NEW YORK – Eli Lilly on Tuesday said that it will discuss with global regulators data on a modified dosing regimen for its beta-amyloid-targeting Alzheimer's disease drug Kisunla (donanemab) with plans to submit data for a potential label update.
The US Food and Drug Administration approved Kisunla in July as a treatment to slow Alzheimer's progression for patients with early disease by removing beta-amyloid plaques in the brain. Patients receive intravenous infusions of Kisunla at a lower dose monthly for the first three months, at which point the dose increases. They're able to stop the drug after meeting a threshold of beta-amyloid plaque removal.
At the Clinical Trials on Alzheimer's Disease Conference in Madrid, Lilly shared results of the TRAILBLAZER-ALZ 6 Phase IIIb trial, in which the company is investigating the effect of four dosing regimens of Kisunla on drug efficacy and rates of amyloid-related imaging abnormalities with edema (ARIA-E), an adverse event observed in patients taking this class of drugs.
Lilly found that when investigators shifted one vial of Kisunla from the first infusion to the third infusion, patients experienced a reduction in ARIA-E.
After 24 weeks of being on treatment, ARIA-E was observed in 14 percent of patients who received this modified dosing regimen compared to 24 percent of patients who received standard dosing. This dosing modification led to the largest reduction in ARIA-E compared to the other dosing approaches studied in the clinical trial.
APOE ε4 homozygous patients, who are known to be at high risk for ARIA, experienced the largest ARIA-E reduction. Nineteen percent of these patients who received the modified dosing regimen had ARIA-E compared to 57 percent who received standard dosing, which represents a 67 percent lower relative risk, according to Lilly.
Reductions in beta-amyloid plaque and phosphorylated-tau 217, two biomarkers associated with Alzheimer's, were comparable between the modified and standard dosing regimens.
Aside from ARIA-E rates, the safety profiles between the modified and standard dosing regimens were comparable. However, one patient in the modified dosing arm with ongoing ARIA-E presented with stroke-like symptoms, and after receiving tissue-type plasminogen activator treatment, died due to cerebral intraparenchymal hemorrhage.
"Lilly is committed to continuing research to optimize therapy for patients with Alzheimer's disease," Mark Mintun, Lilly's group VP of neuroscience R&D, said in a statement. "We are confident in the benefits of Kisunla's currently approved dosing regimen and are excited that these results reveal a path to potentially improving on Kisunla's profile by reducing the risk of ARIA-E."
The TRAILBLAZER-ALZ 6 study is ongoing with data on patients 52 weeks after starting treatment expected early next year.