A randomized, double-blind, placebo-controlled phase IIa trial of efruxifermin for patients with compensated NASH cirrhosis

作者：Stephen A. Harrison, Peter Ruane, B. Freilich, Guy Neff, Rashmee Patil, Cynthia Behling, Chen Hu, Reshma Shringarpure, Brittany de Temple, Erica Fong, Erik J. Tillman, Tim Rolph, Andrew Cheng, Kitty Yale · 发表于：JHEP Reports · 年份：2022 · DOI：10.1016/j.jhepr.2022.100563 · 被引用次数：103 · 研究领域：Liver Disease Diagnosis and Treatment、Drug-Induced Hepatotoxicity and Protection、Liver physiology and pathology

Background & Aims Efruxifermin has shown clinical efficacy in patients with non-alcoholic steatohepatitis (NASH) and F1–F3 fibrosis. The primary objective of the BALANCED Cohort C was to assess the safety and tolerability of efruxifermin in patients with compensated NASH cirrhosis. Methods Patients with NASH and stage 4 fibrosis (n = 30) were randomized 2:1 to receive efruxifermin 50 mg (n = 20) or placebo (n = 10) once-weekly for 16 weeks. The primary endpoint was safety and tolerability of efruxifermin. Secondary and exploratory endpoints included evaluation of non-invasive markers of liver injury and fibrosis, glucose and lipid metabolism, and changes in histology in a subset of patients who consented to end-of-study liver biopsy. Results Efruxifermin was safe and well-tolerated; most adverse events (AEs) were grade 1 (n = 7, 23.3%) or grade 2 (n = 19, 63.3%). The most frequent AEs were gastrointestinal, including transient, mild to moderate diarrhea, and/or nausea. Significant improvements were noted in key markers of liver injury (alanine aminotransferase) and glucose and lipid metabolism. Sixteen-week treatment with efruxifermin was associated with significant reductions in non-invasive markers of fibrosis including Pro-C3 (least squares mean change from baseline [LSMCFB] −9 μg/L efruxifermin vs. −3.4 μg/L placebo; p = 0.0130) and ELF score (−0.4 efruxifermin vs. +0.4 placebo; p = 0.0036), with a trend towards reduced liver stiffness (LSMCFB −5.7 kPa efruxifermin vs. −1...