Z Gastroenterol 2025; 63(08): e454-e455
DOI: 10.1055/s-0045-1810775
Abstracts | DGVS/DGAV
Kurzvorträge
Autoimmune und cholestatische Lebererkrankungen: neue Wege in der Behandlung Freitag, 19. September 2025, 14:45 – 16:21, Seminarraum 14 + 15

Seladelpar treatment of patients with primary biliary cholangitis improves the GLOBE score and predicts improved transplant-free survival

Authors

  • B E Hansen

    1   Division of Gastroenterology and Hepatology, Toronto Centre for Liver Disease, University of Toronto, Toronto, Kanada
    2   Department of Epidemiology, Erasmus MC, Rotterdam, Niederlande
    3   Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Kanada

  • A Teufel

    4   Section Hepatology, Section Clinical Bioinformatics, University Medical Centre Mannheim, Mannheim, Deutschland

  • S Carroll

    5   Gilead Sciences, Inc., Foster City, Vereinigte Staaten

  • Y Zhou

    5   Gilead Sciences, Inc., Foster City, Vereinigte Staaten

  • C F Murillo Perez

    5   Gilead Sciences, Inc., Foster City, Vereinigte Staaten

  • G M Hirschfield

    1   Division of Gastroenterology and Hepatology, Toronto Centre for Liver Disease, University of Toronto, Toronto, Kanada
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    Introduction: The GLOBE score is a validated risk assessment tool used to estimate transplant-free survival (TFS) in patients (pts) with primary biliary cholangitis (PBC). Seladelpar (SEL) is a first-in-class delpar (selective PPAR-delta agonist) indicated for the treatment of PBC in combination with ursodeoxycholic acid (UDCA) in pts who have an inadequate response to UDCA, or as a monotherapy in pts unable to tolerate UDCA.

    Objectives: This study evaluated the change in GLOBE score in pts with PBC on SEL from the placebo (PBO)-controlled Phase 3 RESPONSE (NCT04620733) trial and the subsequent open-label extension (ASSURE; NCT03301506).

    Methodology: Pts with PBC who received UDCA for≥12 months (M) or were intolerant to UDCA and had alkaline phosphatase (ALP)≥1.67×the upper limit of normal (ULN) and total bilirubin (TB)≤2×ULN were enrolled in RESPONSE and randomised 2:1 to receive daily SEL 10 mg or PBO. After 1 year (Y), pts were eligible for ASSURE, in which pts on PBO could switch to SEL (crossover) and pts on SEL continued treatment (continuous). Change in GLOBE score, predicted TFS, and the contributions of ALP, TB, albumin, and platelets to changes in GLOBE score were evaluated.

    Results: 193 pts were enrolled; 95% were female. At baseline (BL), mean (SD) age and duration of PBC were 57 (9.7) and 8 (6.6) years, with mean (SD) ALP: 314 (120.9) U/L; TB: 0.76 (0.31) mg/dL; albumin: 4.1 (0.26) g/dL; platelets: 242 (80.6)×103/uL; and GLOBE score: 0.32 (0.68). Mean (SD) changes in GLOBE score from BL at 3M and 1Y for pts on SEL were−0.38 (0.21) and−0.34 (0.39), respectively, vs−0.07 (0.28) and−0.01 (0.32) for pts on PBO. At 2Y, GLOBE score changes were−0.39 (0.33) and−0.42 (0.50) for pts on continuous or crossover SEL, respectively. For pts on SEL, the greatest changes in GLOBE score were attributable to the ALP component (3M,−0.20; 1Y,−0.21; 2Y,−0.19), followed by the TB component (3M,−0.11; 1Y,−0.09; 2Y,−0.13). SEL treatment for 3M, 1Y, and 2Y led to predicted changes in TFS with hazard ratios (HRs [95% CIs]) of 0.7 (0.7–0.7), 0.8 (0.7–0.9), and 0.7 (0.6–0.8) compared with BL, respectively; HRs (95% CIs) for pts on PBO at 3M and 1Y were 1.0 (0.9–1.0) and 1.0 (1.0–1.1). At 2Y, pts on crossover SEL had similar results to those on continuous SEL.

    Conclusion: SEL treatment resulted in an early decrease in GLOBE score for pts with PBC, which was maintained over 2Y and was associated with improved predicted TFS.


     

    Publication History

    Article published online:
    04 September 2025

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