Latest news with #Alzheon
Business Wire
15-07-2025
- Health
- Business Wire
Alzheon to Present Insights into Oral Valiltramiprosate/ALZ-801 Mode of Action and Clinical Efficacy at
FRAMINGHAM, Mass.--(BUSINESS WIRE)-- 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. Share '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 30 th and will be available to all conference attendees, both in person at the Westin Harbor Castle in Toronto and virtually via the following link: 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 About ALZ-801 Valiltramiprosate/ALZ-801 is a potential first-in-class, investigational oral agent in Phase 3 development as a potentially disease-modifying treatment for AD. 1-5,7,10 Valiltramiprosate is designed to block the formation of neurotoxic soluble beta amyloid oligomers implicated in cognitive decline in Alzheimer's patients. 1-5,7,12 In mechanism of action studies, ALZ-801 has fully inhibited the formation of neurotoxic soluble beta amyloid oligomers at the Phase 3 clinical trial dose. 1,7,10,12 Valiltramiprosate acts through a novel enveloping molecular mechanism of action to block formation of neurotoxic soluble amyloid oligomers in the human brain 12 associated with the onset and progression of cognitive decline in AD patients. 1,2,5,7,8 Valiltramiprosate received Fast Track designation from the U.S. Food and Drug Administration in 2017 for Alzheimer's disease. In clinical trials, valiltramiprosate has shown potential for robust clinical efficacy and favorable safety results with no increased risk of brain vasogenic edema. 3-8,11,13 The initial Phase 3 program for valiltramiprosate is focusing on Early AD patients with two copies of the apolipoprotein ε4 allele (APOE4/4 homozygotes), with potential future program expansion to AD treatment and prevention in patients carrying one copy of the APOE4 gene and noncarriers. 1–8 Valiltramiprosate APOLLOE4 Phase 3 Trial An Efficacy and Safety Study of Valiltramiprosate in APOE4/4 Early Alzheimer's Disease Subjects (NCT04770220): This trial was designed to evaluate the efficacy, safety, biomarker and imaging effects of 265 mg twice daily oral dose of valiltramiprosate in Early AD subjects with two copies of the apolipoprotein ε4 allele (APOE4/4 homozygotes), who constitute approximately 15% of Alzheimer's patients. This double-blind, randomized trial compared oral valiltramiprosate to placebo treatment over 78 weeks. The APOLLOE4 trial was supported by a grant from the National Institute on Aging to Alzheon, with Susan Abushakra as the principal investigator. Valiltramiprosate APOLLOE4 Long Term Extension Trial (LTE) An ongoing long-term extension of the trial, APOLLOE4-LTE evaluates valiltramiprosate in subjects who complete the core APOLLOE4 study for an additional 104 weeks of treatment for a total of 182 weeks or 3.5 years over the core and LTE study. This LTE study is currently ongoing in the US, UK and Canada (NCT06304883). Valiltramiprosate Phase 2 Biomarker Trial Biomarker Effects of Valiltramiprosate in APOE4 Carriers with Early Alzheimer's Disease (NCT04693520): This trial was designed to evaluate the effects of 265 mg twice daily oral dose of valiltramiprosate on biomarkers of AD pathology in subjects with Early AD, who have either the APOE4/4 or APOE3/4 genotype and constitute 65-70% of Alzheimer's patients. The primary outcome is the change from baseline in plasma p-tau 181. The trial also included evaluation of clinical efficacy, safety, tolerability, and pharmacokinetic profile of valiltramiprosate over 104 weeks of treatment. An ongoing long-term extension of the trial evaluates the same dose of valiltramiprosate for an additional 104 weeks of treatment for a total of 208 weeks 1,5,6. About Alzheon Alzheon, Inc. is a clinical-stage biopharmaceutical company developing a broad portfolio of product candidates and diagnostic assays for patients suffering from Alzheimer's disease and other neurodegenerative disorders. We are committed to developing innovative medicines by directly addressing the underlying pathology of neurodegeneration. Our lead Alzheimer's clinical candidate, valiltramiprosate/ALZ-801, is a first-in-class oral agent in Phase 3 development as a potentially disease-modifying treatment for AD. Valiltramiprosate is an oral small molecule that has been observed to fully block the formation of neurotoxic soluble amyloid oligomers in preclinical tests. Our clinical expertise and technology platform are focused on developing drug candidates and diagnostic assays using a precision medicine approach based on individual genetic and biomarker information to advance therapies with the greatest impact for patients. Alzheon Scientific Publications 1 Pearson D, et al: 2025. 2 Hey JA, et al: Clinical Pharmacokinetics of Oral ALZ-801/Valiltramiprosate in a Two-Year Phase 2 Trial of APOE4 Carriers with Early Alzheimer's Disease, Clinical Pharmacokinetics 2025. 3 Aye S, et al: Point of View: Challenges in Implementation of New Immunotherapies for Alzheimer's Disease, The Journal of Prevention of Alzheimer's Disease 2025;12(1):100022. 4 Abushakra S, et al: APOLLOE4 Phase 3 Study of Oral ALZ-801/Valiltramiprosate in APOE ε 4/ ε 4 Homozygotes with Early Alzheimer's Disease: Trial Design and Baseline Characteristics, Alzheimer's & Dementia 2024; 10(3): e12498. 5 Tolar M, et al: The Single Toxin Origin of Alzheimer's Disease and Other Neurodegenerative Disorders Enables Targeted Approach to Treatment and Prevention, International Journal of Molecular Sciences 2024; 25(5), 2727. 6 Hey JA, et al: Analysis of Cerebrospinal Fluid, Plasma β Amyloid Biomarkers, and Cognition from a 2-Year Phase 2 Trial Evaluating Oral ALZ-801/Valiltramiprosate in APOE4 Carriers with Early Alzheimer's Disease Using Quantitative Systems Pharmacology Model, Drugs 2024; 84(7), 825-839. 7 Hey JA, et al: Effects of Oral ALZ-801/Valiltramiprosate on Plasma Biomarkers, Brain Hippocampal Volume, and Cognition: Results of 2-Year Single Arm, Open Label, Phase 2 Trial in APOE4 Carriers with Early Alzheimer's Disease, Drugs 2024; 84(7), 811-823. 8 Tolar M, et al: Neurotoxic Soluble Amyloid Oligomers Drive Alzheimer's Pathogenesis and Represent a Clinically Validated Target for Slowing Disease Progression, International Journal of Molecular Sciences 2021; 22(12), 6355. 9 Abushakra S, et al: 2020; 6(1): e12117. 10 Tolar M, et al: Aducanumab, Gantenerumab, BAN2401, and ALZ-801—the First Wave of Amyloid-Targeting Drugs for Alzheimer's Disease with Potential for Near Term Approval, Alzheimer's Research & Therapy 2020; 12(1): 95. 11 Tolar M, et al: The Path Forward in Alzheimer's Disease Therapeutics: Reevaluating the Amyloid Cascade Hypothesis, Alzheimer's & Dementia 2020; 16(11):1553-1560. 12 Hey JA, et al: 2018; 32(9): 849-861. 13 Hey JA, et al: Clinical Pharmacokinetics and Safety of ALZ-801, a Novel Prodrug of Tramiprosate in Development for the Treatment of Alzheimer's Disease, Clinical Pharmacokinetics 2018; 57(3): 315-333. 14 Abushakra S, et al: 2017; 4(3): 149-156. 15 Kocis P, et al: 2017; 31(6): 495-509. 16 Abushakra S, et al: 2016; 3(4): 219-228.
Yahoo
11-04-2025
- Health
- Yahoo
Alzheon's Alzheimer's pill fails in Phase III trial
US-based Alzheon's Alzheimer's disease pill has failed in a Phase III trial, but the biopharma still holds hope for the drug after seeing signals in a subgroup of patients. The company said that while valiltramiprosate did not meet the primary endpoint in the pivotal APOLLOE4 study, nominally statistically significant and clinically meaningful cognitive benefits were observed in Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog13), in a prespecified group of patients who could benefit from early intervention. ADAS-Cog13 is a 13-item version of a scale used to assess cognitive function in patients with Alzheimer's disease, with higher scores indicating greater cognitive impairment. The global APOLLOE4 study (NCT04770220) enrolled 325 patients with early Alzheimer's disease who are homozygous for the ε4 allele of the apolipoprotein gene (APOE4/4). Patients were randomised to receive twice daily, oral valiltramiprosate or placebo over 78 weeks. The trial's primary endpoint was ADAS-Cog13, with key secondary endpoints being the Clinical Dementia Rating–Sum of Boxes (CDR-SB) and Amsterdam-Instrumental Activities of Daily Living (A-IADL). Investigators also measured hippocampal volume as the main imaging outcome and fluid biomarkers as additional outcomes. In the overall population, the APOLLOE4 study did not meet the primary endpoint of slowing cognitive decline as assessed by ADAS-Cog13, with an 11% improvement in the treatment arm. However, a prespecified analysis in patients at the mild cognitive impairment stage of Alzheimer's disease showed nominally statistically significant cognitive benefits of 52% as measured by ADAS-Cog13. The data also showed clinically meaningful functional effects of 102% as measured by CDR-SB and 96% benefit on the Disability Assessment for Dementia (DAD). The company has not confirmed its regulatory plans for Alzheon's Alzheimer's drug based on the Phase III data. GlobalData's managing neurology analyst Pippa Salter comments: 'Given the APOLLOE4 results, it remains to be seen whether Alzheon will pursue regulatory approval for early Alzheimer's disease or if it will pivot to just the MCI patient population. "There is also the potential for expansion as Alzheon plans to evaluate valiltramiprosate in additional patient populations, with prevention in APOE4 homozygotes a promising option since the results of the APOLLOE4 trial showed that valiltramiprosate was more effective the earlier in the disease it was administered.' Regarding safety, the Phase III Alzheimer's trial reported no increased risk of vasogenic brain oedema or microhaemorrhages described as amyloid-related imaging abnormalities (ARIA-E, ARIA-H) with Alzheon's drug. ARIA has been a safety issue associated with approved amyloid-targeting Alzheimer's disease therapies. Both Eli Lilly's Kisunla (donanemab) and Biogen and Eisai's Leqembi (lecanemab) have reported ARIA incidents, with these both being points of contention with agencies ahead of their relative approvals. Lilly's drug was approved by the US Food and Drug Administration (FDA) in July 2024 for use in patients with mild cognitive impairment or dementia stage of disease. The drug carries a boxed warning about the risk of ARIA. Meanwhile, the European Medicines Agency (EMA) has recommended the rejection of the drug for marketing authorisation in the EU due to the risk of ARIA events not being outweighed by the therapy's benefit. Kisunla received approval in the UK in October 2024. On the same day of its UK approval, the National Institute for Health and Care Excellence (NICE) announced it would not be covering Kisunla for use in the UK's National Health Service (NHS) due to the unfavourable risk-benefit profile and poor cost-effectiveness. Biogen and Eisai's drug made it to the market earlier, gaining FDA-accelerated approval in January 2023. After the Phase III readout, full approval was confirmed by the FDA in June 2023. In January 2025, the company submitted a new application to the agency seeking approval for a subcutaneous version of the drug. In November 2024, the EMA recommended the approval of Leqembi, three months after the UK granted the therapy's approval. Again, NICE has not approved the drug for use on the NHS due to its benefit being too small to justify its cost. Before Leqembi, Biogen and Eisai gained approval for another anti-amyloid Alzheimer's therapy, Aduhelm (aducanumab). This has since been removed from the market due to Biogen wanting to focus on Leqembi. GlobalData predicts the Alzheimer's disease market will reach $19.3bn across the eight major markets (8MM: US, France, Germany, Italy, Spain, UK, Japan, and China) by 2033. GlobalData is the parent company of Clinical Trials Arena. "Alzheon's Alzheimer's pill fails in Phase III trial" was originally created and published by Clinical Trials Arena, a GlobalData owned brand. The information on this site has been included in good faith for general informational purposes only. It is not intended to amount to advice on which you should rely, and we give no representation, warranty or guarantee, whether express or implied as to its accuracy or completeness. You must obtain professional or specialist advice before taking, or refraining from, any action on the basis of the content on our site. Sign in to access your portfolio
