Alzheon Investigates Subgroup Data Following Phase 3 Trial of ALZ-801 in Alzheimer’s Disease

Phase 3 Trial Results:
Alzheon’s pivotal Phase 3 trial of ALZ-801 (valiltramiprosate), targeting individuals with the APOE4/4 genotype in early Alzheimer’s disease, did not meet its primary endpoint of significantly slowing cognitive decline. Secondary endpoints also showed no statistically significant improvement in the broader study population2 3 5 8.

Subgroup Focus:
Though the overall trial failed, a subgroup analysis revealed potential cognitive and functional benefits in participants with mild cognitive impairment (MCI), suggesting the drug might be more effective in this early symptomatic stage of the disease2 3 5.

Mechanism of ALZ-801:
ALZ-801 is a prodrug of tramiprosate designed to inhibit the formation of neurotoxic soluble amyloid oligomers, acting upstream of other amyloid-targeting treatments. It offers a potential oral alternative to costly and invasive anti-amyloid antibodies like Leqembi and Kisunla, which also pose a risk of amyloid-related imaging abnormalities (ARIA)1 4 7.

Safety Profile:
The trial indicated that ALZ-801 is safe, with no increased risk of vasogenic edema or microhemorrhages (ARIA side effects common in other amyloid-targeting therapies), making it a potentially safer option for APOE4 homozygotes5 7.

Regulatory and Future Plans:
Alzheon is assessing its next steps, including whether to pursue regulatory approval or conduct further subgroup-specific clinical trials. The company is also conducting an open-label extension study and analyzing biomarker data to support the drug’s disease-modifying potential2 5 7.

Clinical and Biomarker Results:
Despite disappointing topline results, ALZ-801 showed promising effects in slowing hippocampal shrinkage and lowering plasma biomarkers such as p-tau181, which correlate with Alzheimer’s pathology and cognitive decline. Such biomarker effects support its potential as a precision-targeted therapy for APOE4 carriers1 4 7.

Unmet Need:
ALZ-801 specifically targets the high-risk APOE4/4 population, which represents a significant unmet medical need due to limited effective, safe, and affordable treatments for this vulnerable group3 4.