New Titration Schedule for Kisunla/Donanemab Approved by FDA

The Food and Drug Administration (FDA) has approved a new titration dosing schedule for Kisunla (donanemab-azbt; Eli Lilly and Company, Indianapolis, IN), which is intended to lower the risk of amyloid-related imaging abnormalities with edema/effusion (ARIA-E) in the treatment of people with early symptomatic Alzheimer disease (AD). The updated label—based on findings from the TRAILBLAZER-ALZ 6 trial (NCT05738486)—preserves Kisunla’s therapeutic effect while significantly reducing ARIA-E incidence.

Kisunla is administered once monthly and indicated for adults with mild cognitive impairment or mild dementia due to AD, confirmed by amyloid pathology. The revised regimen gradually escalates the dose by shifting the second vial from the initial dose to the third dose, delivering the same cumulative drug amount by week 24.

In TRAILBLAZER-ALZ 6, 843 participants 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. The primary end point of the study was the percentage of participants with any occurrence of ARIA-E through 24 weeks. Key findings from TRAILBLAZER-ALZ 6 comparing the original dosing regimen to the newly approved, modified titration schedule are as follow:

• At week 24, there was a 41% lower relative risk of ARIA-E associated with the modified titration schedule, occurring in 14% of this treatment arm vs 24% of those receiving the original regimen.
• At week 52, there was a 35% lower relative risk of ARIA-E associated with the modified titration schedule, occurring in 16% of this treatment arm vs 25% of participants receiving the original regimen.
• Amyloid plaque levels measured via PET were reduced by 67% from baseline on average for those receiving the modified titration schedule vs a 69% reduction for those receiving the original regimen.
• Phosphorylated tau217 (p-tau217) level reductions were similar between the 2 treatment arms.
• Of participants receiving the modified titration schedule, 25% showed ARIA with hemorrhage (ARIA-H).
• There were no new adverse events observed: hypersensitivity and infusion-related reactions occurred more often with the modified schedule vs the original regimen.

“This updated dosing strategy is a meaningful advancement for patients and their care teams,” said Elly Lee, MD, Chief Medical Officer and Principal Investigator at the Irvine Center for Clinical Research. “By significantly reducing the risk of ARIA-E, we can offer patients and care teams greater confidence in the safety of Kisunla while preserving its ability to reduce amyloid.”