AASLD Liver Meeting 2021 | Nov. 2021
Authors: Szilvia Kiriakov1, Matthew Russell2, Andrew Downey2, Noriaki Tatsuta2, Margaret J Koziel2, Michael Hamill3, and Karim Azer2
Nonalcoholic fatty liver disease (NAFLD) is prevalent in >25% of the global population and in 50% to 90% of obese adults. Once nonalcoholic steatohepatitis (NASH) occurs, there may be progression to cirrhosis. Patients with NASH may benefit from approaches that concurrently address multiple metabolic and fibroinflammatory pathways; however, at present, there are no approved therapies. In early NAFLD clinical studies, AXA1125, an investigational oral endogenous metabolic modulator (EMM) composition of 5 selectively combined amino acids (AAs; leucine, isoleucine, valine, arginine, glutamine) and N-acetylcysteine, simultaneously supported multiple metabolic biologies and pathways of NAFLD, 6 improving insulin sensitivity, inflammation, fibrosis, and magnetic resonance imaging-proton density fat fraction (MRI-PDFF) (AXA1125-002, 7 -0038 ). Changes in proton density fat fraction (PDFF) have been linked to histologic improvement in NASH with fibrosis in other therapeutic trials. In vitro studies in primary human hepatocytes indicated that AXA1125 impacted multiple metabolic pathways such as AA metabolism (involving branched-chain amino acids [BCAAs]), the urea cycle, and peroxisome proliferator-activated receptor pathway which regulates metabolism of fatty acids, among others.