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On July 30, 2025, we reported on study findings presented at the 2025 Alzheimer’s Association International Conference (AAIC) that examined the efficacy and safety of donanemab in individuals with early symptomatic Alzheimer disease.
The study
Researchers presented data from the long-term extension (LTE) of the phase 3 TRAILBLAZER-ALZ 2 clinical trial. The original study included 1736 participants aged 60-85 years received donanemab (n = 860) or placebo (n = 876) administered intravenously every 4 weeks for up to 72 weeks. The LTE study enrolled 1207 participants who had completed the 76-week TRAILBLAZER-ALZ-2 study.
Participants in the LTE study were grouped based on original assignment and followed for an additional 78 weeks. Those who received donanemab (n=550) either continued therapy or were switched to placebo after reaching positron emission tomography (PET)-confirmed amyloid clearance thresholds. Participants initially assigned to placebo (n=657) were crossed over to donanemab at LTE entry and followed under the same dosing and stopping criteria.
The primary efficacy outcome was the change from baseline in the Clinical Dementia Rating–Sum of Boxes (CDR-SB), with additional assessments including the Clinical Dementia Rating–Global Score (CDR-G) and amyloid plaque burden by PET.
The findings
At 36 months, the donanemab-treated group had a –1.2 point difference in CDR-SB compared to a matched untreated external cohort from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). This benefit grew from a –0.6 point difference at 18 months, indicating continued slowing of cognitive and functional decline over time. In analyses of disease progression, early initiation of donanemab was associated with a 27% lower risk of progressing to the next stage of AD, based on CDR-G scoring, compared with delayed treatment initiation.
Amyloid plaque reduction was robust. More than 75% of participants who received donanemab achieved PET-confirmed amyloid clearance within 76 weeks of treatment. Among participants who had stopped therapy and were followed for up to 2.5 years, amyloid reaccumulation occurred at a slow rate of approximately 2.4 Centiloids per year—consistent with previous modeling.
