3 Key Takeaways
Plain English Summary- 01Core Finding
Seventy patients with presumed MASH received oral miricorilant daily (30-150 mg) or intermittent (100-200 mg once, twice, or thrice weekly) dosing regimens for 12 or 24 weeks.
- 02Study Evidence
Tested in a observational cohort study (n=9) at the real-world cohort stage.
- 03Practical Meaning
Observational cohort findings reveal real-world links, though lifestyle or unmeasured factors cannot be fully ruled out without an RCT.
What This Means for You
Intermittent miricorilant dosing of 100 mg twice weekly achieved meaningful reductions in LFC and improved liver health markers with a favorable safety profile. This regimen is being evaluated in the phase 2b MONARCH study (NCT06108219).
The Discovery
Miricorilant, an oral nonsteroidal selective glucocorticoid receptor modulator, is being investigated as a therapy that modulates hepatic cortisol activity in patients with metabolic dysfunction-associated steatohepatitis (MASH). This phase 1b study (NCT05117489) evaluated miricorilant's efficacy (real-world effectiveness in the trial) and safety. Seventy patients with presumed MASH received oral miricorilant daily (30-150 mg) or intermittent (100-200 mg once, twice, or thrice weekly) dosing regimens for 12 or 24 weeks. Across dosing regimens, reductions in relative liver fat content (LFC) ranged from a clinically meaningful level to 76.6%. Improvements in MASH liver function markers and the enhanced liver fibrosis (ELF) score were observed across regimens. Treatment-emergent adverse events (TEAEs) leading to drug interruption/discontinuation occurred in a clinically meaningful level of patients (n=9) each; most were due to aminotransferase elevations during an excessively rapid drop in LFC (substantially at week 6) and in patients receiving daily dosing. Intermittent dosing enabled more patients to complete 12 weeks of treatment without discontinuation due to TEAEs. Intermittent dosing with miricorilant 100 mg twice weekly had the best benefit-risk profile; this cohort demonstrated a mean LFC reduction of 28.2% at week 12, with a corresponding decline in liver enzymes (ALT, -3.8 U/L; AST, -6.0 U/L). Patients in this cohort also had numerical improvement in lipid profiles, glycemic markers, and fibrosis (tissue scarring) biomarkers.
How It Works, Simply
This gastroenterology research focuses on receptor targeting · Enzyme · Blood biomarker (measurable biological signal). Researchers evaluated it using an observational cohort study (n=9) at the real-world cohort stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
Seventy patients with presumed MASH received oral miricorilant daily (30-150 mg) or intermittent (100-200 mg once, twice, or thrice weekly) dosing regimens for 12 or 24 weeks.
- 02Study Evidence
Tested in a observational cohort study (n=9) at the real-world cohort stage.
- 03Practical Meaning
Observational cohort findings reveal real-world links, though lifestyle or unmeasured factors cannot be fully ruled out without an RCT.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Observational cohort study
Observational cohort study (n=9) · Real-World Cohort
Biological Pathway & Modality
Receptor targeting · Enzyme · Blood biomarker
Intervention: Phase 1b study of miricorilant in patients with presumed metabolic
Experimental Findings & Endpoints
Miricorilant, an oral nonsteroidal selective glucocorticoid receptor modulator, is being investigated as a therapy that modulates hepatic cortisol activity in patients with metabolic dysfunction-associated steatohepatitis (MASH).
This phase 1b study (NCT05117489) evaluated miricorilant's efficacy and safety. Seventy patients with presumed MASH received oral miricorilant daily (30-150 mg) or intermittent (100-200 mg once, twice, or thrice weekly) dosing regimens for 12 or 24 weeks.
Across dosing regimens, reductions in relative liver fat content (LFC) ranged from a clinically meaningful level to 76.6%. Improvements in MASH liver function markers and the enhanced liver fibrosis (ELF) score were observed across regimens.
Treatment-emergent adverse events (TEAEs) leading to drug interruption/discontinuation occurred in a clinically meaningful level of patients (n=9) each; most were due to aminotransferase elevations during an excessively rapid drop in LFC (substantially at week 6) and in patients receiving daily dosing. Intermittent dosing enabled more patients to complete 12 weeks of treatment without discontinuation due to TEAEs.
Intermittent dosing with miricorilant 100 mg twice weekly had the best benefit-risk profile; this cohort demonstrated a mean LFC reduction of 28.2% at week 12, with a corresponding decline in liver enzymes (ALT, -3.8 U/L; AST, -6.0 U/L). Patients in this cohort also had numerical improvement in lipid profiles, glycemic markers, and fibrosis biomarkers.
Clinical Translation & Practice Context
Intermittent miricorilant dosing of 100 mg twice weekly achieved meaningful reductions in LFC and improved liver health markers with a favorable safety profile.
This regimen is being evaluated in the phase 2b MONARCH study (NCT06108219).
The Bottom Line · Clinical Pearl
“Intermittent miricorilant dosing of 100 mg twice weekly achieved meaningful reductions in LFC and improved liver health markers with a favorable safety profile.”
Published in Hepatology (baltimore, Md.) · Current Stage: Real-World Cohort
