On 13 September, Alzheon, Inc., a clinical-stage biopharmaceutical company focused on developing new medicines for neurodegenerative disorders such as Alzheimer’s disease (AD), reported two-year findings from its Phase II trial evaluating ALZ-801 in people with early AD. ALZ-801 is an oral small molecule that works to inhibit the formation of amyloid-beta oligomers or toxic clumps. The open-label, multicenter and single-arm Phase II biomarker trial evaluated biomarker effects, clinical efficacy and safety of ALZ-801 tablet in 84 participants with early AD, who carry either one or two copies of apolipoprotein ε4 allele (APOE4) and showed positivity for amyloid and tau biomarkers in cerebrospinal fluid (CSF). Participants received ALZ-801 (265 mg) tablet once daily for two weeks and twice daily thereafter over a 104-week treatment period. A total of 75 participants completed one year of treatment and 70 of them continued treatment for another year.
68 participants provided evaluable plasma for biomarker assays and were included in the primary analysis. In this population, ALZ-801 achieved a statistically significant reduction in plasma p-tau181, a key biomarker of neurodegeneration, reaching 45% at one year and 31% at two years. Moreover, participants receiving ALZ-801 demonstrated a statistically significant 28% reduction in hippocampus volume at two years, when compared with an external group of early AD patients from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a longitudinal observational multicenter study. On the cognitive scale, as assessed with the Rey Auditory Verbal Learning Test (RAVLT) and the Digit Symbol Substitution Test, participants treated with ALZ-801 demonstrated a consistent improvement after 6 months of treatment and remained stable and above levels at study’s start through two years. Finally, the safety profile of ALZ-801 remains favorable and consistent with the prior safety database of over 2,800 people with AD, with no increased risk of vasogenic brain edema (Amyloid-Related Imaging Abnormalities, or ARIA). Common adverse events experienced in more than 10% of participants were COVID infection, mild nausea and decreased appetite. ALZ-801 is in Phase 3 development for the treatment of early AD. The APOLLOE4 study fully enrolled 325 participants and topline data is expected in the third quarter of 2024.