Increased Adiponectin following Efruxifermin Treatment Is Associated with Improvements in Dyslipidemia, Glucose Metabolism, and Liver Health in a 16-Week, Randomized, Placebo-Controlled NASH Trial

FGF21, an endocrine hormone that regulates whole-body metabolism during energy imbalance, is a promising therapeutic target. Efruxifermin (EFX), an Fc-FGF21 analog, is a balanced FGFR1c, 2c, and 3c agonist under investigation as a potential treatment for nonalcoholic steatohepatitis (NASH). In a clinical trial in biopsy-confirmed NASH, EFX significantly reduced liver fat content (LFC), ALT, and AST, and increased adiponectin.1 Activating FGFR1c in adipose tissue increases circulating adiponectin; the aim of this analysis was to evaluate correlations between changes in adiponectin and markers of dyslipidemia, glucose metabolism and liver health following EFX treatment. Patients (N=80) were randomized to placebo or 28, 50, or 70mg EFX. Larger increases in adiponectin correlated with greater improvements in lipid profiles, including decreases in triglycerides and increases in HDL-C, as well as decreases in LFC (Table). Increases in adiponectin also correlated strongly with markers of improved glucose metabolism, and greater reductions in markers of liver injury and fibrosis. These data suggest adipose tissue-mediated effects of EFX contribute substantially to restoration of liver health, healthy lipoprotein profiles, insulin sensitivity and glucose tolerance.1 Harrison 2020 Hepatol 72 1S; 6AView largeDownload slideView largeDownload slide DisclosureJ. Frias: Consultant; Self; 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc., Sanofi, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, CymaBay Therapeutics, Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi, Speaker’s Bureau; Self; Merck & Co., Inc., Sanofi. E. J. Tillman: Employee; Self; Akero Therapeutics, Inc., Stock/Shareholder; Self; Akero Therapeutics, Inc. R. Shringarpure: Employee; Self; Akero Therapeutics, Inc., Stock/Shareholder; Self; Akero Therapeutics, Inc. E. Fong: Employee; Self; Akero Therapeutics, Inc. B. De temple: Employee; Self; Akero Therapeutics, Inc. T. Rolph: Employee; Self; Akero Therapeutics, Inc., Stock/Shareholder; Self; Pfizer Inc. A. Cheng: Employee; Self; Akero Therapeutics, Inc. K. Yale: Employee; Self; Akero Therapeutics, Inc. S. A. Harrison: Consultant; Self; Axcella Health Inc.