Patient Deaths in Phase 3 Trial of Eli Lilly's Donanemab

The Eli Lilly Company and its associates have recently unveiled promising outcomes from their Trailblazers-ALZ 6 study, a Phase 3b clinical trial. This trial examined the effects of donanemab in individuals with early symptomatic Alzheimer's disease (AD). The study's findings, presented publicly at the 17th Alzheimer's Disease Clinical Trials (CTAD) Conference in Madrid, Spain, demonstrated a significant reduction in amyloid-related imaging abnormalities (ARI-E) among patients treated with a slightly modified titration of donanemab over a 24-week period. Donanemab, marketed under the brand name Kisunla, is currently approved for Alzheimer's treatment in the United States, Japan, and the United Kingdom, along with several other countries.

The ALZ 6 study is a comprehensive, multicenter, randomized, double-blind Phase 3b clinical trial. The primary aim of this study was to evaluate the impact of various doses of donanemab on amyloid clearance and ARI-E in patients with early symptomatic Alzheimer's disease, which includes mild cognitive impairment (MCI) and mild dementia stages of AD. During the study, one participant from the modified titration group experienced persistent ARI-E and stroke-like symptoms. Emergency response included the administration of tissue type plasminogen activator therapy (tPA); however, the participant tragically passed away due to brain hemorrhage. The US Food and Drug Administration (FDA) cautions that extreme care should be taken when using thrombolytic agents like tPA in patients who have received amyloid-targeted treatments.

Eli Lilly is currently engaging with global regulators to discuss the study findings and is considering submitting Kisunla for a potential label update. TRAILBLAZER-ALZ 6 (NCT05738486) is a Phase 3b, multicenter, randomized, double-blind study that explores different dosing regimens and their effects on ARI-E in adults with early symptomatic disease. The trial included 843 participants aged between 60 and 85, who were chosen based on cognitive assessments and amyloid plaque imaging from PET scans.

Eli Lilly is continuing its research on donanemab through several clinical trials. Among these are the Trailblazers-ALZ 3 study, which focuses on reducing the risk of progression to symptomatic AD in preclinical AD participants, and the Trailblazers-ALZ 5 study, a registered trial for early symptomatic Alzheimer's disease that is currently being conducted in China, South Korea, Taiwan, and other locations.

Kisunla, or donanemab-azbt, is an amyloid-targeted therapy designed for patients with the mild dementia stage of early symptomatic Alzheimer's disease and confirmed amyloid pathology. It is essential to remember that the side effects mentioned above are not exhaustive of all possible side effects associated with Kisunla.