Metabolomic and Lipidomic Analysis of Patients with Presumed Metabolic Dysfunction-Associated Steatohepatitis (MASH) Treated with the Selective Glucocorticoid Receptor Modulator Miricorilant

Summary & Conclusions 

• • • The observed declines in intermediate lipid species suggest that responders (patients with ≥30% reduction from baseline in liver fat content (LFC) following miricorilant treatment), particularly those with rapid LFC clearance accompanied by efficacy-associated alanine aminotransferase (ALT) elevations (rapid responders [RR]), experienced enhanced metabolic clearance of lipids and fatty acids
      • In RRs, metabolic clearance of acylglycerols continued to improve at week 12 despite discontinuation or interruption of miricorilant after week 6
    • Rapid changes in liver metabolism, such as increased fatty acid oxidation, can cause transient hepatic stress. This stress may produce a short-term rise in ALT levels as the liver adjusts to the new metabolic conditions
      • Although this may cause transient hepatic stress, it points to improved hepatic lipid metabolism
    • Changes in bile metabolism could suggest elevated liver capacity to synthesize bile acids, enhancing lipid emulsification or clearance
    • The ongoing phase 2b MONARCH study is assessing 100 mg miricorilant twice weekly, a dose that resulted in improved LFC without ALT elevations in miricorilant’s phase 1b study, and a higher dose of 200 mg twice weekly after a 6-week lead-in of 100 mg twice weekly

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