Madrigal Pharmaceuticals, Inc. (Nasdaq: MDGL) is a clinical-stage biopharmaceutical company pursuing novel therapeutics that target a specific thyroid hormone receptor pathway in the liver, which is a key regulatory mechanism common to a spectrum of cardio-metabolic and fatty liver diseases with high unmet medical need. The company has advanced its lead candidate, resmetirom, also known as MGL-3196, a first-in-class, orally administered, small-molecule, liver-directed, thyroid hormone receptor (THR) β-selective agonist, through Phase 2 clinical trials in non-alcoholic steatohepatitis (NASH). Primary and key secondary endpoints were achieved, including reduction of liver fat on a sensitive non-invasive imaging test, lowering of multiple atherogenic lipids including LDL-cholesterol and triglycerides, and resolution of NASH on liver biopsy.

Based on evidence of broad activity and a favorable safety profile, Madrigal has initiated a Phase 3 clinical study in NASH patients with advanced liver fibrosis, MAESTRO-NASH, in which the primary endpoint after one year of dosing is resolution of NASH and key secondary endpoints include LDL-cholesterol lowering and reduction in liver fibrosis. Clinical benefit in reducing progression to more advanced liver disease, including cirrhosis, is a long-term goal of this trial.

A second Phase 3 clinical study, MAESTRO-NAFLD-1 (NAFLD: non-alcoholic fatty liver disease), has also been initiated. This 52-week, non-invasive study in a broader segment of NASH patients will provide additional safety information to support the NASH indication and will include key efficacy endpoints: LDL-cholesterol lowering, triglyceride lowering, reduction of liver fat as determined by magnetic resonance imaging proton density fat fraction (MRI-PDFF), as well as reduction of elevated liver enzymes and reduction in fibrosis biomarkers. This is a non-biopsy study in people with NASH, as documented using non-invasive techniques or historical liver biopsy.