New Data Shows Significantly Higher Rate of Cortical Thickness Loss in Early Alzheimer’s Patients with APOE4/4 Genotype
Cortical Thickness May Be a Useful Biomarker in Future Disease Modification Trials with High-Risk APOE4/4 Alzheimer’s Patients
FRAMINGHAM, Mass., December 2, 2019 – Alzheon, Inc., a clinical-stage biopharmaceutical company focused on developing new medicines for patients suffering from Alzheimer’s disease (AD) and other neurodegenerative disorders, announced today that scientific poster #P59, APOE4/4 Subjects with Early Alzheimer’s Disease Show Accelerated Loss of Cortical Thickness and Cognitive Decline Compared to APOE3/3 Subjects, is scheduled for presentation on December 5, 2019, at 3:30 p.m. local time in Poster Session Theme 3: Clinical Trials Imaging, at the CTAD conference in San Diego, USA. Click to view the poster
In this study, Alzheon researchers analysed clinical and MRI imaging datasets from the AD Neuroimaging Initiative 1 (ADNI-1): late Mild Cognitive Impairment (MCI) and Mild AD groups – collectively called “Early AD” – to compare patients homozygous for the apolipoprotein e4 allele (APOE4/4) to those with APOE3/3 genotype. The rate of cortical thickness loss was shown to be significantly higher in Early AD patients with the APOE4/4 genotype. Cortical thickness loss also showed significant correlation to cognitive decline at the MCI stage. Therefore, cortical thinning could be a valuable imaging biomarker in future trials of APOE4/4 subjects who are at risk of early disease progression.
“Individuals with the APOE4/4 genotype are known to have an earlier onset of Alzheimer’s symptoms and smaller hippocampus volumes compared to those with the APOE3/3 genotype. This new study shows that they also have faster loss of cortical thickness, which correlates with more rapid cognitive decline at the early stages of disease,” said Anton P. Porsteinsson, MD, the William B. and Sheila Konar Professor of Psychiatry, Neurology, Neuroscience, and Medicine and Director, Alzheimer’s Disease Care, Research and Education Program (AD-CARE) at the University of Rochester School of Medicine and Dentistry in Rochester, NY. “Therefore, cortical thickness may be a useful structural biomarker and complementary to hippocampus volume for future disease modification drug trials in APOE4/4 patients.”
Alzheon’s lead product candidate, ALZ-801, was designed to achieve high brain levels with oral administration to fully inhibit the formation of toxic soluble amyloid oligomers, with little effect on the other forms of amyloid that may be necessary for brain health. ALZ-801 oral tablet shows a favorable long-term safety profile, with no reports of vasogenic edema, and received Fast Track designation from the U.S. Food and Drug Administration (FDA). Building upon the clinical validation from intravenous anti-amyloid antibodies aducanumab and BAN2401, which showed the therapeutic efficacy of targeting toxic beta amyloid oligomers, Alzheon intends to launch the Phase 3 trial with ALZ-801 oral tablet in 2020.
“This study further supports the distinct biological phenotype of Alzheimer’s subjects with the APOE4/4 genotype. We plan to include this additional marker of disease progression in the Phase 3 trial of ALZ-801, our oral agent that can robustly inhibit amyloid oligomer formation at the planned clinical dose,” said Susan Abushakra, MD, Chief Medical Officer of Alzheon. “Alzheon’s 78-week Phase 3 trial will enroll APOE4/4 patients with Early Alzheimer’s disease, and will include multiple CSF, plasma and imaging biomarkers assessments. Together with the expected cognitive effects, positive effects on hippocampus atrophy and/or cortical thinning would support the disease modifying effect of ALZ-801.”
Alzheon’s lead product candidate, ALZ-801, an oral anti-amyloid drug candidate that is an optimized prodrug of tramiprosate, has shown promising results in analyses of clinical data1,2 and a novel therapeutic mechanism of action.3 ALZ-801 has received Fast Track designation from the U.S. Food and Drug Administration. The clinical data for ALZ-8014 and its active agent, tramiprosate, suggest long-term clinical efficacy in AD patients with the apolipoprotein e4 (APOE4) genotype and a favorable safety profile.1,2 ALZ-801 acts through a novel enveloping molecular mechanism of action blocking the formation of toxic amyloid oligomers3 associated with the development and progression of AD.6 The cognitive improvements observed in AD patients in the tramiprosate Phase 3 studies may be attributed, in part, to the therapeutic effects of 3-sulfopropanoic acid (3-SPA), an endogenous substance in the human brain, discovered by Alzheon scientists, that inhibits the formation of neurotoxic beta amyloid oligomers.5 3-SPA is the primary metabolite of ALZ-801 in humans and its discovery elucidates the beneficial pharmaceutical attributes of ALZ-801, including a favorable safety profile, selectivity against beta amyloid oligomers, and excellent brain penetration. ALZ-801 increases levels of 3-SPA in the brain and augments the body’s natural mechanism for blocking the formation of toxic amyloid oligomers.5 The initial Phase 3 program for ALZ-801 will focus on patients with the homozygous APOE4/4 genotype at the Early stage of AD, with the potential for future expansion to additional Alzheimer’s populations.6
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 beta 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 are 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.
1 Abushakra et al. Journal of Prevention of Alzheimer’s Disease, 2016
2 Abushakra et al. Journal of Prevention of Alzheimer’s Disease, 2017
3 Kocis et al. CNS Drugs, 2017
4 Hey et al. Clinical Pharmacokinetics, 2018
5 Hey et al. CNS Drugs, 2018
6 Tolar et al. Alzheimer’s & Dementia, 2019
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