Valiltramiprosate Evaluated in APOLLOE4 Trial, First Interventional Phase 3 Alzheimer’s Trial Focused on High-Risk APOE4/4 Homozygotes
Anti-Amyloid Oligomer Action Underpins Valiltramiprosate’s Potential Benefit in Alzheimer’s Disease at MCI Stage of Disease
Valiltramiprosate Designed to Inhibit Amyloid Aggregation by Distinct Upstream Mode of Action to Slow Progression of Alzheimer’s Disease
Precision Medicine Approach Supported by Valiltramiprosate’s Favorable Safety in High-Risk APOE4 Carriers with Major Unmet Medical Need
Valiltramiprosate Has Potential to Become the First Oral Agent to Slow Alzheimer’s Pathology in Patients
Alzheon, Inc., a clinical-stage biopharmaceutical company developing a broad portfolio of investigational therapies and diagnostic assays for patients with Alzheimer’s disease (AD) and other neurodegenerative disorders, today announced it will present new data on its lead investigational product, valiltramiprosate, highlighting the differentiated mode of action that acts upstream in the amyloid pathway, blocking formation of neurotoxic amyloid oligomers that drive disease progression. Valiltramiprosate showed positive clinical and volumetric MRI effects in patients with Mild Cognitive Impairment (MCI) who carry one or two copies of the ε4 allele of the apolipoprotein E gene (APOE3/4 heterozygotes and APOE4/4 homozygotes, respectively). The first of-its-kind data will be presented in a symposium during the Alzheimer’s Association International Conference (AAIC) in Toronto, Canada.
“Valiltramiprosate represents a promising advancement in targeting the early highly toxic forms of beta amyloid that drive Alzheimer’s disease onset and progression,” said Sam Gandy, M.D., Ph.D., Professor of Neurology and Psychiatry at Icahn School of Medicine at Mount Sinai. “By focusing on oligomer formation upstream, this oral therapy has the potential to change the treatment paradigm for patients at risk for Alzheimer’s and those with early symptomatic disease, particularly the high-risk APOE4 carriers.”
Valiltramiprosate is an investigational oral AD treatment in Phase 3 clinical development with an upstream mechanism of action from anti-amyloid antibodies that prevents formation of neurotoxic amyloid oligomers. A prodrug of tramiprosate with optimized pharmacokinetics and brain penetration, valiltramiprosate was designed to prevent amyloid aggregation at the initial stage of the amyloid cascade. Soluble amyloid oligomers play a central role in the pathogenesis and progression of Alzheimer’s disease.
“Results from the APOLLOE4 Phase 3 trial evaluating valiltramiprosate showed promising clinical and volumetric MRI effects in Alzheimer’s patients with the APOE4/4 genotype at the earliest symptomatic stage of disease. With a mechanism of action directly blocking the formation of neurotoxic beta amyloid oligomers, valiltramiprosate addresses the upstream pathology of Alzheimer’s disease and offers a potential safe, effective, and accessible oral treatment,” said John Hey, PhD, Chief Scientific Officer of Alzheon. “These findings reinforce our understanding of how valiltramiprosate works at the molecular level and provide a mechanistic foundation for the positive clinical, fluid biomarker and imaging outcomes observed in our Phase 2 and Phase 3 studies in APOE4 carriers and homozygotes, respectively, with early symptomatic AD.”
Preclinical and clinical studies demonstrate that valiltramiprosate interacts with monomeric beta amyloid and prevents the formation of soluble oligomers that drive synaptic toxicity and neuronal loss. Quantitative systems pharmacology (QSP) analysis further supports the clinical relevance of this mechanism of action by linking reductions in formation of toxic amyloid oligomers to preservation of hippocampal volume, attenuation of neurodegeneration in all brain regions, and slowing of disease progression. These effects are most pronounced in the high risk APOE4/4 population, which has a high burden of neurotoxic amyloid oligomers.
These clinical and biomarker results support Alzheon’s precision medicine approach of focusing on high-risk APOE4 carriers with Alzheimer’s disease, and provide the scientific rationale for targeting beta amyloid oligomers upstream in the disease process and at the early symptomatic stages of AD.
Details of Symposium at AAIC 2025
The symposium will be held in the afternoon on July 30th and will be available to all conference attendees, both in person at the Westin Harbor Castle in Toronto and virtually via the following link: https://aaic.alz.org/program/schedule.asp#a06
Title: Inhibition of Beta Amyloid Oligomer Neurotoxicity with Oral Valiltramiprosate
Date and Time: Wednesday, July 30, 12:30 p.m. local Toronto time (ET)
Location: Westin Harbor Castle, Frontenac Ballroom
Symposium Chair & Moderator:
- Sharon Cohen, M.D., FRCPC, Medical Director, Toronto Memory Program, Toronto, ON, Canada
Presenters:
- Samuel Gandy, M.D., Ph.D., Professor of Neurology and Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Kenjiro Ono, M.D., Ph.D., Department of Neuropathology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Huge Geerts, M.D., Ph.D., Head of Neuroscience Modeling, Quantitative Systems Pharmacology, Certara, Berwyn, PA, USA
- John Hey, Ph.D., Chief Scientific Officer, Alzheon, Inc. Framingham, MA, USA
In addition, Alzheon scientists will be provide clinical and imaging analyses from the APOLLOE4 Phase 3 study of valiltramiprosate in APOE4/4 homozygotes in eight poster presentations at the conference:
Poster: “Quantitative Systems Pharmacology Analysis of Hippocampal Volume Trajectory by APOE Genotype and Neuroprotective Effects of Valiltramiprosate/ALZ-801 in Early AD”
- Presenter: Dr. Hugo Geerts, Head of Neuroscience Modeling, Quantitative Systems Pharmacology, Certara, Berwyn, PA, USA
- Poster #108550
Poster: “Efficacy and Safety of Oral Valiltramiprosate in APOE4/4 Homozygotes with Early AD: Topline Results from the APOLLOE4 Phase 3 Trial”
- Presenter: Dr. Aidan Power, Chief Development Officer, Alzheon, Inc.
- Poster #108821
Poster: “Safety and ARIA Results of the Oral Anti-Amyloid Agent Valiltramiprosate from the Phase 3 APOLLOE4 Trial in APOE4/4 Homozygotes with Early AD”
- Presenter: Dr. Patrick Kesslak, Senior Research Fellow, Alzheon, Inc.
- Poster #108685
Poster: “Correlations of Valiltramiprosate Effects on Hippocampal Volume and Cortical Thickness with Clinical Outcomes in the Pre-Specified MCI Group: Subgroup Analysis from the 78-Week APOLLOE4 Phase 3 Trial in APOE4/4 Homozygotes”
- Presenter: Dr. Susan Abushakra, Chief Medical Officer, Alzheon, Inc.
- Poster #108827
Poster: “Valiltramiprosate Effects on Microstructural Integrity of Grey and White Matter in APOE4/4 Homozygotes with Early AD and their Correlations to Clinical Outcomes: MRI Mean Diffusivity Results from the 78-Week APOLLOE4 Phase 3 Trial”
- Presenter: Dr. Earvin Liang, Vice President of Clinical Development, Alzheon, Inc.
- Poster #108716
Poster: “Quantitative Systems Pharmacology Analysis of Oral Valiltramiprosate/ALZ-801 Predicts Slowing of Alzheimer’s Disease Progression by Anti-Amyloid Oligomer and APOE4 Structural Corrector Modes of Action”
- Presenter: Jean Schaefer, Vice President of CMC & Project Management, Alzheon, Inc.
- Poster #108561
Poster: “Valiltramiprosate/ALZ-801 Prevents Hippocampal Atrophy and Clinical Decline in a Stage 2 AD Subpopulation in APOLLOE4 Phase 3 Study”
- Presenter: Dr. Jeremy Yu, Senior Clinical Research Fellow, Alzheon, Inc.
- Poster #108565
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