Donanemab in early symptomatic Alzheimer’s disease: results from the TRAILBLAZER-ALZ 2 long-term extension - 02/12/25

Doi : 10.1016/j.tjpad.2025.100446

Jennifer A. Zimmer, John R. Sims ^⁎ , Cynthia D. Evans, Emel Serap Monkul Nery, Hong Wang, Alette M. Wessels, Giulia Tronchin, Shoichiro Sato, Lars Lau Raket, Scott W. Andersen, Christophe Sapin, Marie-Ange Paget, Ivelina Gueorguieva, Paul Ardayfio, Rashna Khanna, Dawn A. Brooks, Brandy R. Matthews, Mark A. Mintun
for the
Alzheimer’s Disease Neuroimaging Initiative ^†
Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: ADNI_Acknowledgement_List.pdf

Eli Lilly and Company, Indianapolis, IN, USA

^⁎ Corresponding author at, Lilly Corporate Center, Indianapolis, IN 46285, USA. Lilly Corporate Center Indianapolis IN 46285 USA

connectez-vous ou créez un compte

Bienvenue sur EM-consulte, la référence des professionnels de santé.
Article gratuit.

Connectez-vous pour en bénéficier!

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Tuesday 02 December 2025

Highlights

•	Donanemab-treated participants showed increasing clinical benefits over 3 years.
•	Clinical benefits of donanemab continued after the treatment course was completed.
•	Amyloid reaccumulation was comparable to the natural amyloid accumulation rate.
•	No new safety signals were seen versus the established safety profile of donanemab.

Le texte complet de cet article est disponible en PDF.

Abstract

Background

Donanemab significantly slowed clinical progression in participants with early symptomatic Alzheimer’s disease (AD) during the 76-week placebo-controlled period of TRAILBLAZER-ALZ 2.

Methods

Participants who completed the placebo-controlled period were eligible for the 78-week, double-blind, long-term extension (LTE). Early-start participants were randomized to donanemab in the placebo-controlled period. Delayed-start participants (randomized to placebo) started donanemab in the LTE. Participants who met amyloid treatment course completion criteria were switched to placebo. An external control cohort comprised participants from the AD Neuroimaging Initiative (ADNI).

Results

At 3 years, donanemab slowed disease progression on the Clinical Dementia Rating Scale (CDR)-Sum of Boxes (CDR-SB) in early-start participants versus a weighted ADNI control (-1.2 points; 95 % confidence interval [CI], -1.7, -0.7). Seventy-six weeks after initiating donanemab, delayed-start participants also demonstrated slower CDR-SB progression versus a weighted ADNI control (-0.8 points; 95 % CI, -1.3, -0.3). Participants who completed treatment by 52 weeks demonstrated similar slowing of CDR-SB progression at 3 years. Compared with delayed-start participants, early-start participants demonstrated a significantly lower risk of disease progression on the CDR-Global over 3 years (hazard ratio=0.73; p < 0.001). In both groups, >75 % of participants assessed by positron emission tomography 76 weeks after starting donanemab achieved amyloid clearance (<24.1 Centiloids). The addition of LTE data to prior modeling predicted a median reaccumulation rate of 2.4 Centiloids/year. No new safety signals were observed compared to the established donanemab safety profile.

Conclusions

Over 3 years, donanemab-treated participants with early symptomatic AD demonstrated increasing clinical benefits and a consistent safety profile, with limited-duration dosing.