On 1 April, Alzheon, a clinical-stage biopharmaceutical company developing a broad portfolio of investigational therapies and diagnostic assays for people with Alzheimer’s disease (AD) and other neurodegenerative disorders, announced topline results from its pivotal APOLLOE4 Phase 3 trial of oral valiltramiprosate in people with early AD. Findings were presented at a symposium during the International Conference on Alzheimer’s and Parkinson’s Disease and Related Neurological Disorders (AD/PD) in Vienna, Austria. The APOLLOE4 study was designed to evaluate the efficacy, safety, biomarker and imaging effects of 265 mg twice daily oral dose of valiltramiprosate (ALZ-801) in people with early AD with two copies of the apolipoprotein ε4 allele (APOE4/4 homozygotes), who constitute approximately 15% of AD patients.
The trial enrolled 325 participants, from North America and Europe, who received either valiltramiprosate or placebo for 78 weeks. Findings showed that the APOLLOE4 trial did not meet its primary endpoint, change from baseline in Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog13). However, a prespecified analysis of the population with Mild Cognitive Impairment (MCI), which accounted for a quarter of the overall trial population, showed that treatment with valiltramiprosate was found to be significantly effective over 78 weeks. Compared with placebo, treatment with valiltramiprosate resulted in a 52% benefit on the ADAS-Cog13 scale, with differences between the treatment group and placebo group seen from 13 weeks.
In the MCI population, valiltramiprosate treatment also resulted in improvements, while not statistically significant, in the Clinical Dementia Rating – Sum of Boxes (CDR-SB) scores, mini-mental state examination (MMSE) scores, and Amsterdam – Instrumental Activities of Daily Living (A-IADL) scores. An ongoing long-term extension of the trial, APOLLOE4-LTE, evaluates valiltramiprosate in people who complete the core APOLLOE4 study for an additional 52 weeks of treatment for a total of 130 weeks. This long-term extension study is currently ongoing in the US, UK and Canada.