A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis | New England Journal of Medicine (nejm.org)
🎯 Aim: The trial evaluated resmetirom, an oral liver-directed thyroid hormone receptor beta–selective agonist, for treating nonalcoholic steatohepatitis (NASH) with liver fibrosis.
🧪 Methodology: A phase 3 trial with 966 adults having biopsy-confirmed NASH and fibrosis. They were randomized to receive resmetirom (80 mg or 100 mg) or placebo.
🔬 Primary Endpoints: NASH resolution without fibrosis worsening and fibrosis improvement without NAFLD (nonalcoholic fatty liver disease) activity score worsening at week 52.
✅ Results: Significant NASH resolution in the resmetirom groups (25.9% at 80 mg, 29.9% at 100 mg) vs. placebo (9.7%).
📈 Fibrosis Improvement: Significant improvement in the resmetirom groups (24.2% at 80 mg, 25.9% at 100 mg) vs. placebo (14.2%).
🩸 LDL Cholesterol: Resmetirom groups saw a notable decrease in LDL cholesterol levels at week 24 (80 mg: -13.6%, 100 mg: -16.3%) compared to placebo (0.1%).
🟢 Safety: Diarrhea and nausea were more frequent with resmetirom than with placebo. Serious adverse events were similar across all groups.
🔄 Consistency: The treatment effects were consistent across various patient subgroups.
💊 Dosing: Both 80 mg and 100 mg doses of resmetirom were effective. More discontinuations were observed with the 100 mg dose.
🧐 Conclusion: Resmetirom showed superiority over placebo for NASH resolution and fibrosis improvement, with a manageable safety profile.
The article details a rigorous trial and provides evidence supporting resmetirom as a potential treatment for NASH with liver fibrosis. The reported data aligns with FDA end points for clinical benefit in NASH and was approved this month, although long-term clinical outcomes data is still needed.
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