Eli Lilly and Company has announced that the U.S. Food and Drug Administration (FDA) has approved a label update for Kisunla (donanemab-azbt), its once-monthly amyloid-targeting therapy for early symptomatic Alzheimer’s disease. The update introduces a revised titration dosing schedule designed to lower the risk of a known side effect—amyloid-related imaging abnormalities with edema/effusion (ARIA-E)—without compromising the drug’s efficacy.
Kisunla is indicated for patients with confirmed amyloid pathology who are in the mild cognitive impairment (MCI) or mild dementia stages of Alzheimer’s disease. The updated label is based on findings from the Phase 3 TRAILBLAZER-ALZ 6 study, which demonstrated that the modified titration schedule significantly reduced the risk of ARIA-E by 41% at 24 weeks and by 35% at 52 weeks compared to the original dosing regimen.
The revised regimen involves a more gradual titration by shifting one vial from the first to the third dose while delivering the same total dosage by week 24. This change maintained Kisunla’s once-monthly schedule and did not affect its ability to reduce amyloid plaque or P-tau217 levels—two key biomarkers associated with Alzheimer’s progression.
In the study, patients receiving the modified dosing had a 14% incidence of ARIA-E by week 24, compared to 24% with the original schedule. At week 52, the incidence was 16% versus 25%. Overall, ARIA-related events were reported in 29% of patients on the new regimen. No new safety concerns were identified, although hypersensitivity and infusion reactions were more common.
“This update reflects our commitment to patient safety and treatment optimization,” said Dr. Brandy Matthews, Lilly’s VP of Global & US Medical Affairs for Alzheimer’s.
Kisunla received FDA approval in July 2024 after the TRAILBLAZER-ALZ 2 study showed it slowed cognitive and functional decline by up to 35% in early-stage patients.