Analyzing Subgroup Data From the TRAILBLAZER-ALZ 2 Study of Donanemab: Brandy Matthews, MD

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"In the long-term extension, we saw that participants who initiated donanemab in the original placebo-controlled study had a 27% reduced risk of advancing to the next stage of disease compared to those who initiated donanemab in the long-term extension portion of the study."

The TRAILBLAZER-ALZ 2 study (NCT04437511) is a multicenter, randomized, double-blind, placebo-controlled phase 3 trial assessing the efficacy and safety of donanemab (Kisulna; Eli Lilly) among patients with early symptomatic Alzheimer disease (AD). In previously reported findings, donanemab treatment significantly slowed clinical progression in participants at 76 weeks in the placebo-controlled period. Participants who completed this period were then eligible to continue into the long-term extension period, lasting an additional 78 weeks.¹

Over a 3-year treatment period, newly presented results showed that participants on donenamab demonstrated a slowing of disease progression on the Clinical Dementia Rating Scale-Sum of Boxes compared with an untreated external cohort from the Alzheimer's Disease Neuroimaging Initiative. In addition, researchers also observed no new safety signals compared with the established donanemab safety profile. These findings were recently presented at the 18th Clinical Trials on Alzheimer’s Disease (CTAD) Conference, held December 1-4, 2025, in San Diego, California, by lead author Jennifer Zimmer, MD, associate vice president of clinical research at Eli Lily and Company.²

At the conference, NeurologyLive^® caught up with coauthor Brandy Matthews, MD, vice president of U.S. medical affairs and global for Alzheimer's Disease at Eli Lilly and Company, who discussed the secondary analyses of the TRAILBLAZER-ALZ 2 long-term extension study, focusing on a subgroup patients who completed 12 months of donanemab therapy. She noted that these patients demonstrated persistent cognitive and functional benefits, along with sustained amyloid clearance, for 2 years following the end of treatment. In addition, she talked about how no new safety signals emerged, and that the rate of amyloid-related imaging abnormalities remained consistent with those initially on placebo.

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REFERENCES
1. Zimmer JA, Sims JR, Evans CD, et al. Donanemab in early symptomatic Alzheimer's disease: results from the TRAILBLAZER-ALZ 2 long-term extension. J Prev Alzheimers Dis. Published online December 1, 2025. doi:10.1016/j.tjpad.2025.100446
2. Zimmer J. Donanemab in Early Symptomatic Alzheimer’s Disease: Additional Insights from the TRAILBLAZER-ALZ 2 Long-Term Extension. Presented at: 2025 Clinical Trials on Alzheimer Disease conference. December 1-5; San Diego, CA. Abstract OC21.