P55 Long-term elafibranor leads to biochemical and symptomatic improvements for at least 3 years in patients with primary biliary cholangitis (PBC)
Year: 2026
Type: conference-abstract
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.
Source: E-Posters
Authors: Amandeep Phagura, Cynthia Levy, Ulus Akarca, Mario Reis Alvares-da-Silva, Pietro Andreone, Marco Arrese, Christopher L Bowlus, Christophe Corpechot, Hany Elbeshbeshy, Sven Francque, Michael A Heneghan, Pietro Invernizzi, Ira M Jacobson, David Jones, Kris V Kowdley, Frederik C Kruger, Eric Lawitz, Marlyn J Mayo, Mitchell L Shiffman, Mark Sonderup, Mark G Swain, José Miguel Valera, Victor Vargas, John M Vierling, Alejandra Villamil, Lauren Olson, Claire Raskino, Nuno Antunes, Marwan Sleiman, George Harb, Jörn M Schattenberg
Institutions: Ipsen (United Kingdom), University of Miami, University of Miami Health System, Ege University, Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, Pontificia Universidad Católica de Chile, University of California Davis Medical Center, University of California, Davis, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Hôpital Saint-Antoine, Centre de Recherche Saint-Antoine, Saint Louis University, University of Antwerp, Antwerp University Hospital, King's College Hospital NHS Foundation Trust, King's College Hospital, University of Milano-Bicocca, NYU Langone Health, NIHR Newcastle Biomedical Research Centre, Newcastle University, Liver Institute Northwest, Washington State University, The University of Texas at San Antonio Health Science Center, Texas Liver Institute, The University of Texas Southwestern Medical Center, Bon Secours Mercy Health, Bon Secours Liver Institute of Richmond, University of Cape Town, Groote Schuur Hospital, University of Calgary, Universitat Autònoma de Barcelona, Vall d'Hebron Hospital Universitari, Baylor College of Medicine, Hospital Italiano de Buenos Aires, Ipsen (France), Universitätsklinikum des Saarlandes
Language: English
Topic: Liver Diseases and Immunity
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: University of Miami, Washington State University, Saint Louis University, King's College Hospital NHS Foundation Trust, National Institute for Health and Care Research, King's College London, Newcastle University, Università degli Studi di Milano-Bicocca, Ege Üniversitesi, Universidade Federal do Rio Grande do Sul, Assistance publique-Hôpitaux de Paris, Ipsen, Sorbonne Université, University of California, Davis, Faculty of Medicine and Health, University of Sydney
OpenAlex ID: W7165675231