Efficacy and safety of donanemab in the European eligible population: TRAILBLAZER-ALZ 2 post-hoc analyses
- 1Department of Psychiatry, Medical Faculty, University of Cologne, Cologne, Germany; German Center for Neurodegenerative Diseases, Bonn, Germany; Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany
- 2Eli Lilly and Company, Indianapolis, IN, USA
- 3Unit of Neurology and Neuroimaging of Neurodegenerative Diseases, IRCCS Ospedale San Raffaele, Milano, Italy; "Vita-Salute San Raffaele" University, Milano, Italy
Abstract
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.
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BibTeX
@article{jessen2026efficacy,
title = {{Efficacy and safety of donanemab in the European eligible population: TRAILBLAZER-ALZ 2 post-hoc analyses}},
author = {Frank Jessen and Grazia Dell’Agnello and Jennifer A. Zimmer and Christophe Sapin and Sascha Dichter and Erin Gautier Doty and Stéphane Epelbaum and Cynthia Duggan Evans and Paula M. Hauck and Rashna Khanna and Dawn A. Brooks and John Randall Sims and Federica Agosta},
journal = {The Journal of Prevention of Alzheimer s Disease},
year = {2026},
month = may,
doi = {10.1016/j.tjpad.2026.100605},
url = {https://doi.org/10.1016/j.tjpad.2026.100605},
note = {CC BY},
}
RIS
TY - JOUR
TI - Efficacy and safety of donanemab in the European eligible population: TRAILBLAZER-ALZ 2 post-hoc analyses
AU - Frank Jessen
AU - Grazia Dell’Agnello
AU - Jennifer A. Zimmer
AU - Christophe Sapin
AU - Sascha Dichter
AU - Erin Gautier Doty
AU - Stéphane Epelbaum
AU - Cynthia Duggan Evans
AU - Paula M. Hauck
AU - Rashna Khanna
AU - Dawn A. Brooks
AU - John Randall Sims
AU - Federica Agosta
PY - 2026
DA - 2026/05/27
JO - The Journal of Prevention of Alzheimer s Disease
DO - 10.1016/j.tjpad.2026.100605
UR - https://doi.org/10.1016/j.tjpad.2026.100605
AB - 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.
SN - 2274-5807
SN - 2426-0266
ER -