Home Medizin NEJM-Studie unterstreicht die Wirksamkeit von Resmetirom bei NASH

NEJM-Studie unterstreicht die Wirksamkeit von Resmetirom bei NASH

von NFI Redaktion

The oral beta-selective agonist of the thyroid hormone receptor, Resmetirom (Madrigal Pharmaceuticals), in both 80 mg and 100 mg doses, was found to be superior to placebo in resolving non-alcoholic steatohepatitis (NASH) and improving liver fibrosis, according to the results of the ongoing Phase 3 MAESTRO-NASH study published in the New England Journal of Medicine on February 7th.

Although certain results of this study were originally presented at the European Association for the Study of the Liver Congress in 2023, the publication of the full expert-reviewed paper represents a potentially significant milestone in the treatment of NASH, a disease for which there is currently no approved pharmacological treatment.

„Data from the first 1,050 patients in the MAESTRO-NASH study, along with data from completed Resmetirom studies, support the potential of Resmetirom to provide benefits for patients with NASH and liver fibrosis,“ wrote the authors led by principal investigator Stephen Harrison, MD, Chairman of Pinnacle Clinical Research and Summit Clinical Research in San Antonio, Texas.

The study used the earlier nomenclature of NASH and non-alcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to „metabolic dysfunction-associated steatohepatitis“ (MASH) and „metabolic dysfunction-associated steatotic liver disease“ (MASLD).

A closer look at MAESTRO-NASH

The researchers recruited 996 participants who were randomly assigned to receive either placebo or Resmetirom at a dose of 80 mg or 100 mg. The patients were observed for 52 weeks and then assessed for the two primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) without worsening of fibrosis and improvement (reduction) of fibrosis by at least one stage without worsening of the NAFLD activity score.

They observed a significant improvement in patients receiving Resmetirom at both doses and for both primary endpoints. In the 80 mg and 100 mg groups, NASH resolution without worsening of fibrosis was achieved in 25.9% and 29.9% of patients, respectively, compared to 9.7% under placebo. A reduction of fibrosis by at least one stage without worsening of the NAFLD activity score was achieved in 24.2% and 25.9% of patients in the escalating dose groups, compared to 14.2% under placebo (P < .001 for both doses compared to placebo).

The effects of Resmetirom were consistent across all major subgroups, regardless of baseline fibrosis stage, NAFLD activity score at study entry, or Type 2 diabetes status, age, and gender.

„Several non-invasive tests for NASH, steatosis, and fibrosis (including blood biomarkers and imaging) showed a similar direction of effect in favor of Resmetirom treatment, supporting the results for the primary endpoints,“ wrote Harrison and colleagues.

The majority of NASH patients also suffer from diabetes. Therefore, it is known that NASH patients have a high cardiovascular risk and high mortality. However, MAESTRO-NASH researchers reported that patients receiving Resmetirom showed a reduction in levels of a broad range of atherogenic lipids and lipoproteins, including low-density lipoprotein cholesterol (LDL), non-high-density lipoprotein cholesterol, and triglycerides, apolipoprotein B, and lipoprotein(a). These results were consistent with previous studies on Resmetirom.

From baseline to week 24, LDL cholesterol levels decreased by -13.6% in the 80 mg group and by -16.3% in the 100 mg Resmetirom group, compared to 0.1% in the placebo group (P < .001).

More patients in the 100 mg group discontinued the study due to adverse events compared to the 80 mg or placebo groups (6.8% vs. 1.8% and 2.2%). Diarrhea and nausea were more common in the Resmetirom group than in the placebo group. Serious adverse events occurred with similar frequency in the 100 mg, 80 mg, and placebo groups (12.7%, 10.9%, and 11.5%).

Although the MAESTRO-NASH study is currently lacking in clinical outcomes, the researchers will collect data on liver-related outcomes over the planned 54-month duration, including progression to liver cirrhosis. Similarly, long-term safety data will be available upon completion of the study.

Disclosure forms provided by the authors are available along with the full text of the NEJM paper on NEJM.org.

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