Donanemab Slows Rate of Cognitive Decline in Early Symptomatic Alzheimer Disease 

In the phase 2 TRAILBLAZER-ALZ (NCT03367403) study, donanemab (LY3002813; Lilly and Company, Indianapolis, IN) reduced cognitive decline in individuals with early symptomatic Alzheimer disease (AD) compared with placebo. Cognitive decline was measured with the Integrated AD Rating Scale (iADRS) and was slowed by 32% over 76 weeks in those treated with donanemab vs placebo. Donanemab treatment resulted in consistent improvements of cognition and function compared with placebo, although not all improvements reached statistical significance. 

Donanemab is thought to act on cognitive decline by reducing amyloid plaques in the brain, measured as centiloids on amyloid imaging. Over 76 weeks, participants treated with donanemab had a mean 77% reduction of amyloid plaque from a baseline mean 108 centiloids. Individuals who had less than 25 centiloids of amyloid plaque for 2 consecutive measures or less than 11 centiloids at any 1 measurement were switched to placebo treatment. 

TRAILBLAZER-ALZ was a randomized placebo-controlled double-blind multicenter phase 2 study to assess the safety, tolerability, and efficacy of donanemab. The trial enrolled 272 participants with early symptomatic AD based on cognitive assessments in conjunction with amyloid plaque imaging and tau imaging. Donanemab is also being evaluated in a larger phase 2 study TRAILBLAZER-ALZ 2 (NCT04437511). 

The safety profile of donanemab was consistent with observations from phase 1 data, which included amyloid-related imaging abnormalities (ARIA) consistent with amyloid plaque-clearing antibodies. In those treated with donanemab, ARIA with edema (ARIA-E) occurred in 27% with an overall incidence of 6% experiencing symptomatic ARIA-E.