Eli Lilly and Company has announced a significant positive development for patients with early symptomatic Alzheimer's disease: the U.S. Food and Drug Administration (FDA) has approved an updated label for its once-monthly amyloid-targeting therapy, Kisunla (donanemab-azbt). This updated label introduces a new, more gradual titration dosing schedule designed to enhance patient safety. The approval is based on compelling data from the TRAILBLAZER-ALZ 6 study, which specifically investigated different dosing regimens.

The key finding from this study, which underpins the label change, is that the modified titration schedule significantly lowered the incidence of amyloid-related imaging abnormalities with edema/effusion (ARIA-E). ARIA-E is a known side effect of amyloid plaque-targeting therapies, often appearing as temporary swelling in the brain, though serious and even fatal events can occur. The TRAILBLAZER-ALZ 6 study demonstrated a 41% lower relative risk of ARIA-E by week 24 and a 35% lower relative risk by week 52 with the new dosing, compared to the original schedule.

Crucially, this substantial reduction in ARIA-E risk did not compromise Kisunla's therapeutic effectiveness. Patients on the modified titration regimen experienced comparable levels of amyloid plaque removal and P-tau217 reduction as those on the original schedule. This means that Kisunla retains its ability to significantly slow cognitive and functional decline, as established by the TRAILBLAZER-ALZ 2 Phase 3 trial data, which led to its initial FDA approval in July 2024. That trial showed Kisunla slowed decline by up to 35% in less pathologically advanced patients and by 22% in the overall study population, while also reducing the risk of progressing to the next clinical stage of disease by 37% over 18 months.

The new dosing recommendation subtly shifts a single vial from the first dose to the third dose, delivering the same total amount of Kisunla by week 24. This adjustment allows for a more gentle introduction of the therapy, contributing to a more favorable safety profile. According to Dr. Brandy Matthews, Lilly's Vice President of Global & US Medical Affairs for Alzheimer's Disease, this update underscores Lilly's "unwavering commitment to patient safety and the advancement of Alzheimer's disease treatment." The modified dosing strategy is considered a meaningful advancement for patients and their care teams, offering greater confidence in the safety of Kisunla while preserving its ability to effectively reduce amyloid plaque. Lilly also continues to offer comprehensive patient support services for Kisunla, including coverage assistance and nurse navigator support, to assist patients throughout their treatment journey.