Aims

Background

ALZ-801 (valiltramiprosate) is an oral, brain-penetrant, small molecule inhibitor of amyloid oligomer formation in development for Alzheimer’s disease (AD). ALZ-801 is being evaluated as a disease-modifying treatment in two ongoing Early AD trials: fully enrolled Phase 2 study in APOE4 carriers and APOLLOE4 Phase 3 study in APOE4/4 homozygotes.

Objectives

Evaluate results from pre-specified interim analysis at 52 weeks on plasma biomarkers of AD, hippocampal volume (HV), and clinical outcomes.

Methods

Methods

Open-label Phase 2 biomarker study evaluating ALZ-801 265 mg BID in Early AD subjects (MMSE 22-30) with APOE4/4 or APOE3/4 genotype is conducted at 7 sites in the Czech Republic and Netherlands. Biomarker analyses completed at the Clinical Neurochemistry Laboratory of Gothenburg University, Sweden, were blinded to demographics or genotype. The primary biomarker outcome was p-tau₁₈₁ and HV was the primary imaging outcome. The HV atrophy was compared to matched external control subjects from AD Neuroimaging Initiative cohort (ADNI).

Results

Results

A total of 84 APOE4 carriers enrolled and received ALZ-801, and 80 and 75 subjects completed 26 and 52 weeks, respectively. Plasma p-tau₁₈₁ change from baseline was significant at 13 and 26 weeks and reached -41% at 52 weeks (p=0.016). Bilateral HV atrophy at 1 year was reduced by 25% compared to the matched ADNI subjects. Most common adverse events were mild nausea and COVID infection, with no drug-related serious events and no events of ARIA-E in 75 subjects at 52 weeks.

Conclusions

The significant effects on plasma biomarkers, HV and clinical benefits support the disease modifying potential of ALZ-801 in AD. The favorable safety, low risk of ARIA-E, and convenience of a simple oral regimen, make ALZ-801 an attractive potential treatment with wide access for AD patients.