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 Helps Explain Clinical Response

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.

Disease Course Stabilized 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

Tramiprosate Stops Brain Atrophy in AD Patients

Hippocampus Volume Loss Very Prominent in APOE4/4 AD Patients

block-hippocampus-brain-atrophy

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

Summary of Clinical Data in Alzheimer’s Patients

APOE4/4 with Early Alzheimer’s = Initial Population for ALZ-801

  • Clinical benefits in APOE4/4 patients with mild Alzheimer’s disease
    • Significant benefit on cognition & daily function
    • Disease-stabilizing effect on function
    • Persistence of benefit over 2.5 years
    • Effects are clinically meaningful (~100% vs. 25% threshold)
  • Well tolerated, long-term safety at effective clinical dose
    • Drug exposures in >1,600 patients up to 1.5 years
    • Long term safety in ~400 patients up to 2.5 years
    • Most common adverse events: nausea, vomiting
    • No brain swelling (ARIA-E) on active drug in 426 patients
  • Endogenous metabolite of tramiprosate helps explain favorable safety & potential efficacy of ALZ-801
  • Differentiated program with promising efficacy in patients with Alzheimer’s dementia
Alzheon publications: Abushakra (2016) J Prev Alz Dis; Abushakra (2017) J Prev Alz Dis; Hey (2018) CNS Drugs

ALZ-801 vs. BAN2401 Antibody*

Targeting of Amyloid Oligomers Leads to Clinical Benefits in AD

BAN2401 Antibody  ALZ-801
Binds large oligomers >> monomers > insoluble plaques Inhibits formation of soluble oligomers,
no plaque binding
Brain penetration ~0.3% ~40% of oral dose
More robust effects in APOE4 carriers
Target population Early AD
APOE4/4 homozygotes
Early to mild AD
 Clinical benefits on ADAS-cog ~80% & CDR-SB ~60% ADAS-cog ~120% & CDR-SB ~80%
Brain swelling (ARIA-E) ~10-15% No brain swelling
Bi-weekly IV infusion Oral pill
*Not a head-to-head comparison
Source:  Profile of BAN2401 is based on peer reviewed publications and information disclosed by competitors