Eli Lilly's Donanemab Leads to Patient Deaths in Key Phase 3 Trial

The Eli Lilly Company and its partners recently announced positive results from the Trailblazers -ALZ 6 study, a Phase 3b clinical trial evaluating donanemab in patients with early symptomatic Alzheimer's disease (AD). The results of the study showed that the primary endpoint at 24 weeks showed a significant reduction in amyloid-related edema/effusion imaging abnormalities (ARI-E) in patients who received a slightly modified titration with donanemab. Donanemab as a treatment for Alzheimer's disease is already approved under the brand name Kisunla in the United States, Japan, and the United Kingdom, as well as in a number of other countries. These encouraging data were presented to the public at the 17th Alzheimer's Disease Clinical Trials (CTAD) Conference in Madrid, Spain.

The ALZ 6 study is a multicenter, randomized, double-blind Phase 3b clinical trial whose primary objective was to investigate the effects of different doses of donanemab in patients with early symptomatic Alzheimer's disease, including mild cognitive impairment (MCI) and adult AD in mild dementia stages, specifically on amyloid clearance and ARI-E. In this study, one participant in the modified titration group developed persistent ARI-E and stroke-like symptoms. In an emergency, the patient was treated with tissue type plasminogen activator therapy (tPA) but unfortunately subsequently died due to hemorrhage within the brain parenchyma. As the US Food and Drug Administration (FDA) notes in its drug label, extreme caution should be exercised when considering agents such as thrombolytic agents (such as tPA) in patients who have already received amyloid-targeted therapy.

Eli Lilly is currently discussing the study's findings with regulators around the globe and plans to submit Kisunla for a potential label update. TRAILBLAZER-ALZ 6 (NCT05738486) is a phase 3b, multicenter, randomized, double-blind study investigating different dosing regimens and their effects on ARI-E in adults with early symptomatic disease. The trial enrolled a total of 843 participants between the ages of 60 and 85 who were selected based on cognitive assessment and amyloid plaque imaging from PET scans.

Eli Lilly continues to study donanemab in multiple clinical trials, including Trailblazers -ALZ 3, which is focused on reducing the risk of progression to symptomatic AD in preclinical AD participants; And Trailblazers -ALAZ 5, a registered trial for early symptomatic Alzheimer's disease currently registered in China, South Korea, Taiwan, and elsewhere. About Kisunla (donanemab-azbt) (pronounced kih-SUHN-lah), an amyloid-targeted therapy for patients with the mild dementia stage of early symptomatic Alzheimer's disease in patients with confirmed amyloid pathology. It's important to note that these aren't all of Kisunla's possible side effects.