Alzheon has received a $47m five-year grant from the US National Institute on Aging (NIA) to conduct a Phase III clinical trial of ALZ-801 as an oral treatment for Alzheimer’s disease.
ALZ-801 is designed to inhibit the formation of neurotoxic soluble amyloid oligomers. It is a brain-penetrant, small molecule prodrug of the active agent tramiprosate.
The Phase III trial will involve early Alzheimer’s patients with two copies of the apolipoprotein e4 allele (APOE4/4).
This patient population is known to be at a higher risk of rapid disease progression and could be responsive to agents targeting pathogenic amyloid oligomers.
Alzheon said that the trial will assess the drug candidate in 300 patients, who will be given 265mg tablets of ALZ-801 or a matching placebo twice daily over 18 months.
The primary clinical outcome is cognitive endpoint on Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog). The trial will also track functional, behavioural, and global clinical endpoints.
Biomarker assessments will include plasma and cerebrospinal fluid (CSF) measures of core disease pathologies and neurodegeneration, and neuroinflammatory markers.
Imaging biomarkers will assess measurements of hippocampal volume and cortical thickness. The study is expected to launch in the first quarter of next year.
Alzheon chief medical officer Susan Abushakra said: “We are applying precision medicine by targeting patients who can be readily diagnosed, who develop the disease earlier when they are less likely to have comorbidities, and who are likely to benefit from the treatment.
“We are integrating advanced fluid biomarkers into Phase III programme to increase our understanding of the effects of ALZ-801 treatment on the course of the disease.”
The company plans to expand the evaluation of ALZ-801 in prevention trials in healthy participants with high Alzheimer’s risk, and in APOE4 heterozygotes with one copy of the APOE4 gene.