Semaglutide in Japanese participants with metabolic dysfunction-associated steatohepatitis: a subgroup analysis of the ESSENCE trial.

BACKGROUND: This subgroup analysis assessed the efficacy and safety of semaglutide in the Japanese subgroup versus the overall trial population of ESSENCE (part 1) and evaluated the impact of baseline characteristics. METHODS: ESSENCE is an ongoing, phase 3, multicenter, randomized, double-blind, placebo-controlled trial that includes 1197 participants with biopsy-defined metabolic dysfunction-associated steatohepatitis and liver fibrosis stage 2 or 3 randomized 2:1 to receive once-weekly subcutaneous semaglutide 2.4 mg or placebo for 240 weeks (NCT04822181). The results of an interim analysis for efficacy conducted at week 72 involving the first 800 randomized participants are reported here (part 1). RESULTS: One hundred and sixteen of the first 800 randomized participants included in the interim analysis for efficacy were Japanese and received semaglutide (n = 78) or placebo (n = 38). Compared with the overall population, Japanese participants were older and had a lower body mass index. Resolution of steatohepatitis and no worsening of liver fibrosis was achieved by 63.1 and 36.8% of Japanese participants receiving semaglutide and placebo, respectively (estimated difference in responder proportions [EDP]: 26.65 [95% confidence interval (CI): 7.43-45.86]). Improvement in liver fibrosis and no worsening of steatohepatitis was achieved by 36.5 and 28.9% of Japanese participants receiving semaglutide and placebo, respectively (EDP: 7.07 [95% CI: -11.48-25.62]). Based on the adverse event profiles of all participants receiving treatment, semaglutide was well tolerated in the Japanese population. Age and body mass index distribution did not meaningfully affect efficacy and safety. CONCLUSIONS: The efficacy and safety of semaglutide were directionally consistent in the Japanese population compared with those of the overall ESSENCE population. TRIAL REGISTRATION: ClinicalTrials.gov; https://clinicaltrials.gov/study/NCT04822181.