Efficacy and safety of donanemab in the European eligible population: TRAILBLAZER-ALZ 2 post-hoc analyses.

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The Journal of Prevention of Alzheimer's Disease Pub Date : 2026-10-01 Epub Date: 2026-05-27 DOI:10.1016/j.tjpad.2026.100605

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

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引用次数: 0

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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donanemab在欧洲符合条件人群中的有效性和安全性：TRAILBLAZER-ALZ 2事后分析

背景：在欧盟，donanemab适用于载脂蛋白E ε4非携带者或杂合子的早期症状性阿尔茨海默病成人患者。其中，基线时无浅表性铁沉着、高血压未控制或使用抗凝剂的患者符合条件。目的：评价donanemab在符合欧盟条件人群中的有效性和安全性。方法：在TRAILBLAZER-ALZ 2安慰剂对照期，采用事后保守混合法进行临床疗效分析。在78周的长期延长（LTE）中，早期开始组（随机分配到多纳耐单抗组）和延迟开始组（随机分配到多纳耐单抗起始的安慰剂组）的参与者与倾向加权外部对照进行比较。在满足以淀粉样蛋白为基础的疗程完成标准后，参与者被换成安慰剂。结果：到76周时，在符合欧盟条件的人群中，接受donanemumab治疗的参与者的平均临床痴呆评分量表(CDR)-箱变和基线与安慰剂的差异为-0.7点（95%置信区间，-1.0,-0.4），疾病进展到下一阶段的风险降低了40.3%（按CDR- global评分）。非携带者和杂合子的治疗效果在154周后增加，包括那些在52周或76周达到疗程完成标准的患者。在安慰剂对照期，分别有119名（19.5%）和49名（8.0%）donanemab治疗的符合条件的参与者经历了淀粉样蛋白相关的影像学异常——水肿/积水和输注相关反应。在安慰剂对照期和LTE延迟启动组中，donanemab治疗的参与者的安全性发现相似。结论：与先前的TRAILBLAZER-ALZ 2和LTE研究结果一致，与非携带者和杂合子相比，donanemab显著减缓了疾病进展，具有可控的安全性。

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来源期刊

The Journal of Prevention of Alzheimer's Disease Medicine-Psychiatry and Mental Health

CiteScore

9.20

自引率

0.00%

发文量

期刊介绍： The JPAD Journal of Prevention of Alzheimer’Disease will publish reviews, original research articles and short reports to improve our knowledge in the field of Alzheimer prevention including: neurosciences, biomarkers, imaging, epidemiology, public health, physical cognitive exercise, nutrition, risk and protective factors, drug development, trials design, and heath economic outcomes.JPAD will publish also the meeting abstracts from Clinical Trial on Alzheimer Disease (CTAD) and will be distributed both in paper and online version worldwide.We hope that JPAD with your contribution will play a role in the development of Alzheimer prevention.