Recent Studies for Metabolic Dysfunction-Associated Steatohepatitis

HARMONY Trial (2023)

• Intervention: Efruxifermin (bivalent Fc-FGF21 analogue)
• Efficacy: 39% of patients in 28mg group and 41% in 50mg group achieved improvement in fibrosis ≥1 stage with no worsening of NASH vs 20% in placebo. Risk ratio of 2.3 (95% CI 1.1-4.8; p=0.025) for 28mg and 2.2 (95% CI 1.0-5.0; p=0.036) for 50mg.
• Safety: Most frequent adverse events were diarrhea (40% vs 19% placebo) and nausea (28-42% vs 23% placebo). Five patients discontinued due to adverse events, with one drug-related serious adverse event (ulcerative esophagitis). No deaths occurred.

ICONA Trial (2025)

• Intervention: Icosabutate (FFAR1/FFAR4 agonist)
• Efficacy: 23.9% achieved MASH resolution vs 14.5% placebo (p=0.13). Higher percentage achieved ≥1-stage improvement in fibrosis: 29.3% in 300mg arm (odds ratio 2.89) and 23.9% in 600mg arm (odds ratio 2.4) vs 11.3% in placebo. Improvements in biomarkers of liver damage, inflammation, and glycemic control.
• Safety: Generally safe and well tolerated with mild to moderate adverse events and no reports of drug-induced liver injury.

Efimosfermin Study (2025)

• Intervention: Efimosfermin alfa (long-acting engineered variant of FGF21)
• Efficacy: At week 12, 89% of participants had ≥30% reduction in hepatic fat fraction vs 7% with placebo. Dose-dependent response across 75mg, 150mg, and 300mg dosing groups.
• Safety: 66% experienced treatment-emergent adverse events vs 49% with placebo. Most frequent were gastrointestinal (40% vs 24% placebo), including nausea, vomiting, and diarrhea. Events typically mild-to-moderate and resolved spontaneously. No treatment-related deaths.

Pemvidutide Study (2024)

• Intervention: Pemvidutide (GLP-1/glucagon dual receptor agonist)
• Efficacy: Significant relative reductions in liver fat content.

Resmetirom Trials

• Intervention: Resmetirom (liver-targeted thyroid hormone receptor β-selective agonist)
• Efficacy: Met primary outcomes in alleviating MASH and liver fibrosis in phase-3 clinical trials. Demonstrated efficacy in reducing hepatic fat content, improving liver histology, and ameliorating biomarkers of liver damage. Also exhibits favorable effects on circulating lipids.
• Safety: Acceptable safety profile with gastrointestinal adverse events being most common, though generally mild or moderate. Long-term surveillance warranted for potential risks related to thyroid, gonadal, or bone diseases.