Lilly’s Kisunla Demonstrates Growing Benefit in Treating Early Alzheimer’s Disease

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Eli Lilly and Company (Lilly) announced on July 30, 2025 results from a long-term extension (LTE) of a Phase III study (TRAILBLAZER-ALZ 2), which showed that participants treated with donanemab-azbt (brand name Kisunla) demonstrated slowing of decline (1)—a benefit that continued to grow over a span of three years, compared to an untreated external cohort from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (2). Under the brand name Kisunla, donanemab-azbt was approved by FDA in July 2024 for treating Alzheimer’s disease (AD) (3).

Participants in the Phase III study who began treatment at a later time still saw benefit; however, study participants who started treatment earlier significantly reduced the risk of progression to the next stage of AD compared to those who received treatment later (2). Data from the study were presented at the 2025 Alzheimer's Association International Conference (AAIC) in Toronto, Canada, which occurred on July 27–30.

"The TRAILBLAZER-ALZ 2 long-term extension reaffirms that Kisunla delivered sustained clinical benefit that continued to increase over three years and a consistent safety profile," said Mark Mintun, MD, group vice-president, Neuroscience Research & Development, Eli Lilly and Company, in a company press release (1). "Participants continued to show meaningful outcomes, reinforcing the long-term value of early intervention."

Phase III LTE study findings

This Phase III LTE study (TRAILBLAZER-ALZ 2 LTE) was a double-blind extension of the original Phase III clinical trial (TRAILBLAZER-ALZ 2) designed to evaluate the efficacy and safety of donanemab-azbt in individuals with early symptomatic AD (2). Participants originally treated with donanemab-azbt were either continued on the same treatment or were switched to placebo, while those initially on placebo began treatment with donanemab-azbt in a blinded manner. To assess outcomes against a matched, untreated population, an external comparator group from ADNI was used.

The key preliminary results from the LTE study include:

• The demonstration that the donanemab-azbt benefit continued to grow over the course of three years in study participants treated with the therapy compared to those in the matched ADNI group. The data show that donanemab-azbt reduced cognitive decline by -0.6 at 18 months and -1.2 at 36 months based on the Clinical Dementia Rating Sum of Boxes (CDR-SB). These data came from patients initially treated with the therapy in the core study compared to the ADNI group.
• An earlier start of treatment with donanemab-azbt reduced the risk of disease progression to the next stage by 27% on the Clinical Dementia Rating-Global Score (CDR-G) compared to the group who had delayed initiation of treatment.
• More than 75% of participants treated with donanemab-azbt achieved amyloid clearance within 76 weeks from the start of treatment.
• Observed data gathered after up to 2.5 years in participants who had completed treatment showed that the reaccumulation of amyloid plaque remained slow at a rate of approximately 2.4 CL/year, which was consistent with prior observations and modeling.
• No new safety signals were observed in the study over the three-year period, which supports the established safety profile for donanemab-azbt.

Side effects include amyloid-related imaging abnormalities (ARIA) with edema/effusion (ARIA-E) and with hemorrhage/with hemosiderin deposition. These are side effects within the class of amyloid targeting therapies that do not usually cause any symptoms; however, serious and life-threatening symptoms can occur. ARIA can be fatal, according to Lilly in the release.

References

1. Eli Lilly and Co. Lilly’s Kisunla (donanemab-azbt) Showed Growing Benefit Over Three Years in Early Symptomatic Alzheimer’s Disease. Press Release. July 30, 2025.
2. National Library of Medicine. A Study of Donanemab (LY3002813) in Participants with Early Alzheimer's Disease (TRAILBLAZER-ALZ 2). ClinicalTrials.gov, May 4, 2025 (accessed Aug. 5, 2025).
3. FDA. FDA Roundup: July 2, 2024. Press Announcement. July 2, 2024.