Miricorilant, a Selective Glucocorticoid Receptor Modulator, Reprograms Hepatic Gene Networks in Metabolic Dysfunction–Associated Steatohepatitis
Summary
- Miricorilant selectively modulated key genes in pathways regulating hepatic steatosis, metabolism, oxidative stress, inflammation, and fibrosis
- Early response (8 h exposure) was characterized by upregulation of genes associated with lipid metabolism, detoxification, and cellular stress responses, indicating enhanced hepatic metabolic function and immediate protection against oxidative and inflammatory stress
- Sub-chronic response (5 d exposure) was characterized by sustained upregulation of lipid metabolism regulators and downregulation of gluconeogenic enzymes, supporting long-term improvements in hepatic steatosis, insulin sensitivity, and potentially fibrosis
- Collectively, these results highlight the potential of miricorilant as a liver-targeted therapy for MASH (metabolic-associated steatohepatitis) as it operates through the selective and time-dependent modulation of key pathophysiological processes
- The ongoing phase 2b MONARCH trial (NCT06108219) is currently evaluating miricorilant in patients with biopsy confirmed or presumed noncirrhotic MASH