Lilly Reduces Brain Swelling With Adjusted Dosing of Alzheimer’s Drug Kisunla

Eli Lilly's new Alzheimer's treatment, Kisunla, which received FDA approval in July for early symptomatic Alzheimer's disease in adults, has shown promising results in reducing brain swelling, or amyloid-related imaging abnormalities with edema (ARIA-E), in a late-stage trial with an adjusted dosing regimen.

In a Phase IIIb study, dubbed TRAILBLAZER-ALZ 6, Lilly presented data that demonstrated a modified dosing schedule could lead to a significant reduction in the incidence of ARIA-E. Under the currently approved regimen, patients receive a 700-mg intravenous infusion for the initial three doses, followed by 1,400-mg doses every four weeks. This regimen has raised safety concerns, notably an imbalance in deaths reported by the FDA in June 2024. Kisunla’s label includes a boxed warning for ARIA with edema or hemosiderin deposition, a common issue with anti-amyloid therapies.

In the modified dosing approach tested in TRAILBLAZER-ALZ 6, the first Kisunla dose was reduced to 350 mg, increasing to 700 mg for the second infusion and 1,050 mg for the third dose. Subsequent doses followed the standard 1,400-mg schedule. Results indicated that 14% of patients on the adjusted dosing regimen developed ARIA-E, compared to 24% of those on the standard regimen, translating to a 41% lower relative risk of ARIA-E.

The adjusted dosing regimen proved particularly beneficial for patients with a genetic predisposition to Alzheimer’s disease, specifically apolipoprotein E homozygotes. These individuals experienced a 67% lower relative risk of ARIA-E with the modified regimen.

Importantly, the efficacy of Kisunla was not compromised by the lower initial doses. Patients on the adjusted schedule showed similar reductions in amyloid plaque and P-tau217 levels compared to those on the standard dosing regimen. Although cognitive outcomes were not reported, Lilly noted that amyloid plaque removal is associated with statistically significant slowing of cognitive and functional decline in patients.

Despite these promising results, one patient on the adjusted dosing schedule died. This patient had ongoing ARIA-E and presented with stroke-like symptoms, which were managed with tissue-type plasminogen activator treatment.

Mark Mintun, Lilly’s group vice president of neuroscience research and development, stated that the modified titration regimen of Kisunla "could offer continued convenience of once-monthly dosing and limited duration treatment while also reducing ARIA-E and maintaining similar amyloid plaque removal."

Lilly plans to use the findings from TRAILBLAZER-ALZ 6 to support a label update filing for Kisunla.