BACKGROUND: Fibroblast growth factor 21 (FGF21) is a metabolic regulator with demonstrated efficacy for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). FGF21 signals through 'c' isoforms of the FGF receptors (FGFR) 1-3 and the co-receptor β-klotho. AIMS: We report the safety and efficacy of MK-3655, a monoclonal antibody that binds β-klotho and selectively activates the FGFR1c/β-klotho co-receptor complex, in patients with pre-cirrhotic MASH. METHODS: Phase 2b, randomised, multicenter, double-blind, placebo-controlled, parallel-group study in patients with pre-cirrhotic MASH (NAS ≥ 4 and MASH CRN fibrosis score Stage 2 or 3). Participants were randomised 1:1:1:1 to receive MK-3655 50 mg, 100 mg, 300 mg, or matching placebo subcutaneously every 4 weeks. The primary endpoint was MASH resolution without worsening of fibrosis by histology at Week 52. An interim analysis (IA) of liver fat content (LFC) was planned once ≥ 25 participants per treatment group completed an MRI-PDFF assessment at Week 24. RESULTS: Among 183 participants, mean BMI was 33.4 kg/m CONCLUSIONS: In patients with pre-cirrhotic MASH, treatment with MK-3655 resulted in a modest reduction in LFC at 24 weeks. CLINICAL TRIAL NUMBER: EudraCT: 2019-003048-63
NCT: 04583423.