Full Results from TRAILBLAZER-ALZ 2 Demonstrate Donanemab Effective at Slowing Cognitive and Functional Decline in Early Alzheimer Disease

The full results of the phase 3 TRAILBLAZER-ALZ 2 (NCT04437511) study were presented at the 2023 meeting of the Alzheimer’s Association International Conference (AAIC), showing that treatment with donanemab (Eli Lilly and Company, Indianapolis, IN) in patients with early symptomatic Alzheimer disease (AD) significantly slowed functional and cognitive decline, especially for younger patients with early stage of disease at baseline. The findings were simultaneously published in the Journal of the American Medical Association. Eli Lilly previously announced positive results from TRAILBLAZER-ALZ 2 showing that donanemab met all primary and secondary endpoints, and the company subsequently submitted the drug to the US Food and Drug Administration (FDA) for traditional approval. The new announcement also reveals that donanemab’s benefit increases over time.

TRAILBLAZER-ALZ 2, a randomized, double-blind, placebo-controlled study, included 1736 participants with a broad range of amyloid levels and cognitive scores at baseline. Participants were stratified by tau score into a low-medium tau (n=1182) group and a high tau group (n=552) and were then assessed for function and cognition on the integrated Alzheimer’s Disease Rating Scale (iADRS) and the Clinical Dementia Rating-Sum of Boxes (CDR-SB) over 18 months. Patients with the earlier disease stage of mild cognitive impairment, compared to those with mild dementia from AD, showed greater reductions in decline on the iADRS (60% vs 30%) and CDR-SB (46% vs 38%). Additionally, patients aged younger than 75 years, compared to those aged 75 years and older, showed greater reductions in decline on the iADRS (48% vs 25%) and CDR-SB (45% vs 29%). The results were consistent across other subgroups, including in those with the APOE ε4 allele, and the benefits of treatment increased over time and were greatest at 18 months.

“This is the first Phase 3 study of a disease-modifying therapy to replicate the positive clinical results observed in a previous study", said Anne White, Executive Vice President of Eli Lilly and Company and President of Lilly Neuroscience.

Donanemab is an antibody that targets amyloid beta (Aβ), an abnormal protein associated with AD. Regulatory action is expected from the FDA by the end of the year.