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.

Focus on APOE4/4 patients with highest levels of toxic oligomers

APOE4/4 patients = high risk & rapid disease progression

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.

Meaningful effects on ADAS-cog & CDR-SB

Tramiprosate on top of standard of care: MMSE 16-26^

Alzheon-APOE4 heterozygotes

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

Mild AD patients stay above baseline for 18 months

Subgroup: APOE4/4 Homozygotes with Mild AD, MMSE 22-26^

Alzheon_ALZ-801-medicine for alzheimers_15V2

Hippocampus atrophy prominent in APOE4/4 AD

Tramiprosate protects from hippocampus atrophy in AD patients

block-hippocampus-brain-atrophy

*Images courtesy of Dr. Jeff Cummings – Cleveland Clinic
**Gauthier (2009) Nutr Health Aging
About ALZ-801

Key findings of Tramiprosate Phase 3 program

Established effective dose & optimal initial APOE4/4 target population

  • Significant efficacy in cognition & daily function in pre-defined APOE4 subgroups
    • Clinical benefit increases with APOE4 gene dose
    • Disease course stabilized in APOE4 homozygotes with Mild AD
    • No loss of hippocampal volume over 18 months
    • Persistence of clinical benefits over 2.5 years
    • ~30% of patients enrolled in tramiprosate Phase 3 trials did not have AD
      • AD could not accurately be diagnosed at the time these trials were designed & carried out
  • Favorable safety
    • Well tolerated, with no evidence of brain swelling or microbleeds (ARIA)
      • No brain swelling (ARIA-E) in MRI subgroup of 426 patients
    • Most common adverse events:  Nausea & vomiting
    • Safety database sufficient for NDA: 1,600 patients up to 1.5 years & 400 up to 2.5 years
Alzheon publications: Abushakra (2016) J Prev Alz Dis; Abushakra (2017) J Prev Alz Dis; Hey (2018) CNS Drugs