Resmetirom Superior to Placebo for NASH Resolution and Liver Fibrosis Reduction

In adults with nonalcoholic steatohepatitis (NASH), resmetirom was superior to placebo for the outcomes of NASH resolution and improvement in liver fibrosis by at least one stage, according to a study published in The New England Journal of Medicine.

The phase 3 trial randomized 966 adults with NASH and a fibrosis stage of F1B, F2, or F3 (stages range from F0 [no fibrosis] to F4 [cirrhosis]) 1:1:1 to once-daily oral resmetirom at a dose of 80 mg or 100 mg or placebo. The trial’s primary endpoints were NASH resolution at week 52, including a reduction in the nonalcoholic fatty liver disease [NAFLD] activity score by 2 or more points, with no worsening of fibrosis, and a reduction in fibrosis by at least one stage with no worsening of the NAFLD activity score at week 52.

Some 25.9% of the patients in the 80-mg resmetirom group and 29.9% in the 100-mg resmetirom group achieved NASH resolution with no fibrosis worsening, according to the study, compared with 9.7% of the placebo group.

Meanwhile, 24.2% of the patients in the 80-mg resmetirom group and 25.9% of those in the 100-mg resmetirom group achieved fibrosis reduction by at least one stage with no worsening of NAFLD activity score. Just 14.2% patients in the placebo group achieved the outcome.

In other results, low-density lipoprotein cholesterol levels from baseline to week 24 decreased 13.6% with 80-mg resmetirom and 16.3% with 100-mg resmetirom. With placebo, levels increased 0.1%.

Patients who received resmetirom experienced diarrhea and nausea more often than those who received placebo, the trial found. Rates of serious adverse events, however, were similar across treatment groups: 10.9% with 80-mg resmetirom, 12.7% with 100-mg resmetirom, and 11.5% with placebo.

Reference

Harrison SA, Bedossa P, Guy CD, et al. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N Engl J Med. 2024;390(6):497-509. doi:10.1056/NEJMoa2309000