DCO1 - Clinical Care and Education Oral Abstract Presentations: Phase 3 ESSENCE Trial: Semaglutide in metabolic dysfunction-associated steatohepatitis (MASH)

Blinded Abstract: Background and Aim
Semaglutide, a glucagon-like peptide-1 receptor agonist, is being studied as a treatment for metabolic dysfunction-associated steatohepatitis (MASH) in the phase-3 ESSENCE trial.

Methods
ESSENCE is an ongoing phase-3 randomized, multi-center, trial involving participants with biopsy-defined MASH and fibrosis stage F2/F3, randomized 2:1 to receive either once-weekly subcutaneous semaglutide 2.4 mg or placebo for 240-weeks. An interim analysis at week-72 of the first 800 participants evaluated the primary endpoints: resolution of steatohepatitis without worsening liver fibrosis, and improvement in liver fibrosis without worsening steatohepatitis.

Results
Of 800 participants (semaglutide [n=534; 169 F2, 365 F3] or placebo [n=266; 81 F2, 185 F3]) (Table 1), 62.9% had resolution of steatohepatitis without worsening fibrosis in semaglutide vs 34.3% in placebo, (estimated difference in responder proportions (EDP) was 28.7% (95% CI, 21.1 to 36.2; P< 0.001). Improvement in liver fibrosis without worsening steatohepatitis was achieved by 36.8% (semaglutide) and 22.4% (placebo) (EDP, 14.4%; 95% CI, 7.5 to 21.3; P< 0.001), while 32.7% (semaglutide) and 16.1% (placebo) achieved combined resolution of steatohepatitis with improvement in liver fibrosis (EDP, 16.5%; 95% CI, 10.2 to 22.8; P< 0.001). There were improvements in liver enzymes and non-invasive fibrosis markers. As expected, improvements in body weight and cardiometabolic parameters were also observed. The incidence of serious adverse events was similar in both arms.

Conclusion
In participants with MASH and moderate to advanced liver fibrosis, semaglutide 2.4 mg once-weekly demonstrated superiority vs placebo in improving histological activity and fibrosis markers. Semaglutide also improved MASH injury, fibrosis biomarkers and cardiometabolic features.