journal articles
EFFICACY AND SAFETY OF DONANEMAB IN THE EUROPEAN ELIGIBLE POPULATION: TRAILBLAZER-ALZ 2 POST-HOC ANALYSES
Frank Jessen, Grazia Dell’Agnello, Jennifer A. Zimmer, Christophe Sapin, Sascha Dichter, Erin Doty, Stéphane Epelbaum, Cynthia D. Evans, Paula M. Hauck, Rashna Khanna, Dawn A. Brooks, John R. Sims, Federica Agosta
BACKGROUND: In the European Union (EU), donanemab is indicated in adults with early symptomatic Alzheimer’s disease who are apolipoprotein E ε4 non-carriers or heterozygotes. Among these, patients without superficial siderosis at baseline, uncontrolled hypertension, or anticoagulant use are eligible.
OBJECTIVE: To assess efficacy and safety of donanemab in the EU-eligible population.
METHODS: A post-hoc conservative hybrid imputation method was implemented for clinical efficacy analyses during the TRAILBLAZER-ALZ 2 placebo-controlled period. In the 78-week long-term extension (LTE) participants in the early-start (randomised to donanemab) and delayed-start (randomised to placebo with donanemab initiation during the LTE) groups were compared to a propensity-weighted external control. Participants were switched to placebo after meeting amyloid-based treatment course completion criteria.
RESULTS: By 76 weeks, donanemab-treated participants in the EU-eligible population had a mean Clinical Dementia Rating Scale (CDR)-Sum of Boxes change from baseline difference from placebo of -0.7 points (95% confidence interval, -1.0, -0.4) and a 40.3% lower risk of disease progression to the next stage (per CDR-Global score). Treatment benefit increased over 154 weeks for non-carriers and heterozygotes, including those meeting treatment course completion criteria by 52 or 76 weeks. In the placebo-controlled period, 119 (19.5%) and 49 (8.0%) donanemab-treated eligible participants experienced amyloid-related imaging abnormalities-edema/effusion and infusion-related reactions, respectively. Safety findings were similar among donanemab-treated participants in the placebo-controlled period and LTE delayed-start group.
CONCLUSIONS: Consistent with previous TRAILBLAZER-ALZ 2 and LTE findings, donanemab significantly slowed disease progression compared to controls with a manageable safety profile in non-carriers and heterozygotes.
CITATION:
Frank Jessen ; Grazia Dell’Agnello ; Jennifer A. Zimmer ; Christophe Sapin ; Sascha Dichter ; Erin Doty ; Stéphane Epelbaum ; Cynthia D. Evans ; Paula M. Hauck ; Rashna Khanna ; Dawn A. Brooks ; John R. Sims ; Federica Agosta ; Alzheimer’s Disease Neuroimaging Initiative (ADNI) (2025): Efficacy and safety of donanemab in the European eligible population: TRAILBLAZER-ALZ 2 post-hoc analyses. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100605