Underlying Clinical Data2018-10-01T13:58:13+00:00

Clinical Data

From 2004 to 2008, 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 the trials were to evaluate the efficacy and safety of tramiprosate in patients with mild to moderate Alzheimer’s over a 78-week treatment period. Efficacy was evaluated using ADAS-cog (cognitive scale) and CDR-SB (functional scale).

The primary efficacy analysis of all subjects (i.e., the Intent-to-Treat population, ITT) in the North American Phase 3 study did not show a statistically significant difference between the treatment and placebo groups for the primary efficacy endpoints (ADAS-cog and CDR-SB). The European, Phase 3 trial with tramiprosate was terminated early after the results of the North American study became known.

Most commonly observed adverse events in these trials were nausea, vomiting and weight loss. Blood levels of tramiprosate in these patients showed substantial variability.

In 2013, we licensed ALZ-801 and preclinical and clinical data for tramiprosate from FB Health S.p.A., or FB Health, which holds a license from BHI Limited Partnership, an affiliate of Bellus, following Bellus’ decision to discontinue its Phase 3 program of tramiprosate.

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.

APOE4 Genotype Explains Clinical Response

Targeting APOE4/4 Patients – High Risk & Homogeneous Alzheimer’s Population

Alzheon APOE4 heterozygotes

We systematically analyzed the data set based on the number of APOE4 alleles. Approximately 60%, or 627, of the patients enrolled in the trial were APOE4 carriers, of whom 475 patients were APOE4 heterozygotes and 152 patients were APOE4/4 homozygotes.

Benefits in APOE4/4 with Mild to Moderate Alzheimer’s

Tramiprosate on Top of Standard of Care in North American Trial: MMSE 16-26^

Alzheon-APOE4 heterozygotes

We subsequently analyzed these data based on disease stage at the onset of the trial.

Compelling Effects in APOE4/4 with Mild Alzheimer’s

Tramiprosate on Top of Standard of Care in North American Trial: MMSE 22-26^

Alzheon_ALZ-801-medicine for alzheimers_15V2

About ALZ-801

Summary of Clinical Data in Alzheimer’s Patients

APOE4/4 Early to Mild Alzheimer’s Patients = Initial Target Population for ALZ-801

  • Meaningful & sustained clinical benefits in genetically-defined APOE4/4 patients with mild Alzheimer’s disease = most amyloid oligomer driven population
    • Significant benefit on cognition
    • Disease-stabilizing effect on function
    • Persistence of efficacy over 2.5 years
    • Magnitude of effects clinically meaningful (~100% vs. 25% threshold)
  • Well tolerated, long-term safety evaluated at effective clinical dose
    • Unique drug exposures in >1,600 patients up to 1.5 years and in ~400 patients up to 2.5 years
    • Most common adverse events included nausea, falls, dizziness, weight loss & urinary tract infections
    • No brain swelling (ARIA-E) on active drug in 426 patients
    • Endogenous nature of major metabolite of tramiprosate may help explain safety, excellent brain penetration & potential efficacy of ALZ-801
  • Differentiated program with promising efficacy in Alzheimer’s patients
Alzheon publications: Abushakra (2016) J Prev Alz Dis; Abushakra (2017) J Prev Alz Dis; Hey (2018) CNS Drugs