US pharmaceutical major Eli Lilly and Company (NYSE: LLY) has revealed the complete results of the Phase III TRAILBLAZER-ALZ 2 study for donanemab, demonstrating that the drug significantly slowed cognitive and functional decline in patients with early symptomatic Alzheimer’s disease (AD).
Donanemab’s Efficacy in Early Symptomatic Alzheimer’s Disease
The study showed that donanemab significantly slowed cognitive and functional decline for amyloid-positive early symptomatic Alzheimer’s disease patients, reducing their risk of disease progression. Nearly half of the participants at an earlier stage of the disease on donanemab had no clinical progression at one year. Subpopulation analyses revealed that participants at the earliest stage of the disease experienced even greater benefits, with a 60% slowing of decline compared to placebo. The treatment effect continued to increase relative to placebo over the course of the trial, supporting the potential for limited duration dosing. The FDA submission was completed in Q2, with regulatory action expected by the end of the year.
Design and Outcomes of the TRAILBLAZER-ALZ 2 Study
The double-blind, placebo-controlled Phase III study aimed to evaluate the safety and efficacy of donanemab in participants aged 60-85 years with early symptomatic Alzheimer’s disease (mild cognitive impairment or mild dementia due to Alzheimer’s disease) and confirmed Alzheimer’s disease neuropathology. The study enrolled 1736 participants across eight countries, selected based on cognitive assessments in conjunction with amyloid plaque imaging and tau staging by PET imaging. Treatment with donanemab reduced amyloid plaque on average by 84% at 18 months, compared with a 1% decrease for participants on placebo. Participants were able to discontinue donanemab once they achieved pre-defined criteria of amyloid plaque clearance.
Ongoing Clinical Trials for Donanemab
Eli Lilly continues to investigate donanemab in multiple clinical trials. These include the TRAILBLAZER-ALZ 3, which focuses on preventing symptomatic Alzheimer’s disease in participants with preclinical AD; the TRAILBLAZER-ALZ 5, a registration trial for early symptomatic Alzheimer’s disease currently enrolling in China; and the TRAILBLAZER-ALZ 6, which aims to expand understanding of ARIA through novel MRI sequences, blood-based biomarkers, and different dosing regimens of donanemab.-Fineline Info & Tech
