Early Biomarker Evaluation and Cognitive Stabilization in Alzheimer Treatment: Martin Tolar, MD, PhD

WATCH TIME: 10 minutes

"The APOE4 genotype specifically impairs the clearance for amyloid through the RP1 receptor, and the patients with 2 copies will almost all have the brain pathology by age 65 and most will have clinical disease."

ALZ-801 (Alzheon) is an investigational oral disease-modifying therapy in development for the treatment of early Alzheimer disease (AD). In prior studies, ALZ-801 has shown both potential for clinical efficacy in the highest-risk and most fragile Alzheimer population, patients with 2 copies of the apolipoprotein ε4 allele (APOE4/4 homozygotes), and favorable safety with no increased risk of vasogenic brain edema. This patient population is the focus of Alzheon’s pivotal 78-week APOLLOE4 phase 3 trial (NCT04770220), which is the company noted is fully enrolled and expects topline data in the third quarter of 2024.¹

The previously completed phase 2 study (NCT04693520) assessing ALZ-801 in APOE4 carriers with early AD achieved its primary efficacy end point of reduction in plasma p-tau181 over 2 years.^2,3 Published in Drugs, a significant 31% reduction (P = .045) in plasma p-tau181 was reported at 13 weeks and sustained at every visit through 104 weeks. Notably, memory scores showed improvement from baseline at 26 weeks and continued to display minimal decline from baseline at 104 weeks. Additional findings showed that these cognitive effects were significantly associated with decreased hippocampal volume atrophy (P = .002).

Martin Tolar, MD, PhD, the founder, president and CEO at Alzheon, recently sat down with NeurologyLive® in an interview to discuss the most notable takeaways for the clinician community from the phase 2 data such as how the treatment impacts brain volume and phosphorylated tau levels in patients. He also talked about the main outcomes and measures being evaluated in the ongoing placebo-controlled phase 3 study. Furthermore, Tolar spoke about how the APOE4 genotype affects the progression and treatment response in patients with AD.

REFERENCES
1. A Two Peer-Reviewed Scientific Publications Describe Fluid Biomarker, Brain Preservation and Clinical Benefits Following 2 Years of Treatment in Phase 2 Trial Evaluating Oral ALZ-801/Valiltramiprosate in APOE4 Carriers with Early Alzheimer’s Disease. News release. Alzheon. June 25, 2024. Accessed July 19, 2024. https://alzheon.com/two-peer-reviewed-scientific-publications-describe-fluid-biomarker-brain-preservation-and-clinical-benefits-following-2-years-of-treatment-in-phase-2-trial-evaluating-oral-alz-801-valiltramiprosate-i/
2. Hey JA, Abushakra S, Blennow K, 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. Published online June 20, 2024. doi:10.1007/s40265-024-02067-8
3. Hey JA, Yu JY, Abushakra S, 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. Published online June 20, 2024. doi:10.1007/s40265-024-02068-7