Texas Liver Institute’s Dr. Eric Lawitz and colleagues publish clinical trial results on 2 exciting drugs in development for metabolic dysfunction-associated steatohepatitis (MASH) in the prestigious New England Journal of Medicine.
Metabolic dysfunction-associated steatotic liver disease (MASLD) includes a spectrum of histological findings ranging from hepatic steatosis (fat in the liver) to metabolic-associated steatohepatitis (MASH) (fat in the liver with inflammation). In addition to being a highly common condition affecting close to 70 million Americans, several lines of evidence suggest that MASLD, and MASH, is associated with significant liver-related morbidity and mortality. Resmetirom was recently approved by the FDA as the first approved treatment for MASH; however, there are many other promising agents in development for MASH.
Tirzepatide is a dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors and was recently FDA approved for Type 2 diabetes. The drug is a once-a-week injection and helps people lose weight by managing blood glucose levels and reducing food intake. The SYNERGY-NASH trial was just published by Dr. Lawitz and colleagues and demonstrated that patients with Type 2 diabetes who were treated with tirzepatide experienced a reduction in liver fat and improvement in biomarkers of MASH and fibrosis (New Engl J Med, June 8, 2024; DOI: 10.1056/NEJMoa2401943). Phase 3 trials will be necessary to further characterize the efficacy and safety.
Survodutide (BI456906) is a dual agonist of glucagon receptor and GLP-1 receptor. Dr. Lawitz and colleagues recently published the results of the Phase 2 trial (New Engl J Med, June 8, 2024; DOI: 10.1056/NEJMoa2401755) which demonstrated that survodutide was superior to placebo with response to improvement in MASH without worsening of fibrosis. Targeting two different pathways may lead a larger number of patients with MASH resolution and fibrosis improvement. In addition, Dr. Lawitz and colleagues published the results from a Phase 1 trial studying survodutide in patients with cirrhosis (Journal of Hepatology, June 8, 2024; DOI: 10.1016/j.jhep.2024.06.003). Phase 3 trials will be the next step to confirm the recently published findings.
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