Eli Lilly and Company (Lilly) revealed complete results from its Phase 3 TRAILBLAZER-ALZ 2 study at the 2023 Alzheimer’s Association International Conference (AAIC), indicating that the experimental drug, donanemab, significantly slowed the cognitive and functional decline in patients with early symptomatic Alzheimer’s disease.

The data was simultaneously published in the Journal of the American Medical Association (JAMA).

Anne White, Executive Vice President of Eli Lilly and President of Lilly Neuroscience, commented on the breakthrough: “The positive TRAILBLAZER-ALZ 2 data bring hope to people with Alzheimer’s disease who urgently need new treatment options. This is the first Phase 3 study of a disease-modifying therapy to replicate the positive clinical results observed in a previous study.”

The American pharma giant had earlier announced that donanemab met primary and all cognitive and functional secondary endpoints in the Phase 3 study. The submission for approval was completed last quarter with the US Food and Drug Administration (FDA), with regulatory action anticipated by year-end. Submissions to other global regulators are ongoing, and the majority are expected to be completed by the year-end.

The TRAILBLAZER-ALZ 2 study involved participants with a broader range of cognitive scores and amyloid levels compared to other recent trials of amyloid plaque-targeting therapies. All participants were assessed over 18 months using the integrated Alzheimer’s Disease Rating Scale (iADRS) and the Clinical Dementia Rating-Sum of Boxes (CDR-SB).

As previously reported, donanemab treatment significantly slowed decline among participants with low-medium levels of tau, a predictive biomarker for disease progression. The overall treatment effect of donanemab continued to grow throughout the trial, with the largest differences versus placebo seen at 18 months.

Donanemab, which specifically targets deposited amyloid plaque, has been shown to lead to plaque clearance in treated patients. Among all participants, treatment with donanemab reduced amyloid plaque on average by 84% at 18 months, compared with a 1% decrease for participants on placebo.

The TRAILBLAZER-ALZ 2 is a double-blind, placebo-controlled study to evaluate the safety and efficacy of donanemab in participants aged 60-85 years with early symptomatic Alzheimer’s disease. The trial enrolled 1,736 participants, across eight countries, selected based on cognitive assessments in conjunction with amyloid plaque imaging and tau staging by PET imaging.

  Alzheimer’s Disease, Anne White, Eli Lilly and Company, Lilly, USA