Practical NeurologyDonanemab/Kisunla Approved to Treat Early Alzheimer Disease

Donanemab Targets Amyloid Plaques in Early Alzheimer’s, Offering New Treatment Paradigm

The FDA has approved Kisunla (donanemab-azbt) for the treatment of early symptomatic Alzheimer’s disease (AD) with confirmed amyloid pathology. This once-monthly intravenous infusion, developed by Eli Lilly and Company, has demonstrated significant efficacy in slowing cognitive decline and reducing amyloid plaque levels in patients with mild cognitive impairment and mild dementia stages of AD.

Key Points:

• Kisunla is approved for adults with early symptomatic AD and confirmed amyloid pathology
• Treatment is administered via once-monthly intravenous infusion
• Approval based on phase 3 TRAILBLAZER-ALZ 2 clinical trial results
• Study enrolled 1736 participants aged 60-85 years from 8 countries
• Participants stratified into low-medium tau (n=1182) and high tau (n=552) groups
• Primary endpoint: assessment of function and cognition using iADRS over 18 months
• Low-medium tau group showed 35% slowing of decline on iADRS
• Overall population demonstrated 22% slowing of decline
• 39% lower risk of progressing to next clinical AD stage across both groups
• Significant reductions in amyloid plaque levels:
  • 61% average reduction at 6 months
  • 80% average reduction at 12 months
  • 84% average reduction at 18 months
• First amyloid-targeting therapy allowing cessation upon plaque removal
• Patients switched to placebo after achieving minimal amyloid plaque levels
• Label contains Boxed Warning for amyloid-related imaging abnormalities (ARIA)

“This approval marks another step forward in evolving the standard of care for people living with Alzheimer’s disease that will ultimately include an arsenal of novel treatments, providing much needed hope to the Alzheimer’s community.”
– Howard Fillit, MD, Co-Founder and Chief Science Officer at the Alzheimer’s Drug Discovery Foundation (ADDF)

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