Two randomized, double-blind, placebo-controlled phase III trials have evaluated the safety and anti-fibrotic efficacy of the selective ASK1 inhibitor, selonsertib, in patients with nonalcoholic steatohepatitis (NASH) with bridging fibrosis (STELLAR-3 trial) or compensated cirrhosis (STELLAR-4 trial). Patients were randomly assigned to groups receiving 6 mg or 18 mg of selonsertib or placebo daily for 48 weeks, with liver biopsies performed at the start and end of the trials and noninvasive fibrosis tests also evaluated. Although selonsertib had dose-dependent effects indicating pharmacodynamic activity, and statistically non-significant improvements were seen in noninvasive tests, both trials failed to reach the primary efficacy endpoint of fibrosis improvement without worsening of NASH at week 48. Adverse events were similar between groups.