Photo Credit: Mohammed Haneefa Nizamudeen

The following is a summary of “A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis,” published in the February 2024 issue of Endocrinology by Harrison et al.

Researchers conducted a prospective study to evaluate the efficacy of resmetirom, an oral, liver-targeted, selective thyroid hormone receptor beta agonist, in the treatment of Nonalcoholic steatohepatitis (NASH) with liver fibrosis, a progressive liver disease lacking approved therapies.

They are conducting an ongoing phase 3 trial involving adults diagnosed with biopsy-confirmed NASH and a fibrosis stage ranging from F1B, F2, or F3 (stages from F0 [no fibrosis] to F4 [cirrhosis]). Participants in the trial were assigned in a 1:1:1 ratio to receive either once-daily doses of resmetirom at 80 mg or 100 mg or placebo. The trial’s two primary endpoints at week 52 include resolution of NASH (comprising a decrease in the nonalcoholic fatty liver disease [NAFLD] activity score by ≥2 points; scores ranging from 0 to 8, where higher scores denote more severe disease), without worsening fibrosis, and improvement (reduction) in fibrosis by at least one stage without worsening of the NAFLD activity score.

The results demonstrated that among the 966 patients in the primary analysis cohort (322 in the 80-mg resmetirom group, 323 in the 100-mg resmetirom group, and 321 in the placebo group), NASH resolution without exacerbating fibrosis was achieved by 25.9% of individuals in the 80-mg resmetirom group and 29.9% in the 100-mg resmetirom group, as opposed to 9.7% in the placebo group (P<0.001 for both comparisons with placebo). Improvement in fibrosis by at least one stage without worsening NAFLD activity score was achieved by 24.2% in the 80-mg resmetirom group and 25.9% in the 100-mg resmetirom group, versus 14.2% in the placebo group (P<0.001 for both comparisons with placebo). The decrease in low-density lipoprotein cholesterol levels from baseline to week 24 was -13.6% in the 80-mg resmetirom group and -16.3% in the 100-mg resmetirom group, compared to 0.1% in the placebo group (P<0.001 for both comparisons with placebo). Diarrhea and nausea were more familiar with resmetirom compared to placebo. The occurrence of severe adverse events was comparable among the trial groups, with rates of 10.9% in the 80-mg resmetirom group, 12.7% in the 100-mg resmetirom group, and 11.5% in the placebo group.

Investigators concluded that 80 mg and 100mg of resmetirom significantly improved NASH resolution and liver fibrosis in a clinical trial compared to placebo.

Source: nejm.org/doi/full/10.1056/NEJMoa2309000