Alzheon Study on ALZ-801 in APOE4/4 Early Alzheimer's Published

Alzheon, Inc., a clinical-stage biopharmaceutical company based in Framingham, Massachusetts, has made significant strides in the treatment of Alzheimer’s disease (AD) with its latest scientific publication. This research details the APOLLOE4 Phase 3 study, a pioneering trial aimed at AD patients who carry two copies of the apolipoprotein ε4 allele (APOE4/4 homozygotes). This subgroup of patients has a critically high risk of developing Alzheimer’s, often a decade earlier than the general population, and currently lacks effective treatment options.

The publication, titled “APOLLOE4 Phase 3 Study of Oral ALZ-801/Valiltramiprosate in APOE ε4/ε4 Homozygotes with Early Alzheimer’s Disease: Trial Design & Baseline Characteristics,” appears in the journal Alzheimer’s & Dementia Translational Research & Clinical Interventions. According to Martin Tolar, MD, PhD, Founder, President, and CEO of Alzheon, this 13th publication by the company underscores their dedication to advancing treatments for Alzheimer’s patients, especially those most vulnerable like APOE4/4 homozygotes. These individuals represent about 15% of Alzheimer’s patients globally and face a dire need for safe treatments that can halt disease progression.

ALZ-801, also known as valiltramiprosate, is an investigational oral therapy in Phase 3 development for early-stage AD. It works by completely blocking the formation of neurotoxic beta-amyloid oligomers, which are believed to trigger cognitive decline in Alzheimer’s patients. The APOLLOE4 Phase 3 trial, which spans 78 weeks, focuses on testing the efficacy and safety of ALZ-801. Topline results from this trial are expected by late 2024.

In line with current diagnostic criteria, Alzheimer’s disease is divided into preclinical, mild cognitive impairment (MCI), and dementia stages. The APOLLOE4 study is a randomized, double-blind, placebo-controlled, parallel-arm trial conducted at multiple centers. It includes APOE4/4 individuals in the early symptomatic stages of AD, which incorporates MCI and mild AD dementia. Rigorous screening ensures that enrolled patients are between 50 and 80 years old, have a Mini-Mental State Examination score of 22 or higher, and present stable medical conditions without exclusionary MRI findings. The study successfully randomized 325 subjects, who were either given a placebo or an active dose of 265 mg ALZ-801 orally twice a day.

The trial emphasizes diversity, equity, and inclusiveness by actively recruiting underrepresented populations in the United States. Importantly, it permits participants with up to two siderosis lesions on MRI and any number of microbleeds, which are markers of cerebral amyloid angiopathy (CAA) common in APOE4/4 individuals. This is significant as previous trials of anti-amyloid antibodies often exclude individuals with more than four microbleeds.

ARIs, or amyloid-related imaging abnormalities, are concerning neurovascular injuries noted in patients using FDA-approved anti-amyloid antibodies. APOE4/4 homozygous AD patients face the highest risk of experiencing these symptomatic and serious ARIs. Consequently, the occurrence of ARIs is a crucial focus of the APOLLOE4 study.

Susan Abushakra, MD, Chief Medical Officer at Alzheon, highlighted the importance of this Phase 3 trial following promising results from a Phase 2 single-arm study. This earlier study showed significant biomarker effects without increased ARI risk in APOE4 carriers over two years. She stressed the urgent need for an effective and safe treatment for APOE4/4 homozygous AD patients, one that also avoids the complex clinical management associated with ARIs. An effective oral treatment with a straightforward regimen would significantly benefit these patients and their caregivers.

In summary, ALZ-801/valiltramiprosate holds promise as a first-in-class oral treatment for Alzheimer’s, targeting the formation of neurotoxic beta-amyloid oligomers. With its favorable safety profile and potential for robust clinical efficacy, ALZ-801 could become a groundbreaking therapy for Alzheimer’s patients, particularly those with the APOE4/4 genotype.