Enhanced Kisunla Dosing Regimen Reduced ARIA-E Risk While Maintaining Amyloid Reduction in Early Alzheimer Disease

Results from the multicenter, randomized, double-blind, phase 3b TRAILBLAZER-ALZ 6 (NCT05738486) clinical trial revealed that an enhanced dosing regimen for Kisunla (donanemab; Eli Lilly and Company, Indianapolis, IN) significantly reduces the frequency and severity of amyloid-related imaging abnormalities with edema/effusion (ARIA-E) at 24 weeks compared to the standard dosing regimen used in the phase 3 TRAILBLAZER-ALZ 2 (NCT04437511) trial. 

Study participants (n=843) were stratified by apolipoprotein E (APOE) genotype and baseline amyloid levels and were divided equally into 1 of 4 once-monthly treatment arms: the standard dosing regimen or 3 alternative dosing regimens. Infusion dosages varied across the 4 treatment arms, but the total exposure to Kisunla was the same for all by week 16. 

One of the alternative dosing arms, the enhanced dosing regimen, reduced the frequency of ARIA-E from 27.3% in the standard dosing arm to 13.7%, a 41% reduction in relative risk. This enhanced dosing arm also significantly reduced the severity of ARIA-E; mild, moderate, and severe cases dropped from 9.2 to 4.7%, 12.6 to 9.0%, and 1.9 to 0%, respectively. Participants in both the standard and enhanced dosing arms saw a significant amyloid reduction from baseline at 24 weeks: 58.8 Centiloids in the standard dosing arm, and 56.3 Centiloids in the enhanced dosing arm

Researchers, who announced their results at the 17th annual Clinical Trials on Alzheimer’s Disease (CTAD) conference, say their study suggests that the new enhanced dosing regimen can lower ARIA risk while maintaining sufficient amyloid reduction. 

Complete results from the TRAILBLAZER-ALZ 6 trial are expected in 2025.