Donanemab-Azbt Demonstrated Long-Term Efficacy in Slowing Cognitive Decline

In the multicenter, randomized, double-blind, placebo-controlled, long-term extension (LTE) of the phase 3 TRAILBLAZER‐ALZ 2 (NCT04437511), donanemab-azbt (Kisunla; Eli Lilly and Company) demonstrated a continued slowing of cognitive decline over 3 years. The study authors found that the effect was even more pronounced when compared with an untreated group of patients from a separate study called the Alzheimer Disease Neuroimaging Initiative (ADNI).¹

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"The TRAILBLAZER-ALZ 2 long-term extension reaffirms that [donanemab-azbt] delivered sustained clinical benefit that continued to increase over three years and a consistent safety profile," Mark Mintun, MD, group vice president, Neuroscience Research & Development, Eli Lilly and Company, said in a news release. "Participants continued to show meaningful outcomes, reinforcing the long-term value of early intervention."

Symptoms and Signs of Alzheimer Disease

Alzheimer disease (AD) is triggered by a buildup of proteins in the form of amyloid plaques and neurofibrillary tangles in the brain, causing brain cells to die over time and the brain to shrink. In the United States, nearly 6.9 million individuals ages 65 years and older live with AD, and of the more than 55 million individuals with dementia globally, 60% to 70% are predicted to have AD, according to Mayo Clinic.²

Memory loss and difficulty reflecting on recent events or conversations are the first signs of AD, which individuals can recognize and be aware of. However, as the disease progresses, memory loss can worsen and could impact an individual’s daily life. This includes changes in personality and behavior, loss of interest in activities, social withdrawal, mood swings, not trusting others, anger or aggression, changes in sleeping habits, wandering, loss of inhibitions, and delusions.²

TRAILBLAZER-ALZ 2 LTE Study

Following the initial 76-week, placebo-controlled phase of the TRAILBLAZER-ALZ 2 study, which evaluated the efficacy and safety of donanemab-azbt in individuals with early symptomatic AD, eligible participants were able to continue to a long-term extension period. This extension lasted an additional 78 weeks and remained blinded to both the participants and the investigators.¹

In the main study, a total of 550 individuals initially treated with donanemab-azbt either continued treatment in the LTE or were switched to placebo if they met the pre-defined amyloid clearance thresholds. Individuals that received placebo in the main study were switched to donanemab-azbt in the LTE to assess delayed treatment outcomes. A total of 657 individuals in the delayed start group received donanemab-azbt in the same dosing, administration, and stopping measures as the main study.¹

The results demonstrated that treatment with donanemab-azbt showed an increased benefit over 3 years, slowing cognitive decline when compared with a matched group from the ADNI study. Specifically, donanemab-azbt reduced cognitive decline by a score of -0.6 at 18 months and -1.2 at 36 months on the Clinical Dementia Rating Sum of Boxes (CDR-SB) scale. Starting treatment with donanemab-azbt earlier also reduced the risk of progressing to the next stage of the disease by 27% compared with a group that delayed their treatment.¹

Further results revealed that more than 75% of individuals achieved amyloid clearance within 76 weeks. After completing treatment, the rate of amyloid plaque reaccumulation was slow, consistent with previous results. Furthermore, the study authors noted that there were no new safety concerns identified over the 3-year period.¹

The findings suggest the importance of early intervention for AD and support a limited dosing approach with continued benefits.¹

REFERENCES

1. Lilly's Kisunla (donanemab-azbt) showed growing benefit over three years in early symptomatic Alzheimer's disease. Eli Lilly and Company. News release. July 30, 2025. Accessed August 5, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-kisunla-donanemab-azbt-showed-growing-benefit-over-three

2. Alzheimer’s Disease. Mayo Clinic. News release. November 8, 2024. Accessed August 5, 2025. https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/symptoms-causes/syc-20350447