Donanemab-Azbt Receives FDA Label Update With New Dosing for Alzheimer Disease

The FDA has approved an updated label with a new recommended titration dosing schedule for donanemab-azbt (Kisunla; Eli Lilly and Company) for once-monthly amyloid-targeting therapy for adults that experience early symptomatic Alzheimer disease (AD). The therapy is also indicated for individuals with mild cognitive impairment and individuals in the mild dementia stage of AD with confirmed amyloid pathology. The recommendation includes a new, more gradual dosing schedule for donanemab that significantly reduces the incidence of abnormalities with edema/effusion (ARIA-E).¹

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"We are confident that this label update for [donanemab] will significantly aid health care professionals in evaluating appropriate treatment options for their patients," Brandy Matthews, MD, FAAN, Lilly's vice president of global and US medical affairs for AD, said in a news release.¹

Donanemab-Azbt for AD

AD is marked as the most common cause of dementia, impacting nearly 6.9 million individuals in the United States aged 65 and older. The disease is caused by a buildup of proteins in the form of amyloid plaques and neurofibrillary tangles in the brain that causes brain cells to die and leads to brain shrinking. The beginning signs and symptoms for Alzheimer includes forgetting recent events or conversations, which could later progress to serious memory loss and an inability to complete daily tasks.²

While there is no cure for the disease, medications could improve symptoms or slow the decline. As an amyloid-targeting therapy, donanemab is indicated to slow cognitive and functional decline in individuals who are less pathologically advanced in their disease.^1,2

New Recommendation Based on TRAILBLAZER-ALZ Clinical Trials

The updated label change for donanemab is based on the TRAILBLAZER-ALZ 6 study (NCT05738486), which showed that this modified regimen lowered ARIA-E rates by 41% at 24 weeks and 35% at 52 weeks compared with the original schedule. Although ARIA-E is typically asymptomatic, severe and fatal cases have occurred. The updated dosing shifts a single vial from the first dose to the third, maintaining the same total amount of donanemab by week 24. The researchers noted that this adjustment effectively mitigates ARIA-E without negatively impacting donanemab’s efficacy in reducing amyloid plaque or its convenient once-monthly dosing, which offers the potential for a limited-duration treatment once plaque levels are minimized.¹

Further results from the trial demonstrated that individuals receiving the modified donanemab titration regimen experienced comparable reductions in amyloid plaque and P-tau217 levels to those on the original dosing schedule. At 24 weeks, amyloid PET scans showed that individuals on the modified titration of donanemab had an average 67% reduction seen in amyloid from baseline, closely matching the 69% reduction seen in individuals on the original regimen. While no new adverse reactions were observed in this study, higher rates of hypersensitivity and infusion-related reactions were observed.¹

"This updated dosing strategy is a meaningful advancement for patients and their care teams," Elly Lee, MD, chief medical officer and principal investigator, Irvine Center for Clinical Research, said in the news release. "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."¹

Previous FDA Approval For Donanemab-Azbt

In July 2024, the FDA approved donanemab for the treatment of early symptomatic AD based on data from the TRAILBLAZER-ALZ 2 (NCT04437511), which assessed its safety and efficacy. A total of 1736 individuals across 8 countries were included, demonstrating slowed clinical progression at 76 weeks. The initial approval marked donanemab as the first and only amyloid plaque-targeting therapy that supports stopping therapy when the plaque is removed.³

REFERENCES

1. FDA approves updated label for Lilly's Kisunla (donanemab-azbt) with new dosing in early symptomatic Alzheimer's disease. Eli Lilly and Company. News release. July 9, 2025. Accessed July 9, 2025. https://www.prnewswire.com/news-releases/fda-approves-updated-label-for-lillys-kisunla-donanemab-azbt-with-new-dosing-in-early-symptomatic-alzheimers-disease-302500615.html

2. Mayo Clinic. Alzheimer’s Disease. News release. November 8, 2024. Accessed July 9, 2025. https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/symptoms-causes/syc-20350447

Gallagher A. FDA Approves Donanemab-Azbt for Early Symptomatic Alzheimer Disease. Pharmacy Times. July 2, 2024. Accessed July 9, 2025. https://www.pharmacytimes.com/view/fda-approves-donanemab-azbt-for-early-symptomatic-alzheimer-disease