Modified Dosing Regimen of Eli Lilly’s Alzheimer’s Drug Kisunla (Donanemab) Reduces Brain Swelling

Modified Dosing Regimen:
A modified dosing regimen of Eli Lilly's Alzheimer's drug Kisunla (donanemab) has shown a significant reduction in amyloid-related imaging abnormalities with oedema/effusion (ARIA-E), a form of brain swelling.

TRAILBLAZER-ALZ 6 Trial:
The TRAILBLAZER-ALZ 6 Phase IIIb trial evaluated the impact of different dosing regimens of Kisunla on ARIA-E and amyloid clearance in adults with early symptomatic Alzheimer’s disease. The trial included four treatment arms, with one arm using the standard dosing regimen and three arms using alternative dosing regimens.

Reduction in ARIA-E:
The modified titration resulted in a 41% lower relative risk of ARIA-E compared to the standard dosing regimen. Specifically, the incidence of ARIA-E was 14% in patients receiving the modified titration versus 24% for those receiving the standard dosing regimen.

Impact on APOE4 Homozygotes:
The largest ARIA-E reduction with the modified titration was seen in apolipoprotein E (APOE4) homozygotes, with a 67% lower relative risk. In these patients, 19% had ARIA-E on the modified titration compared to 57% on the standard dosing regimen.

Amyloid Plaque Removal:
The modified titration showed comparable reduction in amyloid plaque and P-tau217 levels to the standard dosing regimen, with an average reduction of 67% from baseline compared to 69% for the standard dosing regimen.

Regulatory Submission:
Eli Lilly intends to submit these results to global regulators for a potential label update for Kisunla.