{
  "abstract": "Introduction Elafibranor (ELA), a peroxisome proliferator-activated receptor (PPAR)α/PPARδ agonist, is approved as second-line treatment in patients (pts) with PBC based on phase III ELATIVE ® trial results (NCT04526665). We present findings from >3 years of ELA treatment in the ongoing ELATIVE® open-label extension (OLE).Methods Pts who completed the ELATIVE ® double-blind period (DBP) could enter the OLE and receive ELA 80mg. For pts on placebo (PBO) in the DBP, baseline (BL) was the last non-missing value before the first OLE ELA dose; for pts on ELA in the DBP, BL was DBP start. Endpoints included biochemical response (alkaline phosphatase [ALP] <1.67x upper limit of normal [ULN], with ≥15% reduction from BL, and total bilirubin [TB] ≤ULN), ALP normalization, and change in ALP, TB, albumin, gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), liver stiffness measurement (LSM), and enhanced liver fibrosis (ELF) score. Changes in fatigue (PROMIS Fatigue Short Form 7a T-Score) and pruritus (Worst-Itch Numeric Rating Scale [WI NRS]) were assessed in pts with moderate-to-severe (mod-to-sev) fatigue (PROMIS T-Score ≥60) or mod-to-sev pruritus (PBC WI NRS ≥4) at BL, respectively. Results presented descriptively. Safety outcomes reported from OLE start, up to data cut-off (DCO; May 2025).Results At DCO, 153 pts had received ELA; 108 received ELA and 45 received PBO in the DBP. 138 pts entered the OLE; 115 pts remained at DCO. Through Week (W)182, biochemical response rates were sustained (W182: 72.1%; 31/43). The proportion of pts with normal ALP remained consistent (W182: 18.6%; 8/43). The effect of ELA treatment on ALP was seen as early as W4 and was sustained and reproducible in pts crossing from PBO; at all timepoints beyond W52, over 60% of pts had reductions of ≥40% from BL (W182: 67.4%; mean change in ALP: −47.1%).Markers of hepatic function including TB and albumin remained unchanged; GGT and ALT decreased. Markers of fibrosis (LSM and ELF) were stable with ELA. Improvement in PROMIS T-scores was seen at W4 with ELA and sustained to W156 in pts with BL mod-to-sev fatigue (n=25; mean [SD] −8.5 [10.3]); similar results were observed for pruritus (WI NRS in pts with BL mod-to-sev pruritus: n=23; mean [SD] −4.1 [2.3]). No new safety signals were identified; no new cases of rhabdomyolysis, myalgia, or treatment-related creatinine phosphokinase (CPK) elevations were observed.Conclusion(s) In the ongoing ELATIVE ® OLE, ELA has led to rapid, sustained, and reproducible responses in clinically relevant biomarkers of cholestasis and fibrosis, suggesting potential for slowing disease progression. Positive effects on cholestasis, sustained improvement in pruritus and fatigue, stabilization of markers of fibrosis, and a consistent safety profile confirm ELA’s suitability for long-term PBC treatment.",
  "authors": [
    {
      "affiliations": [
        "Ipsen, London, United Kingdom"
      ],
      "name": "Amandeep Phagura"
    },
    {
      "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": [
        "Department of Gastroenterology, Ege University Faculty of Medicine, İzmir, Turkey"
      ],
      "name": "Ulus Akarca"
    },
    {
      "affiliations": [
        "Gastroenterology and Hepatology Division, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil"
      ],
      "name": "Mario Reis Alvares-da-Silva"
    },
    {
      "affiliations": [
        "Medicina Interna Metabolica, Baggiovara Hospital, Azienda Ospedaliero-Universitaria di Modena and Università di Modena e Reggio Emilia, Modena, Italy"
      ],
      "name": "Pietro Andreone"
    },
    {
      "affiliations": [
        "Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile"
      ],
      "name": "Marco Arrese"
    },
    {
      "affiliations": [
        "Division of Gastroenterology and Hepatology, UC Davis School of Medicine, Sacramento, USA"
      ],
      "name": "Christopher L Bowlus"
    },
    {
      "affiliations": [
        "Reference Center for Inflammatory Biliary Disease and Autoimmune Hepatitis, European Reference Network RARE-LIVER, Saint-Antoine Hospital & Research Center, APHP, Sorbonne University, Paris, France"
      ],
      "name": "Christophe Corpechot"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, USA"
      ],
      "name": "Hany Elbeshbeshy"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium",
        "InflaMed Centre of Excellence, Laboratory of Experimental Medicine and Paediatrics, Faculty of Medicine and Health Sciences Antwerp University, Antwerp, Belgium"
      ],
      "name": "Sven Francque"
    },
    {
      "affiliations": [
        "Institute of Liver Studies, King’s College Hospital NHS Foundation Trust, London, UK"
      ],
      "name": "Michael A Heneghan"
    },
    {
      "affiliations": [
        "Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy",
        "European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS, San Gerardo dei Tintori, Monza, Italy"
      ],
      "name": "Pietro Invernizzi"
    },
    {
      "affiliations": [
        "Division of Gastroenterology and Hepatology, NYU Langone Health, New York, USA"
      ],
      "name": "Ira M Jacobson"
    },
    {
      "affiliations": [
        "Translational and Clinical Research Institute and NIHR Newcastle Biomedical Research Center, Newcastle University, Newcastle Upon Tyne, UK"
      ],
      "name": "David Jones"
    },
    {
      "affiliations": [
        "Liver Institute Northwest, Seattle, USA",
        "Elson S. Floyd College of Medicine, Washington State University, USA"
      ],
      "name": "Kris V Kowdley"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Mediclinic Durbanville, Cape Town, South Africa",
        "Tiervlei Trial Centre, Cape Town, South Africa"
      ],
      "name": "Frederik C Kruger"
    },
    {
      "affiliations": [
        "The Texas Liver Institute, University of Texas Health, San Antonio, USA"
      ],
      "name": "Eric Lawitz"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, USA"
      ],
      "name": "Marlyn J Mayo"
    },
    {
      "affiliations": [
        "Liver Institute of Virginia, Bon Secours Mercy Health, Richmond, USA"
      ],
      "name": "Mitchell L Shiffman"
    },
    {
      "affiliations": [
        "Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa"
      ],
      "name": "Mark Sonderup"
    },
    {
      "affiliations": [
        "Liver Unit, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada"
      ],
      "name": "Mark G Swain"
    },
    {
      "affiliations": [
        "Sección de Gastroenterología, Hospital San Juan de la Serena, Coquimbo, Chile"
      ],
      "name": "José Miguel Valera"
    },
    {
      "affiliations": [
        "Liver Unit, European Reference Network RARE-LIVER, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, CiberEhd, Barcelona, Spain"
      ],
      "name": "Victor Vargas"
    },
    {
      "affiliations": [
        "Departments of Medicine and Surgery, Baylor College of Medicine, Houston, USA"
      ],
      "name": "John M Vierling"
    },
    {
      "affiliations": [
        "Hepatic Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina"
      ],
      "name": "Alejandra Villamil"
    },
    {
      "affiliations": [
        "Ipsen, Cambridge, USA"
      ],
      "name": "Lauren Olson"
    },
    {
      "affiliations": [
        "Ipsen, Cambridge, USA"
      ],
      "name": "Claire Raskino"
    },
    {
      "affiliations": [
        "Ipsen, Cambridge, USA"
      ],
      "name": "Nuno Antunes"
    },
    {
      "affiliations": [
        "Ipsen, Paris, France"
      ],
      "name": "Marwan Sleiman"
    },
    {
      "affiliations": [
        "Ipsen, Cambridge, USA"
      ],
      "name": "George Harb"
    },
    {
      "affiliations": [
        "Department of Internal Medicine II, Saarland University Medical Center, Homburg, Germany"
      ],
      "name": "Jörn M Schattenberg"
    }
  ],
  "title": "P55 Long-term elafibranor leads to biochemical and symptomatic improvements for at least 3 years in patients with primary biliary cholangitis (PBC)",
  "uid": "289ff59a-e0a0-509d-ab0e-c81c47a0bfda"
}