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Abstract Details
A randomized placebo-controlled trial of elafibranor in patients with primary biliary cholangitis and incomplete response to UDCA
J Hepatol. 2021 Jan 20;S0168-8278(21)00022-2. doi: 10.1016/j.jhep.2021.01.013.Online ahead of print.
Jörn M Schattenberg1, Albert Pares2, Kris V Kowdley3, Michael A Heneghan4, Stephen Caldwell5, Daniel Pratt6, Alan Bonder7, Gideon M Hirschfield8, Cynthia Levy9, John Vierling10, David Jones11, Anne Tailleux12, Bart Staels12, Sophie Megnien13, Remy Hanf13, David Magrez13, Pascal Birman13, Velimir Luketic14
Author information
1Metabolic Liver Research Program, I. Department of Medicine, University Medical Centre Mainz, Germany. Electronic address: joern.schattenberg@unimedizin-mainz.de.
2Hospital Clinic, University of Barcelona, CIBERehd, IDIBAPS, Barcelona, Spain.
3Liver Institute Northwest, Seattle, USA.
4Institute of Liver Studies, Kings College Hospital, London, United Kingdom.
5University of Virginia, Charlottesville, Virginia, USA.
6Massachusetts General Hospital, Boston, Massachusetts, USA.
7Liver Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
8Toronto Centre for Liver Disease, University Health Network and University of Toronto, Toronto, Canada.
9Division of Hepatology, University of Miami Miller School of Medicine, Miami, Florida, USA.
10Baylor College of Medicine, Houston, Texas, USA.
11Newcastle University Medical School, Newcastle upon Tyne, United Kingdom.
12Université Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France.
13GENFIT, 885 Avenue Eugene Avinee, 59120, Loos, France.
14Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University Health System, Richmond, Virginia, USA.
Abstract
Background and aim: Patients with primary biliary cholangitis (PBC) who have an incomplete response to ursodeoxycholic acid remain at risk of disease progression. We investigated the safety and efficacy of elafibranor, a dual PPARα/δ agonist, in patients with PBC.
Methods: This 12-week, double blind phase 2 trial enrolled 45 adults with PBC who had incomplete response to ursodeoxycholic acid (alkaline phosphatase levels ≥1.67-fold the upper limit of normal (ULN). Patients were randomly assigned to elafibranor-80 mg, elafibranor-120 mg or placebo. The primary end-point was the relative change of ALP at 12 weeks (NCT03124108).
Results: Reductions of ALP at 12 weeks were -48.3±14.8% for elafibranor-80 mg (p<0.001 vs placebo), -40.6±17.4% for elafibranor-120 mg (p<0.001) and +3.2±14.8% in the placebo group. The composite endpoint of ALP≤1.67-fold the ULN, decrease of ALP >15% and total bilirubin below the ULN was achieved in 67% patients in the elafibranor-80 mg group and 79% patients in the elafibranor-120 mg group, versus 6.7% patients in the placebo group. Levels of gamma glutamyl transferase decreased by 37.0±25.5% in the elafibranor-80mg group (p<0.001), 40.0±24.1% in the elafibranor-120mg group (p<0.01) compared with no change (+0.2±26.0%) in the placebo group. Levels of disease markers such as IgM, 5'-nucleotidase or hsCRP were likewise reduced from elafibranor. Pruritus was not induced or exacerbated from elafibranor and patients with pruritus at baseline reported less pruritic symptoms at the end of treatment. All possibly drug related non-serious adverse events were mild to moderate.
Conclusion: In this randomized phase 2 trial, elafibranor was generally safe and well tolerated and significantly reduced levels of ALP, composite endpoints of bilirubin and ALP, as well as other markers of disease activity in patients with PBC and incomplete response to ursodeoxycholic acid. Data is available from the Study Sponsor Genfit SA.