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.