The New England Journal of MedicineA Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis

Injmplications for NASH Treatment: A Step Forward

A recent Phase 3, randomized, controlled trial has demonstrated the potential of resmetirom, an oral, liver-directed, thyroid hormone receptor beta–selective agonist, in treating patients with nonalcoholic steatohepatitis (NASH) accompanied by liver fibrosis. This study offers new insights into the efficacy of resmetirom in addressing a condition currently lacking approved treatments.

Study Design

• The study included adults with biopsy-confirmed NASH and a fibrosis stage of F1B, F2, or F3.
• Participants were randomly assigned in a 1:1:1 ratio to receive once-daily Resmetirom at a dose of 80 mg or 100 mg, or a placebo.
• The primary endpoints were NASH resolution without worsening of fibrosis, and fibrosis improvement by at least one stage without worsening of the NAFLD activity score at week 52.

Key Findings

• Out of 966 patients, NASH resolution without worsening of fibrosis was achieved in 25.9% and 29.9% of patients in the 80 mg and 100 mg Resmetirom groups, respectively, compared to 9.7% in the placebo group (P<0.001).
• Fibrosis improvement by at least one stage without worsening of the NAFLD activity score was seen in 24.2% and 25.9% of patients in the 80 mg and 100 mg Resmetirom groups, respectively, compared to 14.2% in the placebo group (P<0.001).
• Reduction in low-density lipoprotein cholesterol levels from baseline to week 24 was significantly greater in both Resmetirom groups compared to the placebo group.
• Diarrhea and nausea were more common in resmetirom-treated patients, but the incidence of serious adverse events was similar across all groups.

HCN Medical Memo
The Phase 3 trial findings conclusively demonstrate that both the 80-mg and 100-mg doses of resmetirom significantly outperform placebo in achieving NASH resolution and facilitating at least one stage of liver fibrosis improvement. This advancement is particularly noteworthy as it provides a promising therapeutic option for a condition that has historically lacked effective treatments. Interestingly, despite NASH being a liver-specific condition, the study has garnered considerable attention from oncologists. This engagement highlights the interdisciplinary interest in novel treatments that have broader implications, including the potential for reducing the risk of liver cancer. Thus, the results of this trial not only mark a significant step forward in the treatment of NASH but also underscore the importance of cross-specialty collaboration in addressing complex diseases.

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