Describe clinical efficacy and safety of donanemab in early start (ES) and delayed start (DS) participants during the TRAILBLAZER-ALZ 2 placebo-controlled (PC) trial and blinded long-term extension (LTE).

TRAILBLAZER-ALZ 2 (NCT04437511), a Phase 3 trial, assessed the efficacy and safety of donanemab in participants with early symptomatic Alzheimer’s disease (AD). Donanemab treatment significantly slowed clinical progression in the 76-week PC period. Participants that completed the period were eligible for a 78-week double-blind LTE.

ES participants were randomized to donanemab in the PC period. DS participants (randomized to placebo in the PC period) started donanemab in the LTE. ES and DS participants switched to placebo based on amyloid level criteria during any study period. Participants from Alzheimer’s Disease Neuroimaging Initiative (ADNI) were external control groups and weighted to match key demographics and characteristics for TRAILBLAZER-ALZ 2 at study entry/baseline. All analyses were exploratory.

During the LTE, the ES group continued to separate from their external ADNI control group on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) with a difference of -1.2 (95% CI: -1.7,-0.7) at 3 years. The DS group showed a difference of -0.8 (95% CI: -1.3,-0.3) on the CDR-SB compared to their respective ADNI control group 76 weeks after starting donanemab. The ES group showed a significantly lower risk of progression to the next clinical disease stage over 3 years (HR=0.73; p<0.001). In both groups, >75% of participants assessed by PET 76 weeks after starting donanemab achieved amyloid clearance (<24.1 Centiloids) and amyloid plaque reaccumulation was 2.4 Centiloids/year. No new safety signals were observed.