Significance of ALZ-801’s Impact on Carriers of APOE e4 Alleles: Susan Abushakra, MD

WATCH TIME: 3 minutes

"All the outcomes we saw fit together well with our basic mechanism of action, which is the following: you’re able to inhibit the formulation of the soluble amyloid oligomers, which are the most toxic species. By that, we’re able to reduce p-tau early, significantly, and robustly. Because it’s not enough to just have any p-tau reduction, even if its significant at 10% it may not be meaningful. We have multiples of that, 41% is a large effect that starts early and is consistent over a year."

Of the several therapies being presented at the 2022 Clinical Trials on Alzheimer Disease (CTAD) conference, held November 29 to December 2, in San Francisco, California, Alzheon’s ALZ-801 may represent a unique approach, as it has shown early success of patients at high-risk for Alzheimer disease (AD). ALZ-801 or valiltramiprosate, is a prodrug of homotaurine, a modified amino acid, and has been evaluated across a few studies, including a notable phase 2 open-label biomarker study (NCT04693520) and an ongoing phase 3 study, dubbed APOLLOE4 that began in May 2021.

Led by Susan Abushakra, MD, the phase 2 study included 84 patients with early AD with either apolipoprotein (APOE) e4/4 or APOE e3/4 genotypes and a prior positive amyloid-PET or cerebrospinal fluid biomarkers fulfilling amyloid positive and tau positive criteria. The findings presented at CTAD 2022 showed significant reduction of plasma phosphorylated-tau (p-tau)181 at 13 and 26 weeks, that reached to –41% after 52 weeks of treatment. Additionally, bilateral hippocampal volume atrophy at 1 year was reduced by 25% compared with matched subjects from the Alzheimer’s Disease Neuroimaging Initiative.

APOE e4 carriers, considered the most at risk for AD, are considered a high area of research focus; however, few therapies have specifically been tested in these subsets alone. In an interview with NeurologyLive^®, Abushakra, the chief medical officer of Alzheon, provided perspective on the significance of ALZ-801’s impact on genetically at-risk individuals, and the need to treat this population as early as possible.

Click here for more coverage of CTAD 2022.

REFERENCE
1. Abushakra S, Hey J, Bennow K, et al. Significant effects of oral ALZ-801 on plasma biomarkers of Alzheimer’s disease: 12-month interim analysis of phase 2 biomarker study in APOE4 carriers with early AD. Presented at: 2022 CTAD Conference; November 29-December 2; San Francisco, CA. Abstract OC27