FRAMINGHAM, Mass.--(BUSINESS WIRE)--Alzheon, Inc. today announced the results from studies of ALZ-801 and its active molecule, tramiprosate. The new clinical data and analyses support Alzheon’s study design for the pivotal clinical program for ALZ-801, a first-in-class, oral amyloid-targeted medicine, in a genetically-defined population of patients at the Mild stage of Alzheimer’s disease (AD), with ongoing amyloid accumulation. In addition, the company presented clinical data with pharmacokinetic and pharmacodynamics analyses that support the dose selection of ALZ-801 for the pivotal study expected to initiate in 2017.
The pivotal program for ALZ-801 is distinguished in its design using a precision medicine approach to drug development for Alzheimer’s disease, targeting AD patients who are genetically-defined as homozygous for the ε4 allele of apolipoprotein E (APOE4/4 patients). The new clinical data and analyses are being presented by Alzheon in two oral presentations and two posters at the 13th International Conference on Alzheimer’s and Parkinson’s Disease (AD/PD™ 2017) which begins today in Vienna, Austria.
“Alzheon’s new insights are defining a more targeted and higher probability path for developing innovative medicines by directing Alzheimer’s R&D to the right patients, with the right drug, and at the right stage of their disease,” said Martin Tolar, MD, PhD, Founder, President and CEO of Alzheon. “We are pioneering a precision medicine approach to Alzheimer’s disease with our pivotal program for ALZ-801, by focusing on a well-recognized, genetically-defined subset of Alzheimer’s patients with the APOE4 genotype and by targeting patients at an early point in their disease progression, who have shown the greatest response to our lead molecule.”
Alzheon has completed the Phase 1 bridging program with ALZ-801, a novel prodrug of tramiprosate, and is presenting pharmacokinetic and safety data at the AD/PD conference supporting selection of the optimal dose of ALZ-801 that will be used in the upcoming confirmatory pivotal study:
- In the Phase 1b clinical studies of ALZ-801 conducted in healthy elderly volunteers, a tablet containing 265 mg of ALZ-801 administered twice daily demonstrated markedly improved pharmacokinetic properties, including steady target plasma levels with low inter-subject variability, and sustained plasma concentrations.
- ALZ-801 also showed improved gastrointestinal tolerability with lower incidence of nausea and vomiting compared to previous studies with oral tramiprosate.
- These results are being presented in a poster titled “ALZ-801 Brain Penetration, PK/PD Analyses and Clinical Dose Projection Form the Basis for Confirmatory Phase 3 Study in Alzheimer’s Disease.”
At the AD/PD conference, Alzheon is also presenting new clinical analyses for tramiprosate, the active molecule of prodrug ALZ-801. The new analyses evaluated AD patients in previous Phase 3 tramiprosate studies who were carriers of the homozygous APOE4/4 genotype, after segmenting them from the larger, all-comer study population involving more than 2,000 patients in North America and Europe. These analyses support the refinement of patient selection for the upcoming ALZ-801 studies to focus on APOE4/4 homozygous patients at the Mild stage of Alzheimer’s disease:
- The new analyses evaluated tramiprosate efficacy in APOE4/4 homozygous AD patients according to disease severity based on their Mini–Mental State Examination (MMSE) scores at baseline. The results showed tramiprosate’s largest efficacy signals in APOE4/4 homozygous patients with Mild AD, defined as MMSE of 22 to 26. These results are being presented in a poster titled “Tramiprosate Efficacy in APOE4 Homozygous Subjects with AD: Larger Effects in Mild Versus Moderate Patients.”
- For the first time, Alzheon will present safety and efficacy analyses from an extension study of AD patients who, after completing 78 weeks in the North American Phase 3 tramiprosate study, participated in an extension study and received an additional 52 weeks of treatment with the high dose of tramiprosate (150 mg twice daily). The safety profile of tramiprosate with exposures up to 130 weeks showed no new adverse events and was favorable.
- Efficacy data from the subgroup of APOE4/4 homozygous patients (N = 104) who enrolled in the extension study was analyzed over a total of 130 weeks. The results showed that APOE4/4 patients who received the high dose of tramiprosate over 130 weeks exhibited sustained cognitive and functional benefits, compared to patients who ‘crossed over’ from placebo in the 78-week study to receive tramiprosate for 52 weeks (the “delayed start point” for treatment) in the study.
- This clinical profile suggests a potential disease-modifying effect of tramiprosate, which is consistent with its beta amyloid anti-aggregation action and, specifically, effect on formation of toxic oligomers. This study will be presented as a late breaker oral session at AD/PD 2017 titled “Persistent Efficacy of Tramiprosate in APOE4 Homozygous AD Subjects Treated Over 130 Weeks: Results of North American Extension Study.”
“Our latest clinical analyses suggest that tramiprosate efficacy is highest in APOE4/4 homozygous AD patients at the Mild stage of disease, which is consistent with the findings from studies with other amyloid-targeted therapies. The potential for tramiprosate efficacy to be sustained over 130 weeks is also very encouraging,” said Susan Abushakra, MD, Chief Medical Officer of Alzheon. “These analyses have informed the selection criteria for the upcoming study of ALZ-801 in homozygous AD patients. With these promising efficacy data, the favorable long-term safety profile of tramiprosate, and the improved gastrointestinal tolerability of ALZ-801, we are poised to initiate the pivotal program with ALZ-801.”
In addition, Alzheon has been invited for a featured oral presentation in the AD/PD 2017 Forum on Translational Research in Drug Discovery for AD, given by Dr. Martin Tolar titled “ALZ-801: Efficient Alzheimer’s Disease Modification by Preventing Formation of Toxic Amyloid Aggregates.”
Alzheon, Inc. is committed to developing innovative medicines by directly addressing the underlying pathology of devastating neurodegenerative disorders. Our lead Alzheimer’s clinical candidate, ALZ-801, is a Phase 3-ready, first-in-class, small molecule oral inhibitor of amyloid aggregation and neurotoxicity – hallmarks of Alzheimer’s disease. ALZ-801 is a novel prodrug that builds on the safety and efficacy profile of the active compound tramiprosate, which has been evaluated in clinical trials involving over 2,000 Alzheimer’s patients. Our clinical expertise and technology platform is focused on developing drug candidates using a precision medicine approach based on individual genetic and biological information to advance therapies with the greatest impact for patients.