Resmetirom: The First Food and Drug Administration-Approved Medication for Nonalcoholic Steatohepatitis (NASH)

Abstract

Objective: To review the literature leading to the Food and Drug Administration (FDA) approval of the first medication, resmetirom, for the treatment of nonalcoholic steatohepatitis (NASH), including the pharmacology, pharmacokinetics, clinical studies, dosing, and adverse effects. Relevant data will be used to discuss how resmetirom impacts clinical practice.

Data sources: A literature search was conducted using MEDLINE from database inception to May 12, 2024. Keywords included non-alcoholic steatohepatitis, nonalcoholic fatty liver disease, and resmetirom. Study selection, data extraction and all English-language studies involving the use of resmetirom for nonalcoholic fatty liver disease (NAFLD)/NASH were included.

Data synthesis: Resmetirom, a thyroid hormone receptor agonist, is administered at daily doses of either 80 mg or 100 mg. The drug was shown to provide NASH resolution as assessed by the NAFLD activity score, 80 mg-24.2%, 100 mg-25.9% compared to 14.2% with the placebo group (P < 0.001). Resmetirom, improved liver fibrosis, 80 mg-25.9%, 100 mg-29.9% compared to 9.7% with the placebo group (P < 0.001). Resmetirom's ability to improve fibrosis in patients with F2-F3 fibrosis offers valuable benefit for patients at risk of progressing to cirrhosis.

Relevance to patient care and clinical practice: Resmetirom expands the medication options available to treat patients with NASH which can be given alongside other medications to optimize metabolic factors such as glucagon-like peptide-1 and hydroxymethylglutaryl-coenzyme A reductase inhibitors. Resmetirom was well tolerated in studies.

Conclusion: Resmetirom serves as an attractive option in patients diagnosed with NASH with evidence of advanced fibrosis (F2-F3) in combination with exercise, diet, and other multimodal therapies targeting metabolic risk factors.

Keywords: drug development and approval; metabolic dysfunction-associated steatohepatitis; metabolic dysfunction-associated steatotic liver disease; metabolic syndrome; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; resmetirom; thyromimetic drugs.