LIVRQNac (AXA1125) Enhances Insulin Sensitivity in Primary Human Hepatocytes and in Subjects With NAFLD and T2D

Introduction

Nonalcoholic fatty liver disease (NAFLD) is a multifactorial condition that is mediated by dysregulated metabolic and fibroinflammatory pathways. Insulin resistance, commonly manifested as type 2 diabetes (T2D), is an important driver of NAFLD and targeting these metabolic pathways is a potential therapeutic strategy.  Endogenous metabolic modulators (EMMs), a broad set of physiologically intrinsic molecules such as amino acids, fatty acids, and other lipids, can be selectively combined to form compositions that target multiple metabolic pathways key to multifactorial liver diseases such as NAFLD.  AXA1125 is a novel, orally administered investigational EMM composition comprising 5 amino acids and a derivative: leucine, isoleucine, valine, arginine, glutamine, and N-acetyl cysteine; LIVRQNac has the same constituent components combined at different relative ratios for use in vitro at supraphysiologic concentrations.  A clinical study (AXA1125-002) previously assessed the safety, tolerability, and biological activity of AXA1125 in subjects with NAFLD and T2D.  Positive directional changes in biomarkers related to liver fat, insulin sensitivity, inflammation, and fibrosis were observed; these results have been supported by findings in primary human cell-based systems exposed to AXA1125.