Breakthroughs in Alzheimer Research Pave Way for New Era of Treatment: Martin Tolar, MD, PhD

WATCH TIME: 12 minutes

“The distinction between dementia and Alzheimer has been very difficult. The old diagnosis, which was based on collective symptoms, was about 30% wrong and has been a big problem for drug development.”

ALZ-801 (Alzheon), an investigational disease-modifying therapy for Alzheimer disease (AD), is designed to inhibit amyloid oligomer formation which is a key driver of the disease. This treatment has the potential to be different from other therapies for AD because of its novel mechanism of action and oral mode of administration. Recently, Alzheon announced the initiation of patient dosing in an open-label extension of its pivotal, double-blind, randomized phase 3 APOLLOE4 trial (NCT04770220).¹ The trial, which is a follow-up to the company’s successful phase 2 biomarker study (NCT04693520), is fully enrolled with topline data anticipated in the third quarter of 2024.

APOLLOE4 is designed to assess the efficacy, safety, biomarker, and imaging effects of 265 mg twice daily oral dose of ALZ-801 in 325 patients with early AD who have 2 copies of the apolipoprotein ε4 allele (APOE4/4 homozygotes). The 78-week study will primarily assess effects on cognition, determined using the Alzheimer’s Disease Assessment Scale-cognitive subscale, as the primary end point. The phase 3 study also includes several notable secondary end points that evaluate aspects of function, activities of daily living, and neuropsychiatric symptoms. In addition, investigators will also observe treatment effects on fluid and imaging biomarkers, similar to the previously completed phase 2 study.

Martin Tolar, MD, PhD, the founder, president and CEO at Alzheon, recently sat down with NeurologyLive^® in an interview to discuss the key biological discoveries that have advanced the understanding of AD from his clinical and scientific perspective. He also talked about the important role that biomarkers, such as the APOE4 genotype, play in tracking the progression of the disease and the efficacy of treatments among patients with AD. Furthermore, he spoke about the challenges and potential benefits of developing oral treatments for Alzheimer based on the research that is currently going on in the company with ALZ-801.

REFERENCES
1. Alzheon announces first patient dosed in long-term extension of APOLLOE4 phase 3 trial of oral ALZ-801/valiltramiprosate and launches 52-week extension of phase 2 biomarker trial in patients with early Alzheimer’s disease. News release. Alzheon. April 30, 2024. Accessed June 10, 2024. https://www.biospace.com/article/releases/alzheon-announces-first-patient-dosed-in-long-term-extension-of-apolloe4-phase-3-trial-of-oral-alz-801-valiltramiprosate-and-launches-52-week-extension-of-phase-2-biomarker-trial-in-patients-with-early-alzheimer-s-disease/