{
  "abstract": "Background Semaglutide is being investigated for its potential to treat MASH in the ongoing ESSENCE trial ( NCT04822181).Methods ESSENCE, a phase 3 trial involving 1200 participants with biopsy-defined F2/F3 MASH, randomised participants 2:1 to once-weekly subcutaneous semaglutide 2.4 mg or placebo for 240 weeks. An analysis at week 72 (part 1) of the first 800 participants evaluated co-primary end-points: resolution of steatohepatitis with no worsening of liver fibrosis, and improvement in liver fibrosis with no worsening of steatohepatitis.A secondary analysis of part 1 evaluated treatment response through assessment of histology and non-invasive tests (NITs). Those with available measurements for NITs and histology results (N = 394) were assessed for disease activity-related response: decrease in alanine transaminase (ALT) levels (≥ 25% from baseline) or improvement in FibroScan-AST (FAST) score (≥ 0.22 points from baseline). For NITs and fibrosis-related histology (N = 494), response was assessed by decrease in vibration-controlled transient elastography (LSM-VCTE) ≥ 30% from baseline or enhanced liver fibrosis (ELF) score decrease (≥ 0.5units from base-line).Results Among the 800 participants (semaglutide [n=534; 169 F2, 365 F3] or placebo [n=266; 81 F2, 185 F3]), mean (standard deviation) age was 56.0 (11.6) years. Resolution of steatohepatitis with no worsening of fibrosis was achieved by 62.9% (semaglutide) vs 34.3% (placebo) with an estimated difference in responder proportions (EDP) of 28.7% (95% CI, 21.1 to 36.2; P<0.001). Improvement in liver fibrosis with no worsening of steatohepatitis was achieved by 36.8% (semaglutide) and 22.4% (placebo) (EDP, 14.4%; 95% CI, 7.5 to 21.3; P<0.001).In the secondary analysis, evaluating disease activity in the semaglutide (n = 269) and place-bo (n = 125) arms, 90.3% vs 59.2% met at least one treatment response criteria of disease activity, respectively. The percentage that met all response criteria (ALT, FAST, histology) was 45.7% (semaglutide) vs 10.4% (placebo).In the semaglutide arm (n = 332), 84.3% met at least one of the treatment response criteria related to fibrosis, compared with 54.9% in the placebo arm (n = 162). The percentage that met all response criteria (ELF, LSM-VCTE, histology) was 16% (semaglutide) vs 5.6% (pla-cebo).The incidence of serious adverse events in the safety analysis set was similar in both arms.Conclusions In participants with F2-F3 MASH, semaglutide 2.4 mg demonstrated superiority vs placebo for improvement of histological activity and fibrosis markers. Secondary analysis showed a higher proportion of participants who received semaglutide met the NIT and histology-based definitions of treatment response vs placebo.",
  "authors": [
    {
      "affiliations": [
        "Roger Williams Institute of Liver Studies, King’s College London, London, UK"
      ],
      "name": "Philip Newsome"
    },
    {
      "affiliations": [
        "Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, VCU School of Medicine, Richmond, USA"
      ],
      "name": "Arun Sanyal"
    },
    {
      "affiliations": [
        "Novo Nordisk A/S, Copenhagen, Denmark"
      ],
      "name": "Iris Kliers"
    },
    {
      "affiliations": [
        "Novo Nordisk A/S, Copenhagen, Denmark"
      ],
      "name": "Laura Harms Østergaard"
    },
    {
      "affiliations": [
        "Novo Nordisk A/S, Copenhagen, Denmark"
      ],
      "name": "Michelle Long"
    },
    {
      "affiliations": [
        "Novo Nordisk A/S, Copenhagen, Denmark"
      ],
      "name": "Mette Skalshøi Kjær"
    },
    {
      "affiliations": [
        "Novo Nordisk A/S, Copenhagen, Denmark"
      ],
      "name": "Anna Cali"
    },
    {
      "affiliations": [
        "Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, USA"
      ],
      "name": "Manal F Abdelmalek"
    },
    {
      "affiliations": [
        "Department of Medical Sciences, University of Turin, Turin, Italy"
      ],
      "name": "Elisabetta Bugianesi"
    },
    {
      "affiliations": [
        "Université Paris Cité, INSERM UMR1149, Centre de Recherche sur l’Inflammation, Paris, France"
      ],
      "name": "Laurent Castera"
    },
    {
      "affiliations": [
        "Novo Nordisk A/S, Copenhagen, Denmark"
      ],
      "name": "Kristiane Engebresten"
    },
    {
      "affiliations": [
        "Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, University of Sydney, Sydney, Australia"
      ],
      "name": "Jacob George"
    },
    {
      "affiliations": [
        "Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, Malaysia"
      ],
      "name": "Wah Kheong Chan"
    },
    {
      "affiliations": [
        "Departamento de Gastroenterologia, Hospital das Clínicas (LIM07) da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil"
      ],
      "name": "Claudia Oliveira"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens ‘Laiko’, Athens, Greece"
      ],
      "name": "George Papatheodoridis"
    },
    {
      "affiliations": [
        "Novo Nordisk A/S, Copenhagen, Denmark"
      ],
      "name": "Ashan Shoeb"
    },
    {
      "affiliations": [
        "Sezione di Gastroenterologia, PROMISE, University of Palermo, Italy"
      ],
      "name": "Salvatore Petta"
    },
    {
      "affiliations": [
        "Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Dusseldorf, Germany"
      ],
      "name": "Michael Roden"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Turkey"
      ],
      "name": "Yusuf Yilmaz"
    },
    {
      "affiliations": [
        "Sorbonne Université, Institute for Cardiometabolism and Nutrition, Hospital Pitié-Salpêtrière, INSERM UMRS 1138 CRC, Paris, France"
      ],
      "name": "Vlad Ratziu"
    },
    {
      "affiliations": [
        "Division of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, USA"
      ],
      "name": "Mary Rinella"
    }
  ],
  "title": "P1 Phase 3 ESSENCE trial evaluating semaglutide in metabolic dysfunction-associated steatohepatitis (MASH): part 1 results and secondary analysis",
  "uid": "2ced763f-ca39-5c3f-8544-dc06f60375a3"
}