Our Approach

Clinical research focusing on underlying causes of NASH

NASH is an increasingly common serious disease of the liver with no approved treatments. Associated with metabolic disorders like diabetes and obesity, it affects more than 15 million Americans. MGL-3196 may be the first NASH therapy in development with the potential to address the root causes of the underlying disease process in NASH.

Potential to improve treatment of dyslipidemias

Patients with dyslipidemia, including potentially patients with earlier stages of fatty liver disease who, like the later stage NASH patients, are at high risk of cardiovascular disease.

Thyroid hormone regulation of lipid metabolism affects a wide range of interrelated health parameters, from levels of cholesterol and triglycerides in the blood to the pathological buildup of fat in the liver. Selective thyroid hormone receptor beta (THR)-β activation in the liver is an appealing target for therapeutics intended to address dysregulation of lipid metabolism.

Madrigal has advanced its lead candidate, 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) and heterozygous familial hypercholesterolemia (HeFH).

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 plans to initiate a Phase 3 clinical program in NASH, and a second Phase 3 clinical program in a broader segment of patients with dyslipidemia.