Approved by the FDA in July to treat adults with early symptomatic Alzheimer’s disease, Eli Lilly’s Kisunla reduced the brain swelling of patients in a late-stage trial following an adjusted dosing regimen.
Eli Lilly on Tuesday unveiled data from the Phase IIIb TRAILBLAZER-ALZ 6 study, demonstrating that a “slightly modified” dosing regimen of its Alzheimer’s disease therapy Kisunla led to a reduction in the incidence of brain swelling.
Currently, Kisunla’s approved dosing schedule involves a 700-mg intravenous infusion for the first three doses, followed by 1,400-mg doses every four weeks. The regimen has been associated with several safety concerns, which the FDA in June 2024 flagged as an “imbalance of deaths” in patients treated with the antibody. Kisunla’s label carries a boxed warning for amyloid-related imaging abnormalities (ARIA) with edema or with hemosiderin deposition, though this is typical of anti-amyloid therapies.
In TRAILBLAZER-ALZ 6, Lilly lowered the first dose of Kisunla to 350 mg before ramping it up to 700 mg for the second infusion and 1,050 mg for the third dose. Thereafter, patients were given the usual 1,400-mg dose, in accordance with Kisunla’s approved dosing schedule.
Results showed that ARIA with edema (ARIA-E) developed in 14% of patients in the modified dosing arm, compared to 24% of those on the standard schedule. The difference in incidence corresponded to a 41% lower relative risk of ARIA-E, according to Lilly.
The safety benefits of the adjusted dosing were greater in patients with a known genetic risk factor for Alzheimer’s disease, or those who were known as apolipoprotein E homozygotes. These patients saw a 67% lower relative risk of ARIA-E with the modified schedule.
Lowering the initiation doses of Kisunla did not seem to compromise its efficacy. Patients on the adjusted schedule achieved similar levels of reduction in amyloid plaque and P-tau217 levels as comparators on the standard dosing. Lilly did not report cognitive outcomes for patients, but said in its announcement that “the removal of amyloid plaque from the brain can lead to statistically significant slowing of cognitive and functional decline in patients.”
One patient treated with the adjusted dosing schedule died. The patient had ongoing ARIA-E and presented with “stroke-like symptoms,” and was managed with tissue-type plasminogen activator treatment.
Mark Mintun, group vice president of neuroscience R&D at Lilly, in a statement said that Kisunla’s modified titration regimen “could offer continued convenience of once-monthly dosing and limited duration treatment while also reducing ARIA-E and maintaining similar amyloid plaque removal.”
Lilly will use the findings for TRAILBLAZER-ALZ 6 as the basis for a label update filing for Kisunla, according to the company.
