolerability and efficacy of donanemab in patients with early symptomatic AD. The trial enrolled 272 patients, selected based on cognitive assessments in conjunction with amyloid and tau positron emission tomography (PET). The primary efficacy endpoint was change from baseline to 76 weeks in the Integrated AD Rating Scale (iADRS), a composite tool combining the AD Assessment Scale-Cognitive subscale (ADAS-Cog13) and the AD Cooperative Study - instrumental Activities of Daily Living (ADCS-iADL) for function. Secondary endpoints included changes in CDR-SB, ADAS-Cog13, ADCS-iADL, MMSE, amyloid PET, tau PET, and volumetric MRI.

Results

Donanemab significantly slowed the clinical decline compared to placebo on the primary outcome, iADRS, by 32%. On average, patients who received donanemab showed an 84 centiloid reduction of amyloid plaque at 76 weeks. In the donanemab treatment group, amyloid-related imaging abnormalities – edema (ARIA-E) occurred in 27% of treated participants. Secondary and exploratory outcome measures will be presented.

Conclusions