Development of ALZ-801 2016-12-05T13:05:26+00:00


First alzheon pill

An orally administered drug candidate with the ability to interfere with the beta amyloid pathology of Alzheimer’s disease.

ALZ-801 is an orally administered, optimized prodrug of the active molecule tramiprosate. Our team had the insight to reexamine the tramiprosate data from two large Phase 3 studies in more than 2,000 patients with Alzheimer’s disease (AD). Then, using a precision medicine approach, we created a prodrug, ALZ-801, to improve the critical pharmaceutical properties of tramiprosate – tolerability, pharmacokinetic and pharmacodynamic profile, and metabolic stability – to make our drug candidate better suited as a treatment for patients with AD.  

Accelerating ALZ-801

Applying our understanding of the genetics of AD, has enabled the acceleration of prodrug ALZ-801 into late-stage clinical development. Since the initial clinical evaluation of the active molecule tramiprosate, the role of genetics in influencing the response to AD treatments has become an important consideration. The ε4 allele of apolipoprotein E (APOE4) is the strongest genetic risk factor for patients with late-onset AD, and is associated with greater beta amyloid pathology in the brain. APOE4 is currently the most important biomarker to identify and stratify Alzheimer’s patients.

Our development plan for ALZ-801 is focusing on the APOE4 gene to identify patients who have the greatest urgency and medical need, and in whom the drug candidate is expected to have the most robust clinical effect.

ALZ-801 US Population with APOE4:4

APOE4 is the strongest genetic risk factor for patients with late-onset Alzheimer’s disease.

We applied this genetic understanding of APOE4 in AD to re-analyze the clinical data from prior Phase 3 studies with the active molecule tramiprosate, which demonstrated safety but did not show conclusive clinical efficacy. Our team completed an extensive subgroup analysis of APOE4-positive patients receiving the active molecule tramiprosate and found a clinically compelling and statistically significant improvement in cognition (as measured on the ADAS-cog scale, nominal p-values < 0.05), as well as a positive trend on function (as measured on the CDR-SB scale) that was sustained through 18 months of treatment (Abushakra et al., 2016).  Importantly, the efficacy was demonstrated on top of the maximum standard of care symptomatic therapy currently used today. The Phase 3 studies of tramiprosate demonstrated a favorable safety profile, which can be leveraged in the pivotal clinical program for ALZ-801.

Our development program is designed to confirm the efficacy of ALZ-801 in the treatment of AD. Based on the compelling efficacy in subgroup analyses of APOE4 gene carriers, our first studies will be in patients who are homozygous for APOE4 (APOE4/4). These patients suffer from the most aggressive disease course but, as our data suggest, can derive the strongest potential benefit from a beta amyloid-targeted therapy.  Moreover, APOE4 is a reliable biomarker for AD patient identification, allowing us to greatly improve diagnostic accuracy, a problem which has plagued previous Alzheimer’s studies.

Because beta amyloid aggregation is the key underlying mechanism that is commonly recognized to drive the Alzheimer’s disease pathology, and our drug effectively blocks this process, all patients with Alzheimer’s disease may benefit from ALZ-801. We have designed a sequential development program for ALZ-801, starting with studies in genetically-defined Alzheimer’s patient populations, followed by an expansion into a broader population of all patients with AD.  Learn about the Underlying Clinical Data of ALZ-801 here.