Two Studies Detail Biomarker, Brain Preservation, and Clinical Benefits After 2-Year ALZ-801 Trial in APOE4 Early Alzheimer's

Alzheon, Inc., a biopharmaceutical firm focused on developing treatments for Alzheimer's disease (AD), recently announced significant findings from its Phase 2 biomarker trial of ALZ-801/valiltramiprosate. The study demonstrated that this investigational oral agent led to a notable and clinically relevant reduction in plasma biomarkers of neurodegeneration, as well as preservation of brain volume and cognitive improvements in patients with early AD who are carriers of the APOE4 gene.

The research, published in the journal "Drugs," highlighted two key papers. The first paper focused on the effects of ALZ-801 on plasma biomarkers, hippocampal volume, and cognition over a two-year period. The second paper provided a quantitative systems pharmacology (QSP) analysis of cerebrospinal fluid (CSF), plasma β-amyloid biomarkers, and cognition, reinforcing the therapeutic potential of ALZ-801 in modifying the disease.

Martin Tolar, MD, PhD, Founder, President, and CEO of Alzheon, emphasized the significance of these findings, stating that they support the "single toxin theory" of brain neurodegeneration. This theory posits that the aggregation of misfolded native proteins triggers the cascade leading to Alzheimer's and other neurodegenerative diseases. Tolar noted that ALZ-801, a next-generation anti-oligomer agent, has demonstrated efficacy and safety, with no increased risk of vasogenic edema. The ongoing APOLLOE4 Phase 3 trial, which is expected to report in late 2024, aims to further validate these findings.

ALZ-801 works by blocking the formation of neurotoxic soluble beta amyloid (Aβ) oligomers, which are believed to contribute to cognitive decline in Alzheimer's patients. The Phase 2 trial, which included 84 early AD patients aged 50 to 80, evaluated the drug’s impact on plasma AD biomarkers, hippocampal volume, and various cognitive tests over 104 weeks. The trial targeted patients with one or two copies of the ε4 allele of the apolipoprotein E gene (APOE3/4 and APOE4/4), a group that represents approximately 65% of Alzheimer's patients.

John Hey, PhD, Chief Scientific Officer of Alzheon, and the lead author of the publications, highlighted the trial’s positive outcomes. Participants experienced significant reductions in core AD biomarkers and brain atrophy, accompanied by cognitive stabilization over the two-year treatment period. The QSP analysis suggested that ALZ-801 effectively engages its target and holds potential for disease modification.

The study's primary efficacy endpoint—reduction in plasma p-tau181 over two years—was achieved, showing a 31% reduction from baseline to 104 weeks. Additionally, hippocampal volume atrophy was significantly reduced by 25% compared to an external control. Cognitive improvements were observed as early as 26 weeks and remained stable thereafter, correlating significantly with decreased hippocampal atrophy. The most common side effects were mild, including nausea and urinary tract infections, with no reports of serious adverse events related to the drug.

Susan Abushakra, MD, Chief Medical Officer at Alzheon, emphasized the need for well-tolerated treatments for APOE4 carriers, who are at increased risk of vascular complications. She noted that the trial data supports ALZ-801's potential as a transformative oral treatment for Alzheimer's, offering a simpler and safer alternative to existing therapies.

In summary, Alzheon's Phase 2 trial results for ALZ-801 suggest promising avenues for treating early Alzheimer's disease, particularly for patients carrying the APOE4 gene. The ongoing APOLLOE4 Phase 3 trial aims to further validate these findings, potentially leading to the first oral disease-modifying therapy for Alzheimer's disease.