The U.S. Food and Drug Administration (FDA) has approved a label update with a new recommended titration dosing schedule for Eli Lilly and Co.’s LLY Kisunla (donanemab-azbt) once-monthly amyloid-targeting therapy for adults with early symptomatic Alzheimer’s disease (AD). The FDA approved the drug in July 2024.
In the TRAILBLAZER-ALZ 6 study, the modified titration schedule significantly reduced the incidence of amyloid-related imaging abnormalities with edema/effusion (ARIA-E) compared to the original dosing schedule at 24 and 52 weeks, while still achieving similar levels of amyloid plaque removal and P-tau217 reduction.
The new recommended dosing regimen involves a more gradual titration.
ARIA-E is a side effect of amyloid plaque-targeting therapies, including Kisunla. ARIA-E is usually asymptomatic, although serious and fatal events can occur.
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The new dosing recommendation differs from the original dosing by shifting a single vial from the first dose to the third dose, delivering the same amount of Kisunla by week 24.
This resulted in lower rates of ARIA-E without compromising Kisunla’s ability to reduce amyloid plaque or its once-monthly dosing, with the potential for a limited-duration treatment based on amyloid plaque removal to minimal levels.
Key findings from the TRAILBLAZER-ALZ 6 study, which supports this label update, included:
- The results showed that the incidence of ARIA-E was 14% in patients receiving the modified titration regimen compared with 24% for those receiving the original dosing regimen, representing a 41% lower relative risk.
- At week 52, the incidence of ARIA-E was 16% in patients receiving the modified titration compared with 25% for those receiving the original dosing regimen, a 35% lower relative risk.
- Including asymptomatic radiographic events at week 52, ARIA, ARIA-E, and ARIA-H were observed in 29%, 16%, and 25% of patients receiving the modified titration dosing.
- ARIA-E and ARIA-H are different types of amyloid-related imaging abnormalities (ARIA). ARIA with edema is characterized as ARIA-E, and ARIA with hemosiderin deposition is characterized as ARIA-H.
Patients on the modified titration experienced a reduction of amyloid plaque and P-tau217 comparable to patients receiving the original dosing regimen.
At 24 weeks, amyloid plaque levels in patients on the modified titration of donanemab in TRAILBLAZER-ALZ 6 were reduced on average by 67% from baseline compared to 69% for patients on the original dosing regimen.
No new adverse reactions were identified in the study, although higher rates of hypersensitivity and infusion-related reactions were observed.
In March, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) issued an opinion that does not recommend Eli Lilly’s donanemab be granted marketing authorization in early symptomatic Alzheimer’s disease. Lilly will seek re-examination by CHMP.
Price Action: LLY stock is up 0.30% at $780 during the premarket session at the last check on Wednesday.
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