Alzheon, a clinical-stage biopharmaceutical company developing therapies and diagnostics for Alzheimer’s disease (AD) and other neurodegenerative disorders, has recently announced the publication of its APOLLOE4 Phase III clinical trial results in the journal Drugs. APOLLOE4 was a 78-week, randomised, double-blind, placebo-controlled, parallel-arm and multicenter study in people with early AD, who carry two copies of the apolipoprotein E ε4 allele (APOE4/4 homozygotes). The trial enrolled 325 participants across North America and Europe. Participants received either placebo or valiltramiprosate (ALZ-801), an oral small-molecule investigational therapy, at 265 mg twice daily. There was a specific effort in the United States to increase representation of underrepresented populations to maximise the diversity, equity, and inclusiveness of the study.
The APOE4/4 early AD population did not show significant clinical efficacy at 78 weeks but showed significant brain atrophy slowing. Prespecified analyses at the Mild Cognitive Impairment (MCI) stage showed nominally significant slowing of clinical decline with significant hippocampal atrophy slowing. Additionally, valiltramiprosate treatment was associated with a favorable safety profile, showing no increased risk of amyloid-related imaging abnormalities (ARIA). Data on the APOLLOE4 Phase III clinical trial will be presented at the upcoming Clinical Trials on Alzheimer’s Disease (CTAD) conference in San Diego, California, as well as new efficacy and safety data from the Phase II study long term extension over 3 years. The paper can be accessed at: https://doi.org/10.1007/s40265-025-02250-5