GASTROENTEROLOGY & HEPATOLOGY
CONFERENCE UPDATE

MASH resolution with no worsening of liver fibrosis demonstrated by semaglutide: Interim results from the phase 3 ESSENCE trial

10 Apr 2024

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​STUDY DESIGN

Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic and progressive liver disease characterized by hepatic steatosis, inflammation, and fibrosis.1 Despite its high prevalence, effective pharmacological treatments remain limited, with current strategies primarily targeting weight reduction and glycemic control.1 Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has been extensively studied in a broad spectrum of cardiometabolic diseases, positioning it as a potential therapeutic option for MASH.1

The ESSENCE trial is an ongoing, randomized, double-blind, placebo-controlled, phase 3 study assessing the efficacy and safety of once-weekly subcutaneous semaglutide 2.4mg in patients with biopsy-confirmed MASH and fibrosis stages 2-3.1 In part 1 of the study (0-72 weeks), participants (n=800) were randomized 2:1 to receive semaglutide (n=534) or placebo (n=266) along with standard of care.1 The primary analysis was conducted on the intention-to-treat (ITT) population after 72 weeks.1 The primary endpoints of part 1 of the study included steatohepatitis resolution without worsening of liver fibrosis and liver fibrosis improvement without worsening of steatohepatitis.1 Confirmatory secondary endpoints were change in body weight, resolution of steatohepatitis with improvement in liver fibrosis, and improvement in SF-36 bodily pain.1

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FINDINGS

Primary endpoints:
  • The primary endpoints were steatohepatitis resolution without worsening liver fibrosis and liver fibrosis improvement without worsening steatohepatitis1
  • Resolution of steatohepatitis without worsening of fibrosis was achieved in 62.9% of semaglutide-treated patients vs. 34.1% in the placebo group (estimated difference in responder proportions [EDP]=28.9% points; 95% CI: 21.3-36.5; p<0.0001)1
  • Improvement in liver fibrosis without worsening of steatohepatitis was observed in 37.0% of semaglutide patients vs. 22.5% with placebo (EDP=14.4% points; 95% CI: 7.5-21.4; p<0.0001)1
Secondary endpoints:
  • Confirmatory secondary endpoints were change in body weight, resolution of steatohepatitis with improvement in liver fibrosis, and improvement in SF-36 bodily pain1
  • There was a mean change in body weight of -10.5% with semaglutide vs. -2.0% with placebo (estimated treatment difference [ETD]=-8.5% points; 95% CI: -9.6 to -7.4; p<0.0001)1
  • A higher proportion of patients treated with semaglutide experienced resolution of steatohepatitis with improvement in liver fibrosis than those treated with placebo (32.8% vs. 16.2%; EDP=16.6% points; p<0.0001)1
  • Patient-reported bodily pain (SF-36) was improved with semaglutide vs. placebo (0.9 vs. -0.5; ETD=1.3 units; 95% CI: 0.0-2.7; p=0.0488)1
Safety:
  • Adverse events (AEs) were reported in 86.3% of semaglutide-treated patients compared to 79.7% with placebo1
  • The most common AEs with semaglutide included nausea (36.3%), diarrhea (26.9%), and constipation (22.3%)1
  • Serious adverse events occurred in 13.4% of participants in both the semaglutide and placebo groups1
  • Similar proportion of patients in the semaglutide and placebo arms experienced safety focus areas such as gallbladderrelated disorders (2.5% vs. 1.5%), hepatic injury (3.6% vs. 6.3%), and cardiovascular disorders (10.8% vs. 10.6%)1

 

“Semaglutide demonstrated a safety profile consistent with previous phase 2 MASH trials and the large body of evidence for semaglutide in other indications”

Professor Philip N. Newsome

Roger Williams Institute of Liver Studies,

Faculty of Life Sciences and Medicine,

King’s College London,

Foundation for Liver Research, and King’s College Hospital,

London, United Kingdom

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References

  1. Newsome PN, et al. Phase 3 ESSENCE trial: Semaglutide in metabolic dysfunction-associated steatohepatitis. Presented at the American Association for the Study of Liver Diseases (AASLD) Annual Meeting 2024; November 15-19, 2024.

MASH
LIVER FIBROSIS
SEMAGLUTIDE

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