Kisunla: A Promising Step Forward in Alzheimer’s Treatment

Savarimuthu Sherly

Alzheimer’s disease is the most predominant type of neurological disorder that causes disability and mortality worldwide, yet has no cure. Alzheimer’s is characterized by beta-amyloid plaques and neurofibrillary tau tangles in the brain(1) . These changes occur years before the patients begin to show symptoms, which solidifies the importance of early intervention in delaying disease progression. In the past, certain disease-modifying treatments have failed to demonstrate clinical significance due to late intervention by neurologists, often when the disease has already caused significant deterioration in the patient’s activities of daily living (1). Early intervention has shown to significantly decrease the impact of the disease, such as neuron loss and irreversible brain damage (2,4). Newer treatments, such as anti-amyloid immunotherapies, are FDA-approved to treat the cause of the disease along with the symptoms in its early stages. Kisunla (donanemab) is a monoclonal antibody immunotherapy that selectively binds to beta-amyloid plaques, rather than soluble amyloid forms, in the brain, facilitating their clearance and consequently allowing people to participate in their daily activities and take control of their lives (1,3). 

Who took part-and Why it Matters 

The phase 3 TRAILBLAZER-ALZ 2 randomized control trial (RCT) evaluated the efficacy of Kisunla in 1736 participants, of whom 996 are women and 740 are men across 8 countries, who had early symptomatic Alzheimer's disease and beta-amyloid plaques as confirmed by PET imaging (3). The participants were randomized into the Kisunla group (treatment) or placebo group (control) and received once-monthly IV infusions for up to 18 months (3). The participants were analyzed in two groups, with one group who were in the early stages of the diseases (low to

medium tau levels) and another group which included the overall population (high tau levels) (3). The level of plaque formation was measured using amyloid PET imaging and participants were switched to the placebo group if the plaque levels reached below the threshold (3). The Integrated Alzheimer’s Disease Rating Scale (iADRS) is a clinical assessment used by researchers to measure participants' thinking ability and daily living. This assessment was used to determine whether Kisunla slowed the progression of the disease compared to the placebo (3). 

A Closer Look at Safety 

Like any medication, Kisunla comes with risks. The most common adverse effects were infusion-related reactions and amyloid-related imaging abnormalities (ARIA), which included brain swelling and small bleeds that occurred more often in the donanemab than the placebo group (3). It is also worth noting that 3 participants in the donanemab group subsequently died as a result of ARIA due to 2 of the participants carrying the ApoE ε4 homozygote allele that predisposes them to having Alzheimer’s disease (3). 

Key Findings from the Trial 

They found that the participants in Kisunla group had slowed clinical progression of the disease over a period of 18 months and less chance of the disease progressing to the next stage than those that were in the placebo group (3). The participants who were less advanced in their disease showed a slower decline of 35% in their cognitive function as compared to the placebo group which was measured using iADRS (3). Kisunla reduced amyloid plaque formation in the brain as shown in 66% of the participants at 52 weeks and in 76% of the participants at 76 weeks (3). In simpler terms, the participants' thinking and everyday functioning declined more slowly than if they had not received any treatment. Patients were more likely to have reduced plaque formation if treatment with Kisunla was initiated in the early stages of the disease as opposed to later stages. 

Looking Ahead 

Kisunla shows a promising start to treating the cause of the disease as compared to just treating the symptoms. Kisunla does not cure or treat the disease -rather it appears to slow down the cognitive decline, especially when administered in the early stages of the disease over 3 years. This study also emphasizes the need to start early detection, intervention and treatment of Alzheimer’s disease. More research is needed to refine the dosing protocols, balance effectiveness with safety and to determine how long these benefits last. For those affected by Alzheimer’s, there is a growing need to assess the importance of developing novel drug therapies specifically tailored to treat early-stage Alzheimer’s disease and to bring us closer to better options.

References 

1. Alzheimer's Association. (2025). What Is Alzheimer’s Disease? Alzheimer’s Association. https://www.alz.org/alzheimers-dementia/what-is-alzheimers 

2. Jack, C. R., Jr, Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., Liu, E., Molinuevo, J. L., Montine, T., Phelps, C., Rankin, K. P., Rowe, C. C., Scheltens, P., Siemers, E., Snyder, H. M., Sperling, R., … Contributors (2018). NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association, 14(4), 535–562. https://doi.org/10.1016/j.jalz.2018.02.018 

3. Sims, J. R., Zimmer, J. A., Evans, C. D., Lu, M., Ardayfio, P., Sparks, J., Wessels, A. M., Shcherbinin, S., Wang, H., Monkul Nery, E. S., Collins, E. C., Solomon, P., Salloway, S., Apostolova, L. G., Hansson, O., Ritchie, C., Brooks, D. A., Mintun, M., Skovronsky, D. M., & TRAILBLAZER-ALZ 2 Investigators (2023). Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA, 330(6), 512–527. https://doi.org/10.1001/jama.2023.13239 

4. Sperling, R. A., Rentz, D. M., Johnson, K. A., Karlawish, J., Donohue, M., Salmon, D. P., & Aisen, P. (2014). The A4 study: stopping AD before symptoms begin?. Science translational medicine, 6(228), 228fs13. https://doi.org/10.1126/scitranslmed.3007941 

5. George J. FDA Approves Label Change for Alzheimer’s Amyloid Drug [Internet]. MedPage Today. MedpageToday; 2025 [cited 2026 Jun 18]. Available from: https://www.medpagetoday.com/neurology/alzheimersdisease/116438 (Source for figure)

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