Semaglutide for the treatment of non-alcoholic steatohepatitis: Trial design and comparison of non-invasive biomarkers.

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease. There is a clear need to develop pharmacological treatment for patients with NASH as well as biomarkers that can diagnose the disease. We describe a trial of semaglutide treatment for NASH, identify key patient characteristics and compare the relationship of patient characteristics and non-invasive biomarkers/scores. NCT02970942 is a randomised, double-blind, placebo-controlled, multi-national Phase 2 trial of daily subcutaneous semaglutide (0.1 mg, 0.2 mg, 0.4 mg) in patients with biopsy-confirmed NASH, F1-F3 fibrosis, NAFLD Activity Score ≥ 4, and body mass index (BMI) > 25 kg/m. Exploratory analyses were performed to evaluate correlations between baseline parameters and biomarkers in NASH. Mean (standard deviation [SD]) age of 320 randomised patients was 55 (11) years, mean BMI was 36 (6) kg/m, and 199 (62%) had type 2 diabetes. Of the total patients, 28% had F1 fibrosis, 23% had F2 fibrosis and 49% had F3 fibrosis. The highest area under the receiver operating characteristic curve (0.69) for accuracy in classifying fibrosis stage, F2-3 versus F1, was observed for Fib-4 and Enhanced Liver Fibrosis (ELF). No substantial correlation between BMI or other clinical or biochemical parameters and fibrosis stage was observed. In this large Phase 2 trial of semaglutide treatment for NASH, the clinical profile of enrolled patients was typical for patients with NASH. Of the investigated biomarkers/scores, ELF and Fib-4 showed the most apparent correlation in classifying fibrosis stage, but had only moderate predictive value.