{
  "abstract": "Progressive familial intrahepatic cholestasis (PFIC) is a group of genetic disorders resulting in disrupted bile composition, cholestasis, and pruritus. Maralixibat, an inhibitor of the ileal bile acid transporter, is approved in the EU for the treatment of Progressive Familial Intrahepatic Cholestasis (PFIC) in individuals ≥3 months of age. In the 26-week placebo-controlled MARCH Phase 3 study, MRX at 570 μg/kg BID demonstrated significant improvements in pruritus, serum bile acids (sBA), total bilirubin (TB) and growth in patients across the broadest range of PFIC types studied to date. We report on long-term maintenance of effect of up to 2 years of treatment with MRX in MARCH-ON, an open-label, long-term extension study of MARCH.Long-term maintenance of response was assessed for patients who were originally randomized to receive MRX in MARCH and continued with treatment in MARCH-ON (MRX-MRX group: n=47), and for patients who received placebo (PBO) in the MARCH study and switched to open-label MRX in MARCH-ON (PBO-MRX group: n=41). Assessments included: pruritus, sBA, TB, growth z-scores, and incidence of treatment-emergent adverse events (TEAEs). Baseline (BL) was defined as the start of MRX for each group.For the MRX-MRX group, the median (min, max) time on MRX was 638 days (10, 1135). 13 of 47 patients reached Week 104 at time of analysis. Significant improvements observed in the first 26 weeks of the MARCH study were sustained through Week 104 in MARCH-ON for pruritus (-2.03, p<0.0001), sBA (-166 μmol/L, p=0.003), TB (-27.7 μmol/L, p=0.02), and growth (height z-score: +0.40, p=0.046; weight z-score: +0.52, p=0.01). In the PBO-MRX group, the median time on MRX was 456 days (22, 720). 18 of 41 patients reached Week 52 of MRX treatment at time of analysis. Significant improvements through Week 52 for pruritus (-1.1, p=0.0001), sBA (-71 μmol/L, p=0.03), and growth (height z-score: +0.37, p=0.01; weight z-score: +0.32, p=0.03) were in line with observations from the initial MARCH MRX group. Additionally, numeric reductions in TB (-6.4 μmol/L; p=0.7) were observed. No new safety signals were identified. The most common TEAEs were GI-related with diarrhea (50%) being mostly mild and transient.Significant and sustained improvements in pruritus, sBA, TB, and growth are observed with up to 2 years of MRX treatment across the broadest range of genetic PFIC types studied to date. These data suggest overall improved liver health with MRX treatment which can be maintained long-term.",
  "authors": [
    {
      "affiliations": [
        "Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio"
      ],
      "name": "Alexander G Miethke"
    },
    {
      "affiliations": [
        "Hôtel Dieu de France Saint Joseph University Hospital, Beirut, Lebanon"
      ],
      "name": "Adib Moukarzel"
    },
    {
      "affiliations": [
        "Hospital Sírio-Libanês, São Paulo, Brazil"
      ],
      "name": "Gilda Porta"
    },
    {
      "affiliations": [
        "Nois de México SA de CV, Jalisco, Mexico"
      ],
      "name": "Joshue Covarrubias Esquer"
    },
    {
      "affiliations": [
        "Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children’s Memorial Health Institute, Warsaw, Poland"
      ],
      "name": "Piotr Czubkowski"
    },
    {
      "affiliations": [
        "Cardioinfantil Foundation-La Cardio, Bogotá, Colombia"
      ],
      "name": "Felipe Ordonez"
    },
    {
      "affiliations": [
        "Ospedale Pediatrico Bambino Gesù Irccs, Lazio, Italy"
      ],
      "name": "Antonella Mosca"
    },
    {
      "affiliations": [
        "University of Texas Southwestern Medical Center, Dallas, Texas"
      ],
      "name": "Amal Aqul"
    },
    {
      "affiliations": [
        "UPMC Children’s Hospital of Pittsburgh, Pediatrics, Pittsburgh, Pennsylvania"
      ],
      "name": "Robert H Squires"
    },
    {
      "affiliations": [
        "UCLouvain, Cliniques Universitaires St Luc, Pediatric Hepatology, Brussels, Belgium"
      ],
      "name": "Etienne Sokal"
    },
    {
      "affiliations": [
        "Hospital Italiano de Buenos Aires, Buenos Aires, Argentina"
      ],
      "name": "Daniel D’Agostino"
    },
    {
      "affiliations": [
        "Hannover Medical School, Pediatric Gastroenterology and Hepatology, Hannover, Germany"
      ],
      "name": "Ulrich Baumann"
    },
    {
      "affiliations": [
        "Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy"
      ],
      "name": "Lorenzo D’Antiga"
    },
    {
      "affiliations": [
        "Medical University of South Carolina, Charleston, South Carolina"
      ],
      "name": "Nagraj Kasi"
    },
    {
      "affiliations": [
        "Hôpital des Enfants – CHU Toulouse, Toulouse, France"
      ],
      "name": "Nolwenn Laborde"
    },
    {
      "affiliations": [
        "Koc University School of Medicine, Istanbul, Turkey"
      ],
      "name": "Cigdem Arikan"
    },
    {
      "affiliations": [
        "Children’s Hospital Los Angeles, Los Angeles, California"
      ],
      "name": "Chuan-Hao Lin"
    },
    {
      "affiliations": [
        "University of Alberta, Pediatrics, Edmonton, Alberta, Canada"
      ],
      "name": "Susan M Gilmour"
    },
    {
      "affiliations": [
        "University of Texas Health Science Center at San Antonio, San Antonio, Texas"
      ],
      "name": "Naveen Mittal"
    },
    {
      "affiliations": [
        "KK Women’s and Children’s Hospital, Singapore"
      ],
      "name": "Fang Kuan Chiou"
    },
    {
      "affiliations": [
        "UPMC Children’s Hospital of Pittsburgh, Pediatrics, Pittsburgh, Pennsylvania"
      ],
      "name": "Simon P Horslen"
    },
    {
      "affiliations": [
        "Medical University of Vienna, Vienna, Austria"
      ],
      "name": "Wolf-Dietrich Huber"
    },
    {
      "affiliations": [
        "Mirum Pharmaceuticals, Inc., Foster City, California"
      ],
      "name": "Tiago Nunes"
    },
    {
      "affiliations": [
        "Mirum Pharmaceuticals, Inc., Foster City, California"
      ],
      "name": "Anamaria Lascau"
    },
    {
      "affiliations": [
        "Mirum Pharmaceuticals, Inc., Foster City, California"
      ],
      "name": "Lara Longpre"
    },
    {
      "affiliations": [
        "Mirum Pharmaceuticals, Inc., Foster City, California"
      ],
      "name": "Douglas B Mogul"
    },
    {
      "affiliations": [
        "Mirum Pharmaceuticals, Inc., Foster City, California"
      ],
      "name": "Marshall Baek"
    },
    {
      "affiliations": [
        "Mirum Pharmaceuticals, Inc., Foster City, California"
      ],
      "name": "Pamela Vig"
    },
    {
      "affiliations": [
        "Cleveland Clinic Children’s, Cleveland, Ohio"
      ],
      "name": "Vera F Hupertz"
    },
    {
      "affiliations": [
        "AdventHealth for Children and AdventHealth Transplant Institute, Pediatric Gastroenterology, Hepatology, and Liver Transplant, Orlando, Florida"
      ],
      "name": "Regino Gonzalez-Peralta"
    },
    {
      "affiliations": [
        "MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Washington, DC"
      ],
      "name": "Udeme Ekong"
    },
    {
      "affiliations": [
        "Birmingham Women and Children’s Hospital, Birmingham, UK"
      ],
      "name": "Jane Hartley"
    },
    {
      "affiliations": [
        "Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Pediatric Hepato Gastroenterology and Nutrition Unit, Lyon, France"
      ],
      "name": "Noemie Laverdure"
    },
    {
      "affiliations": [
        "New York University Grossman School of Medicine, New York, New York"
      ],
      "name": "Nadia Ovchinsky"
    },
    {
      "affiliations": [
        "Institute of Liver Studies, King’s College London, London, UK"
      ],
      "name": "Richard J Thompson"
    }
  ],
  "title": "OC22 Long-term maintenance of response and improved liver heath with maralixibat in patients with progressive familial intrahepatic cholestasis (PFIC): 2-year data from the MARCH-ON study",
  "uid": "07ab2b86-8458-5058-91e8-d8d0a456aa94"
}