MGL-3196 is a first-in-class, orally administered, small-molecule, liver-directed, THR β-selective agonist. Preclinical, toxicology and Phase 1 clinical data suggest MGL-3196 has an attractive, differentiated profile as a potential treatment for non-alcoholic steatohepatitis (NASH) and dyslipidemias.
THR-β selectivity also enhances the safety profile of MGL-3196, compared to non-selective agents. MGL-3196 has shown no suppression of the central thyroid axis, no THR-α effects on heart rate or bone, and no elevation of liver enzymes. These characteristics make MGL-3196 among the most promising molecules in development in this therapeutic area.
The Company recently initiated a randomized, double-blind, placebo-controlled, multi-center Phase 2 study in 117 patients 18 years of age and older with biopsy-confirmed NASH. The primary endpoint of the study is the reduction of liver fat at 12 weeks, evaluated with MRI-PDFF (magnetic resonance imaging-estimated proton density fat fraction), a novel non-invasive imaging-based biomarker. This provides an early indicator of efficacy, which will be confirmed at the end of the trial (36 weeks) by conventional liver biopsy to examine histological evidence for the resolution of NASH. Recent published data show a high correlation of reduction of liver fat measured by MRI-PDFF to NASH scoring on liver biopsy.
More information about the NASH Phase 2 study [NCT02912260] is available at www.ClinicalTrials.gov.
Additionally, Madrigal initiated a Phase 2, placebo-controlled study of MGL-3196 in heterozygous familial hypercholesterolemia (HeFH). The primary endpoint in the 12-week trial will be the reduction of LDL cholesterol, with secondary endpoints including reductions of triglycerides, Lp(a), and ApoB, and evaluation of safety.
More information about the HeFH Phase 2 study [NCT03038022] is available at www.ClinicalTrials.gov.
A protocol for a Phase 2, open-label study of MGL-3196 in homozygous familial hypercholesterolemia (HoFH) is also in development. The 12-week trial will have endpoints similar to the HeFH study.