Donanemab/Kisunla Approved to Treat Early Alzheimer Disease

The Food and Drug Administration (FDA) has approved Kisunla (donanemab-azbt; Eli Lilly and Company, Indianapolis, IN) as a once-monthly injection for intravenous (IV) infusion to treat adults with early symptomatic Alzheimer disease (AD) and confirmed amyloid pathology, including people with mild cognitive impairment (MCI) and the mild dementia stage of AD. This approval follows the unanimous vote by the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee in June 2024 about the clinical benefits of Kisunla treatment in people with early AD.

The approval is based on data from the phase 3 TRAILBLAZER-ALZ 2 clinical trial (NCT04437511), which evaluated the safety and efficacy of Kisunla in individuals aged 60 to 85 years with early symptomatic AD. The randomized, double-blind, placebo-controlled study enrolled 1736 participants from 8 countries who demonstrated a broad range of amyloid levels and cognitive scores at baseline. Participants were stratified by tau score into a low-medium tau group (n=1182) and a high tau group (n=552) and were then assessed for function and cognition on the integrated Alzheimer’s Disease Rating Scale (iADRS) over 18 months as a primary endpoint.

Individuals who were treated with Kisunla in the low-medium tau group showed a significant slowing of decline of 35% on the iADRS, and the treatment response in the overall population was 22%. Across both groups, individuals treated with Kisunla showed a 39% lower risk of progressing to the next clinical stage of AD as compared with those receiving placebo.

Additionally, treatment with Kisunla was associated with significant reductions in amyloid plaque levels as measured by PET.

• At 6 months, amyloid plaques were reduced by an average of 61%.
• At 12 months, an average of 80%.
• At 18 months, an average of 84%.

In TRAILBLAZER-ALZ 2, participants treated with Kisunla who showed minimal levels of amyloid plaque as assessed by a visually negative amyloid PET scan at 6, 12, or 18 months were switched to placebo. This makes Kisunla the first and only amyloid-targeting therapy with evidence supporting the cessation of therapy upon removal of amyloid plaques, lowering treatment costs and the number of required infusions. Kisunla’s label contains a 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." said Howard Fillit, MD, Co-Founder and Chief Science Officer at the Alzheimer's Drug Discovery Foundation (ADDF).