INDIANAPOLIS, July 9, 2025 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) announced today that the U.S. Food and Drug Administration (FDA) has approved a label update with a new recommended titration dosing schedule for Kisunla (donanemab-azbt), Lilly's once-monthly amyloid-targeting therapy for adults with early symptomatic Alzheimer's disease (AD), which includes people with mild cognitive impairment (MCI) as well as people in the mild dementia stage of AD, with confirmed amyloid pathology.1,2 In the TRAILBLAZER-ALZ 6 study, the modified titration schedule significantly lowered the incidence of amyloid-related imaging abnormalities with edema/effusion (ARIA-E) versus the original dosing schedule at 24 and 52 weeks, while still achieving similar levels of amyloid plaque removal and P-tau217 reduction.
"We are confident that this label update for Kisunla will significantly aid healthcare professionals in evaluating appropriate treatment options for their patients," stated Brandy Matthews, MD, FAAN, Lilly's Vice President of Global & US Medical Affairs for Alzheimer's Disease. "This update underscores our unwavering commitment to patient safety and the advancement of Alzheimer's disease treatment by potentially mitigating the risk of ARIA-E."
The new recommended dosing regimen involves a more gradual titration, and the TRAILBLAZER-ALZ 6 study significantly lowered the incidence of ARIA-E by 41% at 24 weeks and by 35% at 52 weeks versus the original dosing schedule. ARIA-E is a side effect of amyloid plaque-targeting therapies, including Kisunla. ARIA-E is usually asymptomatic, although serious and fatal events can occur. The new dosing recommendation differs from the original dosing by shifting a single vial from the first dose to the third dose, delivering the same amount of Kisunla by week 24. This resulted in lower rates of ARIA-E without compromising Kisunla's ability to reduce amyloid plaque or Kisunla's once-monthly dosing with the potential for limited-duration treatment based on amyloid plaque removal to minimal levels.3-6
Key findings from the TRAILBLAZER-ALZ 6 study, which supports this label update, included:
-
The primary endpoint of the study was the proportion of participants with any occurrence of ARIA-E by week 24. The results showed the incidence of ARIA-E was 14% in patients receiving the modified titration compared with 24% for those receiving the original dosing regimen, a 41% lower relative risk.7 At week 52, the incidence of ARIA-E was 16% in patients receiving the modified titration compared with 25% for those receiving the original dosing regimen, a 35% lower relative risk.
-
Including asymptomatic radiographic events at week 52, ARIA, ARIA-E, and ARIA-H were observed in 29%, 16%, and 25% of patients receiving the modified titration dosing. ARIA-E and ARIA-H are different types of amyloid-related imaging abnormalities (ARIA). ARIA with edema is characterized as ARIA-E and ARIA with hemosiderin deposition is characterized as ARIA-H.
-
Patients on the modified titration experienced a reduction of amyloid plaque and P-tau217 comparable to patients receiving the original dosing regimen. As observed using amyloid PET at the primary endpoint of 24 weeks, amyloid plaque levels in patients on the modified titration of donanemab in TRAILBLAZER-ALZ 6 were reduced on average 67% from baseline compared to 69% for patients on the original dosing regimen.7,8
-
No new adverse reactions were identified in this study, although higher rates of hypersensitivity reactions and infusion-related reactions were observed.
"This updated dosing strategy is a meaningful advancement for patients and their care teams," said Elly Lee, MD, Chief Medical Officer and Principal Investigator, Irvine Center for Clinical Research. "By significantly reducing the risk of ARIA-E, we can offer patients and care teams greater confidence in the safety of Kisunla while preserving its ability to reduce amyloid."
The U.S. FDA approved Kisunla in July 2024 based on the TRAILBLAZER-ALZ 2 Phase 3 clinical trial data. The study demonstrated that Kisunla significantly slowed cognitive and functional decline in patients who were less pathologically advanced in their disease by up to 35% and by 22% in the overall study population compared to placebo at 18 months.9 Kisunla reduced the risk of progressing to the next clinical stage of disease by 37% over the same period.3 Cognitive and functional decline was characterized by more severe memory and thinking problems, more trouble with daily activities, and a greater need for help from caregivers.3,10
Please see the INDICATION AND SAFETY SUMMARY WITH WARNINGS below.
Lilly Support Services for Kisunla is dedicated to assisting patients throughout their treatment journey with Kisunla. This free program provides essential services, including coverage determination assistance, care coordination, nurse navigator support, and personalized resources. For more information about Lilly Support Services and Kisunla, visit www.kisunla.lilly.com or call 1-800-LillyRx (1-800-545-5979).
About Kisunla™ (donanemab)
Kisunla™ (donanemab-azbt) (pronounced kih-SUHN-lah) is an amyloid-targeting therapy for people with mild cognitive impairment (MCI) as well as people with mild dementia stage of early symptomatic Alzheimer's disease, with confirmed amyloid pathology. Kisunla (donanemab-azbt) injection for intravenous use is available as a 350 mg/20 mL single-dose vial. Kisunla can cause serious side effects, including amyloid-related imaging abnormalities, or ARIA, and infusion-related reactions.
About TRAILBLAZER-ALZ 6 study and the TRAILBLAZER-ALZ program
TRAILBLAZER-ALZ 6 (NCT05738486) is a Phase 3b, multicenter, randomized, double-blind study to investigate different dosing regimens and their effect on ARIA-E in adults with early symptomatic Alzheimer's disease. The trial enrolled 843 participants ages 60-85 selected based on cognitive assessments in conjunction with amyloid plaque imaging by PET scan.7 These study results were published in Alzheimer's and Dementia.
About TRAILBLAZER-ALZ 2 study
TRAILBLAZER-ALZ 2 (NCT04437511) is a Phase 3, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of donanemab in participants with early symptomatic Alzheimer's disease (MCI or mild dementia due to Alzheimer's disease) with the presence of confirmed Alzheimer's disease neuropathology. The trial enrolled 1,736 participants, across 8 countries, selected based on cognitive assessments in conjunction with evidence of Alzheimer's disease pathology. The Phase 3 TRAILBLAZER-ALZ 2 study results were published in the Journal of the American Medical Association (JAMA).
Lilly continues to study donanemab in multiple clinical trials, including TRAILBLAZER-ALZ 3, evaluating the potential to reduce the risk of progression to symptomatic AD in participants with preclinical AD; and TRAILBLAZER-ALZ 5, a registration trial for early symptomatic AD currently enrolling in China, Korea, Taiwan, and other geographies.
About Lilly
Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable.
References
-
Kisunla (donanemab-azbt). Prescribing Information. Lilly USA, LLC.
-
Kisunla (donanemab-azbt). Medication Guide. Lilly USA, LLC.
-
Sims JR, Zimmer JA, Evans CD, et al. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA. 2023;330(6):512-527. doi:10.1001/jama.2023.13239.
-
Ross EL, Weinberg MS, Arnold SE. Cost-effectiveness of Aducanumab and Donanemab for Early Alzheimer Disease in the US. JAMA Neurol. 2022;79(5):478-487. doi:10.1001/jamaneurol.2022.0315.
-
Boustani M, Doty EG, Garrison LP Jr, et al. Assessing the Cost-effectiveness of a Hypothetical Disease-modifying Therapy With Limited Duration for the Treatment of Early Symptomatic Alzheimer Disease. Clin Ther. 2022;44(11):1449-1462. doi:10.1016/j.clinthera.2022.09.008.
-
Mattke S, Ozawa T and Hanson M. Implications of Treatment Duration and Intensity on the Value of Alzheimer's Treatments. Clinical Trials on Alzheimer's Disease. Oct. 24-27, 2023.
-
Wang H, Monkul Nery ES, Ardayfio P, et al. (2025). 21(4). https://doi.org/10.1002/alz.70062
-
Data on File. Lilly USA, LLC. DOF-DN-US-0069.
-
Data on File. Lilly USA, LLC. DOF-DN-US-0053.
-
2024 Alzheimer's disease facts and figures. Alzheimers Dement. 2024 May;20(5):3708-3821. doi: 10.1002/alz.13809. Epub 2024 Apr 30. PMID: 38689398; PMCID: PMC11095490.