A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis

Area of Science:

• Hepatology
• Endocrinology
• Pharmacology

Background:

• Metabolic dysfunction-associated steatohepatitis (MASH) poses a significant health burden.
• Dual agonism targeting glucagon receptor and glucagon-like peptide-1 (GLP-1) receptor shows potential for MASH treatment.
• The efficacy of survodutide, a dual glucagon and GLP-1 receptor agonist, in MASH with liver fibrosis requires investigation.

Purpose of the Study:

• To evaluate the efficacy and safety of survodutide in patients with biopsy-confirmed MASH and liver fibrosis (stages F1-F3).
• To assess the impact of survodutide on histological MASH improvement and liver fibrosis.
• To determine the optimal dose of survodutide for MASH treatment.

Main Methods:

• A 48-week, randomized, double-blind, placebo-controlled phase 2 trial involving 293 participants with MASH and fibrosis.
• Participants received weekly subcutaneous injections of survodutide (2.4 mg, 4.8 mg, or 6.0 mg) or placebo.
• Primary endpoint: histologic improvement in MASH without fibrosis worsening; secondary endpoints: liver fat reduction and fibrosis improvement.

Main Results:

• Histologic MASH improvement without fibrosis worsening was observed in 47% (2.4 mg), 62% (4.8 mg), and 43% (6.0 mg) of survodutide recipients versus 14% for placebo (P<0.001).
• Significant reductions in liver fat content and improvements in liver fibrosis were noted across survodutide dose groups compared to placebo.
• Adverse events like nausea, diarrhea, and vomiting were more frequent with survodutide, but serious adverse events were similar to placebo.

Conclusions:

• Survodutide demonstrated superior efficacy compared to placebo in improving MASH without worsening fibrosis.
• The results support further investigation of survodutide in larger phase 3 trials for MASH treatment.
• Survodutide represents a potential therapeutic option for patients suffering from MASH and liver fibrosis.