{
  "abstract": "Introduction In the double-blind period (DBP) of the phase II ELMWOOD trial ( NCT05627362), elafibranor (ELA) was well tolerated and improved cholestasis biochemical markers in patients with PSC compared with placebo (PBO).1 We report interim data up to 28 weeks of the ongoing ELMWOOD OLE.Methods Patients completing the DBP on PBO, ELA 80mg, or ELA 120mg were eligible to enter the OLE and receive ELA 120mg. Endpoints were treatment-emergent adverse events (TEAEs) and mean change from DBP baseline in liver biochemistry and pruritus (per Worst-Itch Numeric Rating Scale [WI NRS]) to OLE Week (W)28, and in non-invasive tests (NITs) of fibrosis (enhanced liver fibrosis [ELF] and PRO-C3) to OLE W16.Results Of 64 patients who completed the DBP, 63 (98.4%) entered the OLE; 22 (100%) continued ELA 120mg treatment, and 20 (95.2%) and 21 (100%) crossed over from PBO and ELA 80mg in the DBP, respectively. At data cutoff (September 2024), TEAEs have been reported by 31/60 (51.7%) patients in the OLE; the most common TEAEs were COVID-19, nausea, pruritus, and weight increase (4/60 [6.7%] for each). TEAEs that led to treatment discontinuation have occurred in 3/60 (5.0%) patients (patient 1: diarrhea, nausea, and vomiting; patient 2: hepatocellular carcinoma; patient 3: nausea, pruritus, and agitation); all three patients had crossed over from PBO.Patients crossing over from PBO have had reductions in alkaline phosphatase (ALP) at OLE W4 (−36.1%; n=18) and W28 (−40.6%; n=5); patients initially on ELA 80mg and 120mg maintained ALP response or achieved further reductions to W28 (−35.6% [n=7] and −46.3% [n=8], respectively). At OLE W28, reductions have been seen in alanine aminotransferase, aspartate aminotransferase, total bilirubin, and γ-glutamyl transferase in patients crossing over from PBO (−21.0%, −2.5%, −10.0%, −16.9%; n=5); maintained response or further reductions have been seen in patients initially on ELA 80mg (−33.4%, −21.7%, −26.0%, −30.0%; n=7) and ELA 120mg (−27.5%, −6.5%, −17.0%, −37.2%; n=8).Reductions in WI NRS have been observed in all groups at OLE W28 (crossover PBO: −0.10; crossover ELA 80mg: −0.90; continuous ELA 120mg: −1.28). At OLE W16, patients initially on ELA 80mg or ELA 120mg have had further reductions in NIT of fibrosis (ELF: −0.16 and −0.15; PRO-C3: −20.6% and −14.4%); these markers have stabilized or reduced in patients initially on PBO (ELF: 0.05; PRO-C3: −9.3%).Conclusion(s) ELA 120mg has been well tolerated in patients with PSC in the ELMWOOD OLE. All groups show reductions in biochemical markers of cholestasis and pruritus. Patients crossing over from PBO show stabilization or reductions in NITs of fibrosis, while patients initially on ELA show further reductions in NITs of fibrosis with continued treatment.Reference Levy C, et al. J Hepatol. 2026;84:74–85.",
  "authors": [
    {
      "affiliations": [
        "Department of Hepatology, Frimley Health NHS Foundation Trust, Surrey, United Kingdom"
      ],
      "name": "Kuldeep Cheent"
    },
    {
      "affiliations": [
        "Division of Gastroenterology and Hepatology, UC Davis School of Medicine, Sacramento, USA"
      ],
      "name": "Christopher L Bowlus"
    },
    {
      "affiliations": [
        "Schiff Center for Liver Diseases, University of Miami, Miami, USA",
        "Division of Digestive Health and Liver Diseases, University of Miami School of Medicine, Miami, USA"
      ],
      "name": "Cynthia Levy"
    },
    {
      "affiliations": [
        "NHS Humber Health Partnership, Hull University Teaching Hospitals NHS Trust, Hull, UK"
      ],
      "name": "George F Abouda"
    },
    {
      "affiliations": [
        "Advent Health Transplant Institute, Denver, USA",
        "Rocky Mountain Gastroenterology, Denver, USA"
      ],
      "name": "Bahri M Bilir"
    },
    {
      "affiliations": [
        "Liver Unit, Hospital University Vall d’Hebron, Barcelona, Spain"
      ],
      "name": "Isabel Campos-Varela"
    },
    {
      "affiliations": [
        "Department of Surgery, Oncology and Gastroenterology, University of Padova, Gastroenterology Unit, University Hospital of Padova, RARE-LIVER ERN, Padova, Italy"
      ],
      "name": "Nora Cazzagon"
    },
    {
      "affiliations": [
        "Department of Medicine, William Osler Health System, Brampton, Canada"
      ],
      "name": "Natasha Chandok"
    },
    {
      "affiliations": [
        "Clínica de Gastrenterologia, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal"
      ],
      "name": "Helena Cortez-Pinto"
    },
    {
      "affiliations": [
        "Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany"
      ],
      "name": "Münevver Demir"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Hepatology, Infectious Diseases & Intoxications, Heidelberg University Hospital, Heidelberg, Germany"
      ],
      "name": "Michael T Dill"
    },
    {
      "affiliations": [
        "Aspen Woods Clinic, Calgary, Canada"
      ],
      "name": "Bertus Eksteen"
    },
    {
      "affiliations": [
        "Division of Gastroenterology & Hepatology, Thomas Jefferson University Hospital, Philadelphia, USA"
      ],
      "name": "Jonathan M Fenkel"
    },
    {
      "affiliations": [
        "Division of Gastroenterology and Hepatology, University of British Columbia, Vancouver, Canada"
      ],
      "name": "Hin Hin Ko"
    },
    {
      "affiliations": [
        "Division of Gastroenterology and Hepatology, NYU Langone Health, New York City, USA"
      ],
      "name": "Ira M Jacobson"
    },
    {
      "affiliations": [
        "Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UK"
      ],
      "name": "Yiannis Kallis"
    },
    {
      "affiliations": [
        "Liver Institute Northwest, Seattle, USA",
        "Elson S. Floyd College of Medicine, Washington State University, USA"
      ],
      "name": "Kris V Kowdley"
    },
    {
      "affiliations": [
        "South Denver Gastroenterology, Englewood, USA"
      ],
      "name": "Marcelo Kugelmas"
    },
    {
      "affiliations": [
        "VCU School of Medicine, Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Richmond, USA"
      ],
      "name": "Velimir Luketic"
    },
    {
      "affiliations": [
        "Department of Medical Sciences, IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy"
      ],
      "name": "Alessandra Mangia"
    },
    {
      "affiliations": [
        "Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Canada"
      ],
      "name": "Aldo J Montano-Loza"
    },
    {
      "affiliations": [
        "Digestive Disorders Department, Aberdeen Royal Infirmary, Aberdeen, UK"
      ],
      "name": "Ashis Mukhopadhya"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Hospital Universitario La Paz, Madrid, Spain"
      ],
      "name": "Antonio Olveira"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, UCHealth, Colorado Springs, USA"
      ],
      "name": "Bhaktasharan C Patel"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, University Hospital of Modena, Modena, Italy"
      ],
      "name": "Antonello Pietrangelo"
    },
    {
      "affiliations": [
        "Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, USA"
      ],
      "name": "Faruq Pradhan"
    },
    {
      "affiliations": [
        "Liver Unit, Gastroenterology and Hepatology Department, CIBER-Ehd, Hospital General Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain"
      ],
      "name": "Magdalena Salcedo"
    },
    {
      "affiliations": [
        "Liver Institute of Virginia, Bon Secours Mercy Health, Richmond, USA"
      ],
      "name": "Mitchell L Shiffman"
    },
    {
      "affiliations": [
        "Goethe University Frankfurt, University Hospital, Department of Gastroenterology & Hepatology, Frankfurt/Main, Germany"
      ],
      "name": "Kathrin Sprinzl"
    },
    {
      "affiliations": [
        "Queen Elizabeth University Hospital, Glasgow, UK"
      ],
      "name": "Rachael Swann"
    },
    {
      "affiliations": [
        "Sheila Sherlock Liver Centre & UCL Institute for Liver & Digestive Health, Royal Free Hospital, London, UK"
      ],
      "name": "Douglas Thorburn"
    },
    {
      "affiliations": [
        "Clinical Professor of Medicine, University of Maryland School of Medicine, Baltimore, USA"
      ],
      "name": "Paul J Thuluvath"
    },
    {
      "affiliations": [
        "National Institute of Health and Social Care Research Birmingham Biomedical Research Centre, Centre for Liver and Gastrointestinal Research, University of Birmingham, Birmingham, UK",
        "Liver Unit, University Hospitals Birmingham, Birmingham, UK"
      ],
      "name": "Palak J Trivedi"
    },
    {
      "affiliations": [
        "Ipsen, Cambridge, USA"
      ],
      "name": "Claudia O Zein"
    },
    {
      "affiliations": [
        "Ipsen, Paris, France"
      ],
      "name": "Hugo Gomes da Silva"
    },
    {
      "affiliations": [
        "Ipsen, Cambridge, USA"
      ],
      "name": "Benjamin Miller"
    },
    {
      "affiliations": [
        "Ipsen, London, UK"
      ],
      "name": "Claire Milligan"
    },
    {
      "affiliations": [
        "Ipsen, Paris, France"
      ],
      "name": "Aude Tavenard"
    },
    {
      "affiliations": [
        "Liver Center, Department of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA"
      ],
      "name": "Alan Bonder"
    }
  ],
  "title": "O51 Long-term elafibranor in primary sclerosing cholangitis (PSC): interim safety and efficacy data from the ELMWOOD open-label extension (OLE) trial",
  "uid": "99d7de44-8650-58ce-bf69-055d2f755635"
}