Results of the MAESTRO-NASH clinical trial: hope for the treatment of MASH (NASH) with liver fibrosis?

Metabolic steatohepatitis or MASH (formerly NASH) is a progressive liver disease for which there is no approved treatment. Yet “fatty liver disease” affects 25% of the world’s population, and it is estimated that 1 in 5 patients with MAFLD (hepatic steatosis associated with a metabolic disorder) will develop MASH.

Resmetirom is an orally administered, liver-targeted, beta-selective agonist of the thyroid hormone receptor. This treatment, currently under development, is used in the treatment of MASH accompanied by liver fibrosis (affecting around 1.5% of the general population).

Prof. Vlad Ratziu (Hepatologist, AP-HP, Sorbonne University, Inserm, IHU ICAN) has participated as co-lead investigator in a new Phase III clinical trial on the efficacy of resmetirom in the treatment of MASH.

The results were reported on February 8, 2024 in the prestigious scientific journal The New England Journal of Medicine: “A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis”.

On March 14, 2024, the FDA (Food and Drug Administration) approved resmetirom as the 1st drug to treat metabolic steatohepatitis (MASH)!

The methodology: a phase 3 clinical trial in patients with MASH (NASH) and fibrosis

  • Resolution of MASH (NASH), without worsening fibrosis, was achieved in:
    • 25.9% of patients in the 80 mg resmetirom group,
    • 29.9% of those in the 100 mg resmetirom group,
    • compared with 9.7% in the placebo group.
  • Improvement of fibrosis by at least one stage, without worsening of the NAFLD activity score, was achieved in:
    • 24.2% of patients in the 80 mg resmetirom group,
    • 25.9% of those in the 100 mg resmetirom group,
    • compared with 14.2% of those in the placebo group.
  • The change in low-density lipoprotein cholesterol from baseline to week 24 was :
    • -13.6% in the group receiving 80 mg resmetirom
    • -16.3% in the 100 mg resmetirom group,
    • compared with 0.1% in the placebo group.
  • The incidence of serious adverse events was similar in all trial groups:
    • 10.9% in the resmetirom 80 mg group,
    • 12.7% in the resmetirom 100 mg group,
    • 11.5% in the placebo group.
  • Diarrhea and nausea were more frequent with resmetirom than with placebo.

The 80 mg and 100 mg doses of resmetirom were superior to placebo in resolving NASH and improving liver fibrosis by at least one stage.

A breakthrough in the drug treatment of MASH (NASH)

This trial opens up new prospects for the creation of a treatment to combat non-alcoholic steatohepatitis, or MASH, the prevalence of which is increasing year after year throughout the world.

In fact, this cardiometabolic disease can lead to other serious pathologies, due to the metabolic dysfunctions observed in patients:

  • Depending on the presence of risk factors, the prevalence of NAFLD varies from 5.2% in non-diabetic subjects of normal weight, to 90% in diabetic and obese subjects.
  • Among patients with NAFLD, the prevalence of advanced fibrosis is estimated at 2.5%, corresponding to around 230,000 people in mainland France.
  • These figures are reinforced by the epidemic of obesity and type 2 diabetes in France and around the world.

IHU ICAN experts are developing cutting-edge research projects to build tomorrow’s medicine for cardiometabolic diseases.

A specialist in metabolic steatohepatitis (MASH), Prof. Vlad Ratziu has taken part in numerous therapeutic trials on this pathology, and has published over 300 articles in numerous international journals. He works at the ICAN IHU’s NASH clinic, which offers an innovative, personalized care pathway to optimize the diagnosis and management of non-alcoholic fatty liver.