{
  "abstract": "Introduction Seladelpar (SEL) is a first-in-class delpar (PPAR-delta agonist) indicated for the treatment of primary biliary cholangitis (PBC), including pruritus, in adults in combination with ursodeoxycholic acid (UDCA) who have an inadequate response to UDCA alone, or as monotherapy in those unable to tolerate UDCA. While SEL’s efficacy in improving cholestatic markers is well established, its impact on liver stiffness measurements (LSMs), which typically worsen over time in PBC, remains underexplored. We report longitudinal LSM data in patients treated with SEL for up to 36 months (M) in an interim analysis of the ongoing, open-label Phase 3 ASSURE study ( NCT03301506).Methods Patients enrolled in ASSURE from the placebo-controlled Phase 3 RESPONSE trial ( NCT04620733) or earlier legacy SEL studies. LSM assessed by vibration-controlled transient elastography (FibroScan) was collected as an exploratory endpoint with local reads. This analysis included on-treatment LSM from patients with ≥1 post-baseline measurement, excluding values with a confirmed IQR/LSM ratio >30%. Baseline was defined at the time of SEL initiation. Patients were stratified by baseline LSM categories: <10.7, ≥10.7 and <16.9, and ≥16.9 kPa. LSM changes were assessed at 12M, 24M, and 36M, with category shifts assessed at 36M. Due to the non-normal distribution of LSM values, medians were reported. Data cutoff: Jan 31, 2025.Results A total of 311 patients were included in the analysis. LSM values at 36M were available in 114 patients. The overall median (IQR) LSM at baseline was 7.5 (5.9, 11.1) kPa. The median change in LSM was −0.2 (−1.7, 1.8) kPa, with a percent change of −2.9% (−22.8%, 25.9%). In patients with baseline LSM of <10.7 kPa, ≥10.7 and <16.9 kPa, or ≥16.9 kPa, median changes in LSM to 36M were +0.1 (−1.3, 1.8) kPa, −0.9 (−3.6, 4.8) kPa, and −5.2 (−10.6, 2.4) kPa, respectively ( figure 1). Similarly, median percent changes from baseline were +2.0% (−18.3, 26.1), −7.4% (−29.5, 38.7), and −29.7% (−51.5, 12.7). For category shifts, most patients (97/114 [85%]) were stable or improved at 36M. Patients whose LSM worsened by 30% or more from baseline were younger (P <0.05), with otherwise comparable characteristics.Conclusions In this interim analysis, most patients maintained or improved their LSM category over 36M of SEL treatment. In the group at the highest risk for progression (≥16.9 kPa), there was a trend towards improvement with SEL.Abstract P54 Figure 1Changes in liver stiffness by baseline subgroups.Baseline was defined at the time of seladelpar initiation.n = the number of evaluable patients at each time point.BL, baseline; IQR, interquartile range; LSM, liver stiffness measure.",
  "authors": [
    {
      "affiliations": [
        "Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento, USA"
      ],
      "name": "Christopher Bowlus"
    },
    {
      "affiliations": [
        "The Autoimmune and Rare Liver Disease Programme, Toronto General Hospital, Toronto, Canada"
      ],
      "name": "Gideon Hirschfield"
    },
    {
      "affiliations": [
        "The Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina"
      ],
      "name": "Alejandra Villamil"
    },
    {
      "affiliations": [
        "Liver Institute Northwest, Seattle, USA"
      ],
      "name": "Kris Kowdley"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, USA"
      ],
      "name": "Hany Elbeshbeshy"
    },
    {
      "affiliations": [
        "Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults (FILFOIE), European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris, France"
      ],
      "name": "Christophe Corpechot"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, University Hospital Zürich, University of Zürich, Zürich, Switzerland"
      ],
      "name": "Andreas Kremer"
    },
    {
      "affiliations": [
        "National Institute for Health Research Birmingham Biomedical Research Centre, Centre for Liver and Gastrointestinal Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK, and Liver Unit, University Hospitals Birmingham Queen Elizabeth, Birmingham, UK"
      ],
      "name": "Palak Trivedi"
    },
    {
      "affiliations": [
        "Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UK"
      ],
      "name": "Yiannis Kallis"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea"
      ],
      "name": "Sook-Hyang Jeong"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Kyung Min Kwon"
    },
    {
      "affiliations": [
        "Echosens, Paris, France"
      ],
      "name": "Victor de Ledinghen"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Xin Qi"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Daria Crittenden"
    },
    {
      "affiliations": [
        "Division of Digestive Health and Liver Diseases, Miller School of Medicine, University of Miami, Miami, USA"
      ],
      "name": "Cynthia Levy"
    }
  ],
  "title": "P54 36 months of treatment with seladelpar is associated with stable or improved liver stiffness in patients with primary biliary cholangitis",
  "uid": "dcac5ef8-f9d3-5739-bc00-21e6989246c6"
}