Lilly reduces brain swelling by changing the dosage of the Alzheimer's drug Kisunla

Eli Lilly on Tuesday presented data from the phase IIIb study TRAILBLAZER-ALZ 6showing that a “slightly modified” dosage regimen of its Alzheimer's therapy Kisunla resulted in a reduction in the frequency of brain swelling.

Currently, Kisunla's approved dosing schedule calls for an intravenous infusion of 700 mg for the first three doses, followed by doses of 1,400 mg every four weeks. The regimen has been linked to several safety concerns, which the FDA declared in June 2024 labeled as “death imbalance.” in patients treated with the antibody. Kisunla's label carries a boxed warning in amyloid-related imaging abnormalities (ARIA) with edema or hemosiderin deposits, although this is typical of anti-amyloid therapies.

In TRAILBLAZER-ALZ 6, Lilly lowered the first Kisunla dose to 350 mg before increasing it to 700 mg for the second infusion and to 1,050 mg for the third dose. Patients then received the usual dose of 1,400 mg according to the Kisunla-approved dosing schedule.

Results showed that ARIA with edema (ARIA-E) occurred in 14% of patients in the modified dose arm compared to 24% of patients in the standard regimen. According to Lilly, the difference in incidence corresponded to a 41% lower relative risk of ARIA-E.

The safety benefits of the adjusted dosage were greater in patients with a known genetic risk factor for Alzheimer's disease or those known to be apolipoprotein E homozygotes. These patients saw a 67% lower relative risk of ARIA-E with the changed schedule.

Reducing the starting dose of Kisunla did not appear to affect its effectiveness. Patients on the adjusted treatment regimen achieved similar reductions in amyloid plaque and P-Tau217 levels as comparator patients on the standard dose regimen. Lilly did not report cognitive outcomes in patients, but said in its announcement that “removing amyloid plaques from the brain may result in a statistically significant slowing of cognitive and functional decline in patients.”

One patient treated with the adjusted dosage regimen died. The patient had persistent ARIA-E and presented with “stroke-like symptoms” and was treated with tissue-type plasminogen activator treatment.

Mark Mintun, group vice president of neuroscience research and development at Lilly, said in a statement that Kisunla's modified titration regimen “could continue to provide the convenience of once-monthly dosing and limited treatment duration, while reducing ARIA-E and similar amyloid plaque.” distance could be maintained.”

According to the company, Lilly will use the results for TRAILBLAZER-ALZ 6 as the basis for a regulatory update application for Kisunla.