Fully Enrolled Pivotal APOLLOE4 Phase 3 Trial in Early Alzheimer's Patients on Track for Topline Data Readout and Initiation of NDA Submission in 2024
ALZ-801 Tablet Inhibits Formation of Soluble Toxic Amyloid Aggregates and Acts Upstream from All Late-Stage Amyloid Targeting Treatments
Robust and Sustained P-tau181 Reduction in Plasma, Combined with Preservation of Brain Volume and Positive Correlations with Cognitive Effects, Reinforces Potential of ALZ-801 to Slow Alzheimer's Disease Progression
ALZ-801 Safety Results Remain Favorable Consistent with Prior Formulation's Data Resulting in Safety Database of Over 3,000 AD Patient, Showing no Increased Risk of Vasogenic Brain Edema
Alzheon, Inc., a clinical-stage biopharmaceutical company developing a broad portfolio of product candidates and diagnostic assays for patients suffering from Alzheimer's disease (AD) and other neurodegenerative disorders, today announced its participation in the Nobel Forum "Challenges for Implementation of New Alzheimer's Disease Treatments" covering Alzheimer's therapeutics for the future, at the Karolinska Institute in Stockholm, Sweden from January 18-19.
Alzheon Founder, President, and CEO, Martin Tolar, MD, PhD, will present an overview of investigational oral ALZ-801/valiltramiprosate anti-amyloid oligomer treatment program in the section "Optimal Treatment for Future Combination Therapy?" moderated by Kaj Blennow, MD, PhD, on January 19 at 1:30 PM CET (7:30 AM EST).
"We are honored to have received an invitation to present at the prestigious Nobel Forum and discuss how ALZ-801 tablet could help shape the future therapeutic landscape for Alzheimer's disease. Alzheon's simplified approach with an oral tablet has an opportunity to transform the standard of care for millions of patients," said Martin Tolar, MD, PhD, Founder, President, and CEO of Alzheon. "ALZ-801 efficacy data and a favorable safety profile, showing no increased risk of vasogenic edema, underscore the differentiated clinical profile of the treatment. The growing body of evidence continues to support ALZ-801's potential as the first oral anti-amyloid disease modifying therapy for Alzheimer's disease, and we are excited about the potential of ALZ-801 to improve access to treatment for patients around the world."
ALZ-801/valiltramiprosate is an investigational oral therapeutic candidate in Phase 3 development for the treatment of Early AD. In mechanism of action studies, ALZ-801 fully blocked the formation of neurotoxic soluble beta amyloid oligomers at the Phase 3 clinical dose. ALZ-801 has shown treatment potential in the highest-risk and most fragile Alzheimer's population patients with two copies of the apolipoprotein e4 allele (APOE4/4 homozygotes), as well as positive safety results, with no increased risk of vasogenic brain edema. This population is the focus of Alzheon's pivotal 78-week APOLLOE4 Phase 3 trial, which is now fully enrolled, and topline data are expected in the third quarter of 2024.
Last year, Alzheon's Phase 2 open-label biomarker trial completed the core portion of the study over 104 weeks of treatment and achieved its primary endpoint. The trial evaluated biomarker effects, clinical efficacy, and safety of ALZ-801 tablet in 84 Early AD patients, who carry either one or two copies of the e4 allele of apolipoprotein E gene (APOE3/4 heterozygotes and APOE4/4 homozygotes, respectively), and who showed positivity for amyloid and tau in cerebrospinal fluid. Subjects in the Phase 2 study showed a statistically significant reduction in p-tau181, a core biomarker of neuronal damage, stabilization of cognition following two years of treatment, and a reduction in hippocampal atrophy compared to an external control arm in a matched real-world data analysis.
About ALZ-801
ALZ-801/valiltramiprosate is an investigational oral agent in Phase 3 development as a potentially disease modifying treatment for AD.1,3 ALZ-801 is designed to block the formation of neurotoxic soluble beta amyloid oligomers causing cognitive decline in Alzheimer's patients. In mechanism of action studies, ALZ-801 has fully inhibited the formation of neurotoxic soluble beta amyloid oligomers at the Phase 3 clinical dose.5,6 ALZ-801 acts through a novel enveloping molecular mechanism of action to fully block formation of neurotoxic soluble amyloid oligomers in the human brain7 associated with the onset and progression of cognitive decline in AD patients.1-4 ALZ-801 received Fast Track designation from the U.S. Food and Drug Administration in 2017 for Alzheimer's disease. In clinical trials, ALZ-801 has shown favorable safety results.5-7,9 The initial Phase 3 program for ALZ-801 is focusing on Early AD patients with the APOE4/4 genotype, with potential future program expansion to AD treatment and prevention in patients carrying one copy of the APOE4 gene and noncarriers.1-4
ALZ-801 Phase 2 Biomarker Trial
Biomarker Effects of ALZ-801 in APOE4 Carriers With Early Alzheimer's Disease (NCT04693520): This ongoing trial was designed to evaluate the effects of 265 mg twice daily oral dose of ALZ-801 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 trial also included evaluation of clinical efficacy, safety, tolerability, and pharmacokinetic profile of ALZ-801 over 104 weeks of treatment. An ongoing long-term extension of the trial evaluates ALZ-801 for an additional 52 weeks of treatment for a total of 156 weeks.
ALZ-801 APOLLOE4 Phase 3 Trial
An Efficacy and Safety Study of ALZ-801 in APOE4/4 Early Alzheimer's Disease Subjects (NCT04770220): This ongoing trial is designed to evaluate the efficacy, safety, biomarker and imaging effects of 265 mg twice daily oral dose of ALZ-801 in Early AD subjects with two copies of the apolipoprotein e4 allele (APOE4/4 homozygotes), who constitute approximately 15% of Alzheimer's patients. This is a double-blind, randomized trial comparing oral ALZ-801 to placebo treatment over 78 weeks. The APOLLOE4 trial is supported by a $51 million grant from the National Institute on Aging.
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, ALZ-801/valiltramiprosate, is an oral agent in Phase 3 development as a potentially disease modifying treatment for AD. ALZ-801is 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 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, 6355.
2 Abushakra S, et al: APOE e4/e4 Homozygotes with Early Alzheimer's Disease Show Accelerated Hippocampal Atrophy and Cortical Thinning that Correlates with Cognitive Decline, Alzheimer's Dementia, 2020; 6: e12117.
3 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: 95.
4 Tolar M, et al: The Path Forward in Alzheimer's Disease Therapeutics: Reevaluating the Amyloid Cascade Hypothesis, Alzheimer's Dementia, 2019; 1-8.
5 Hey JA, et al: Discovery and Identification of an Endogenous Metabolite of Tramiprosate and Its Prodrug ALZ-801 that Inhibits Beta Amyloid Oligomer Formation in the Human Brain, CNS Drugs, 2018; 32(9): 849-861.
6 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.
7 Abushakra S, et al: Clinical Effects of Tramiprosate in APOE4/4 Homozygous Patients with Mild Alzheimer's Disease Suggest Disease Modification Potential, Journal of Prevention of Alzheimer's Disease, 2017; 4(3): 149-156.
8 Kocis P, et al: Elucidating the Aß42 Anti-Aggregation Mechanism of Action of Tramiprosate in Alzheimer's Disease: Integrating Molecular Analytical Methods, Pharmacokinetic and Clinical Data, CNS Drugs, 2017; 31(6): 495-509.
9 Abushakra S, et al: Clinical Benefits of Tramiprosate in Alzheimer's Disease Are Associated with Higher Number of APOE4 Alleles: The "APOE4 Gene-Dose Effect," Journal of Prevention of Alzheimer's Disease, 2016; 3(4): 219-228.
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Contacts:
Media
Adem Albayrak
Alzheon, Inc.
508.861.7709
adem.albayrak@alzheon.com
