Development history of valiltramiprosate/ALZ-801

In 2013, Alzheon licensed valiltramiprosate, preclinical and clinical data for valiltramiprosate predecessor molecule tramiprosate from Bellus Health. Tramiprosate was evaluated in more than 2,000 patients with Alzheimer’s in two Phase 3 clinical trials by Bellus Health Inc.: a North American trial and a European trial. The objectives of these trials were to evaluate the efficacy and safety of tramiprosate in patients with Mild to Moderate Alzheimer’s disease over a 78-week treatment period. Most commonly observed adverse events in these trials were nausea, vomiting and weight loss.

Blood levels of tramiprosate in these patients showed high variability and the analysis of all subjects in the North American study did not show a statistically significant difference between the treatment and placebo groups for the primary efficacy endpoints. Subsequently, the European trial was terminated early after the results of the North American study became known.

Alzheon completed post hoc analyses of Bellus’ Phase 3 North American trial results based on APOE4 status, a pre-defined variable in Bellus’ statistical plan. A systematic analysis of the dataset revealed a promising efficacy signal in a subgroup of patients who were APOE4 carriers. This signal was strongest in mild AD patients who carried 2 copies of the APOE4 allele (APOE4/4). These findings guided development of valiltramiprosate, a valine prodrug of tramiprosate, which is initially focused on APOE4 carriers.

Valiltramiprosate showed improved gastrointestinal tolerability and reliable absorption into the bloodstream in Phase 1 and Phase 2 clinical trials. In completed 2-year Phase 2 biomarker trial, valiltramiprosate treatment lowered plasma p-tau₁₈₁, reduced the rate of hippocampal atrophy, and stabilized clinical AD progression in APOE4 carriers with Early AD and high levels of amyloid and tau pathology.