Underlying Clinical Data 2018-02-07T10:57:12+00:00

Clinical Data

From 2004 to 2008, tramiprosate was evaluated in more than 2,000 patients with AD 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 AD over a 78-week treatment period. Efficacy was evaluated using ADAS-cog and CDR-SB.

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.

Favorable long-term safety was observed in these trials with the most commonly observed adverse events being 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 – the Most Homogeneous AD 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.

APOE4/4 Homozygotes Most Responsive Subgroup

Based on Large Clinical Dataset with Tramiprosate

Alzheon-APOE4 heterozygotes

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

More Pronounced Benefits in APOE4/4 at Mild AD

Tramiprosate North American Trial: MMSE 22-26*

Alzheon_ALZ-801-medicine for alzheimers_15V2

About ALZ-801

Summary of Clinical Data

APOE4/4 Mild Alzheimer’s Patients are the Initial Target Population for ALZ-801.

  • Meaningful & sustained clinical benefit in APOE4/4 mild AD patients – most amyloid-driven AD 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)
  • Favorable long-term safety & acceptable tolerability at effective clinical dose observed
    • Unique drug exposures in >1,600 patients up to 1.5 years
    • Drug exposures in ~400 patients up to 2.5 years
    • Most common AE’s nausea, fall, dizziness, weight loss and urinary track infection
    • No vasogenic brain edema (ARIA-E) on active drug in 426 patients
  • Differentiated program with promising efficacy & favorable safety profile
*Alzheon publications:  Abushakra (2016) J Prev Alz Dis; Abushakra (2017) J Prev Alz Dis