{Reference Type}: Journal Article
{Title}: Review of valiltramiprosate (ALZ-801) for the treatment of Alzheimer's disease: a novel small molecule with disease modifying potential.
{Author}: Lee D;Antonsdottir IM;Clark ED;Porsteinsson AP;
{Journal}: Expert Opin Pharmacother
{Volume}: 25
{Issue}: 7
{Year}: 2024 May 30
{Factor}: 4.103
{DOI}: 10.1080/14656566.2024.2360069
{Abstract}: <B>UNASSIGNED: </B>Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive deterioration, functional impairments, and neuropsychiatric symptoms. Valiltramiprosate is a tramiprosate prodrug being investigated as a novel treatment for AD.<BR><B>UNASSIGNED: </B>The online databases PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched using the terms 'ALZ-801' or 'valiltramiprosate.' Alzheon press releases were reviewed for emerging clinical information. Valiltramiprosate is an oral, well-tolerated synthetic valine-conjugate prodrug of tramiprosate. Valiltramiprosate's active metabolite include tramiprosate and 3-sulfopropanoic acid. Proposed mechanism of action is multiligand binding to Aβ42 which stabilizes amyloid monomers to prevent peptide aggregation and oligomerization. Pharmacokinetic studies show 52% oral bioavailability, rapid absorption, approximately 40% brain-drug exposure, and near complete renal clearance. Compared to tramiprosate, valiltramiprosate extends plasma tramiprosate half-life and improves interindividual pharmacokinetic variability. Interim analyses from valiltramiprosate's phase II biomarker trial show: (1) significant reductions in plasma p-tau181 and related AD fluid biomarkers; (2) brain structure preservation and reduced hippocampal atrophy by MRI; and (3) improvements on cognitive assessments at multiple timepoints. Its phase III clinical trial in ApoE ε4 homozygotes is near completion.<BR><B>UNASSIGNED: </B>Valiltramiprosate's clinical trial data show early indications of efficacy with potential disease modifying effect in AD.