Clinical Trial: Phase 3 Trial of Resmetirom Versus Placebo in Metabolic Dysfunction‐Associated Steatohepatitis—Reanalysis of Fibrosis Stage 2–3 Subset

Background Resmetirom is an oral thyroid hormone receptor beta agonist clinically used to treat metabolic dysfunction‐associated steatohepatitis (MASH) among adults with stage F2 or F3 fibrosis. Aims Because the pivotal, 52‐week, randomized, controlled, phase 3 MAESTRO‐NASH trial (once‐daily oral resmetirom 80 or 100 mg or placebo) included patients with F1, F2, or F3 fibrosis, we conducted a post hoc analysis aimed at assessing treatment response in the subset of patients with stages F2 and F3 fibrosis, consistent with the approved label population. Methods Co‐primary end points were MASH resolution (hepatocellular ballooning score 0, lobular inflammation score ≤ 1, and ≥ 2‐point nonalcoholic fatty liver disease activity score [NAS] reduction from baseline) with no fibrosis worsening, and ≥ 1‐stage fibrosis improvement with no NAS worsening at Week 52. Results Among 917 patients with F2 or F3 fibrosis, metabolic risk factor prevalence was high (hypertension, 78.0%; dyslipidemia, 71.1%; type 2 diabetes, 67.0%). MASH resolution was achieved by 25.7% in the 80‐mg group, 29.9% in the 100‐mg group, and 9.5% in the placebo group ( p < 0.0001 for both comparisons with placebo). Respective percentages with fibrosis improvement were 26.5%, 28.9%, and 17.3% ( p < 0.01 for both comparisons). From baseline to Week 24, low‐density lipoprotein cholesterol decreased by 11.7% and 13.7% in the 80‐ and 100‐mg resmetirom groups, respectively, and increased by 2.3% with placebo ( p < 0.0001 for both comparisons). No new safety signals emerged. Conclusion Results among patients with F2 and F3 fibrosis were consistent with the primary MAESTRO‐NASH analysis population, demonstrating efficacy and safety of resmetirom after 52 weeks.