Donanemab Label Revised: New Dosing Schedule Approved for Early Alzheimer’s Treatment

The US Food and Drug Administration (FDA) has approved a revised label for donanemab-azbt (Kisunla, Eli Lilly), updating the recommended dosing schedule for adults with early symptomatic Alzheimer disease (AD). The modified titration regimen demonstrated a significantly lower incidence of amyloid-related imaging abnormalities with edema or effusion (ARIA-E), a known adverse effect of amyloid-targeting therapies, compared to the original schedule.¹

Donanemab is indicated for once-monthly intravenous treatment in adults with mild cognitive impairment or mild dementia stage of AD, confirmed by amyloid pathology. The updated schedule, based on findings from the Phase 3b TRAILBLAZER-ALZ 6 study, shifts one vial from the first dose to the third dose while maintaining the total dose by week 24. This adjustment resulted in a 41% reduction in ARIA-E incidence at 24 weeks (14% vs 24%) and a 35% reduction at 52 weeks (16% vs 25%) compared with the original dosing schedule.¹

Importantly, the modified dosing did not compromise the treatment’s efficacy. Individuals receiving the updated regimen experienced comparable reductions in amyloid plaque and plasma P-tau217 levels to those on the original schedule, with average amyloid plaque reduction at 24 weeks reaching 67% vs 69%, respectively.¹

No new adverse events were identified. However, rates of hypersensitivity and infusion-related reactions were higher with the modified regimen. ARIA, including ARIA-E and ARIA-H (hemosiderin deposition), was observed in 29% of patients at week 52.¹

Donanemab received FDA approval in July 2024 based on TRAILBLAZER-ALZ-2 results, which showed up to a 35% reduction in cognitive and functional decline in patients with less advanced disease over 18 months compared with placebo. It also reduced progression to the next clinical disease stage by 37%.²

The updated label aims to improve the safety profile of donanemab while maintaining therapeutic efficacy, offering clinicians a refined treatment approach for eligible patients with early Alzheimer disease.¹

References:

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

2. Halsey G. Lilly's donanemab approved by FDA for treatment of early symptomatic AD. Patient Care Online. July 2, 2024. https://www.patientcareonline.com/view/lilly-s-donanemab-approved-by-fda-for-treatment-of-early-symptomatic-ad