JAMA NetworkDonanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial

Is donanemab, a monoclonal antibody designed to remove brain amyloid plaque, clinically beneficial in the early stages of Alzheimer’s disease?

In a comprehensive phase 3 trial carried out across 277 medical research centers and hospitals in eight countries, researchers sought to assess the efficacy of donanemab, a monoclonal antibody designed to clear brain amyloid plaque, in patients with early symptomatic Alzheimer disease. The robust double-blind, placebo-controlled trial included 1,736 participants and aimed to investigate how donanemab might provide clinical benefits to this specific population.

Study Design:

• Setting: Multicenter trial, conducted in 277 research centers/hospitals across eight countries
• Type: Randomized, double-blind, placebo-controlled, 18-month phase 3 trial
• Participants: 1,736 individuals with early symptomatic Alzheimer disease (mild cognitive impairment/mild dementia), amyloid and tau pathology, average age 73.0 years
• Intervention: 1:1 ratio of donanemab (n=860) or placebo (n=876) intravenously every 4 weeks for 72 weeks
• Completion: 1,320 (76%) completed the trial
• Timeline: June 2020 to November 2021 (last patient visit for primary outcome in April 2023)

Key Findings:

• Primary Outcome: Significant difference in least-squares mean change in integrated Alzheimer Disease Rating Scale (iADRS) score at 76 weeks; −6.02 for donanemab group vs. −9.27 in placebo group for low/medium tau population, and −10.19 vs. −13.11 for the combined population
• Secondary Outcome: Significant difference in LSM change in Clinical Dementia Rating Scale (CDR-SB) score at 76 weeks
• Adverse Events: Amyloid-related imaging abnormalities in 24.0% of donanemab group, infusion-related reactions in 8.7% of the donanemab group, 3 treatment-related deaths in the donanemab group, and 1 in the placebo group

Conclusion:

• Donanemab treatment significantly slowed clinical progression at 76 weeks among participants with early symptomatic Alzheimer disease and amyloid and tau pathology, indicating potential as a treatment option for this population.

Related Link

• Association of Amyloid Reduction After Donanemab Treatment with Tau Pathology and Clinical Outcomes: The TRAILBLAZER-ALZ Randomized Clinical Trial

Did You Know?
Alzheimer’s disease is the 6th leading cause of death in the United States, and as of now, there are limited efficacious treatments available for it.