{
  "abstract": "Seladelpar is a first-in-class delpar (selective PPAR-delta agonist) indicated in the UK for the treatment of primary biliary cholangitis including pruritus in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA. RESPONSE was a Phase 3, randomised, placebo-controlled clinical trial of seladelpar in patients with inadequate response or intolerance to UDCA. Patients completing RESPONSE were eligible to roll over into ASSURE ( NCT03301506), an ongoing, open-label, long-term, Phase 3 safety trial. Here, we describe data from month 18 (month 6 of ASSURE) in patients with or without prior use of fibrates or obeticholic acid (OCA) who rolled over from RESPONSE into ASSURE.Patients received 10 mg seladelpar orally daily or placebo in RESPONSE; patients received open-label 10 mg seladelpar in ASSURE. Fibrates and OCA were prohibited during the study period and a 6-week washout was required prior to entry in RESPONSE. Data were described for patients in ASSURE with or without prior use of fibrates/OCA and based on whether they received seladelpar (continuous seladelpar patients) or placebo (crossover patients) in RESPONSE. Efficacy included the percentage of patients achieving a composite biochemical response (CBR; alkaline phosphatase [ALP] <1.67 × upper limit of normal [ULN], ALP decrease ≥15%, and total bilirubin ≤ULN). Safety assessments included adverse events (AEs) and laboratory parameters.Among patients who continued into ASSURE from RESPONSE (n = 158), 16 continuous seladelpar and 11 crossover patients reported prior use of fibrates/OCA (total, n = 27; 17%); 88 continuous seladelpar and 43 crossover patients reported no prior use of fibrates/OCA (total, n = 131; 83%). At month 18, among continuous seladelpar patients, 9/15 (60%) patients with prior fibrate/OCA use achieved a CBR vs 54/87 (62%) patients without prior fibrate/OCA use. Among crossover patients, 7/11 (64%) patients with prior fibrate/OCA use vs 32/41 (78%) patients without prior fibrate/OCA use achieved a CBR at month 6 of ASSURE. From ASSURE initiation to month 6, incidence of AEs was similar across continuous seladelpar and crossover patients, regardless of prior OCA/fibrate use; no treatment-related serious AEs were reported.In this interim analysis of continuous seladelpar and crossover patients from ASSURE, patients who reported prior use of fibrates/OCA achieved a similar sustained biochemical response with seladelpar compared with patients who reported no prior use. Seladelpar appeared safe and well tolerated in this subgroup.",
  "authors": [
    {
      "affiliations": [
        "The Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina"
      ],
      "name": "Alejandra M Villamil"
    },
    {
      "affiliations": [
        "Autoimmune and Cholestatic Liver Center, Massachusetts General Hospital, Boston, USA"
      ],
      "name": "Daniel Pratt"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, University Hospital Zürich, University of Zürich, Zürich, Switzerland"
      ],
      "name": "Andreas E Kremer"
    },
    {
      "affiliations": [
        "Gastroenterology and Hepatology Unit, University of Palermo, Palermo, Italy"
      ],
      "name": "Vincenza Calvaruso"
    },
    {
      "affiliations": [
        "Hepatology Unit, University Hospital 12 de Octubre, Madrid, Spain"
      ],
      "name": "Elena Gómez Dominguez"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Louise Missen"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Xin Qi"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Sarah Proehl"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "William T Barchuk"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Timothy R Watkins"
    },
    {
      "affiliations": [
        "Division of Hepatology, Henry Ford Hospital, Wayne State University School of Medicine, Detroit, USA",
        "Michigan State University College of Medicine, East Lansing, USA"
      ],
      "name": "Stuart C Gordon"
    }
  ],
  "title": "P29 Efficacy and safety of seladelpar in patients with primary biliary cholangitis previously treated with fibrates or obeticholic acid",
  "uid": "6cdec72d-9d44-5bd3-99fc-6360babe6bb6"
}