Z Gastroenterol 2025; 63(08): e375-e376
DOI: 10.1055/s-0045-1810647
Abstracts | DGVS/DGAV
Freie Vorträge

Long-term efficacy and safety of open-label seladelpar treatment in patients with primary biliary cholangitis: pooled interim results for up to 3 years from the ASSURE study

Authors

  • E J Lawitz

    1   Texas Liver Institute, University of Texas Health San Antonio, San Antonio, Vereinigte Staaten

  • P J Trivedi

    2   National Institute for Health Research Birmingham Biomedical Research Centre, Centre for Liver and Gastrointestinal Research, College of Medical and Dental Sciences, University of Birmingham, and Liver Unit, University Hospitals Birmingham Queen Elizabeth, Birmingham, Vereinigtes Königreich

  • K V Kowdley

    3   Liver Institute Northwest, Seattle, Vereinigte Staaten

  • S C Gordon

    4   Division of Hepatology, Henry Ford Hospital, Wayne State University School of Medicine, Detroit, Vereinigte Staaten
    5   Michigan State University College of Medicine, East Lansing, Vereinigte Staaten

  • C L Bowlus

    6   Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento, Vereinigte Staaten

  • M C Londoño Hurtado

    7   Liver Unit, Hospital Clínic Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spanien

  • G M Hirschfield

    8   Division of Gastroenterology and Hepatology, Toronto Centre for Liver Disease, University of Toronto, Toronto, Kanada

  • A Gulamhusein

    8   Division of Gastroenterology and Hepatology, Toronto Centre for Liver Disease, University of Toronto, Toronto, Kanada

  • M Demir

    9   Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Charité-Universitätsmedizin Berlin, Berlin, Deutschland

  • D B Crittenden

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

  • S Zhuo

    11   CymaBay Therapeutics, Inc., Fremont, Vereinigte Staaten

  • C Heusner

    11   CymaBay Therapeutics, Inc., Fremont, Vereinigte Staaten

  • C Levy

    12   Division of Digestive Health and Liver Diseases, University of Miami School of Medicine, Miami, Vereinigte Staaten
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Introduction: ASSURE (NCT03301506) is an ongoing, open-label, long-term, Phase 3 trial of seladelpar — a selective PPARδ agonist — in patients (pts) with primary biliary cholangitis rolling over from the Phase 3, placebo-controlled RESPONSE trial (NCT04620733) or with prior participation in legacy trials (Phase 3 ENHANCE [NCT03602560], CB8025-21629 [NCT02955602], CB8025-31731 [NCT03301506], CB8025-21838 [NCT04950764]). The parent studies required an inadequate response or intolerance to first-line ursodeoxycholic acid.

Objectives: Here, we report pooled interim efficacy and safety for all pts in ASSURE.

Methodology: Data cutoff: January 31, 2024; pt exposure to seladelpar in ASSURE (including exposure in pts randomized to the active treatment arm in RESPONSE) was analyzed. Key efficacy endpoints included composite biochemical response (CBR; alkaline phosphatase [ALP]<1.67×upper limit of normal [ULN], ALP decrease≥15%, and total bilirubin [TB]≤ULN) and ALP normalization. Pruritus was recorded using a numeric rating scale (NRS; 0–10) collected daily through month (M) 6; change from baseline (BL) was assessed through M6 in pts with moderate-to-severe pruritus (NRS≥4) at BL. Exposure-adjusted adverse events (AEs) were calculated for each year on study as incidence per 100 pt-years. BL was based on first exposure to seladelpar in ASSURE or RESPONSE.

Results: 337 pts received 10-mg seladelpar daily. 34 pts reached 30M on study; 90 pts had≥24M of seladelpar exposure. At BL, the mean (SD) age was 58.1 (9.7) years, 318/337 (94%) pts were female, mean (SD) ALP was 287.5 (128.4) U/L, mean (SD) TB was 0.75 (0.34) mg/dL, and 55/337 (16%) had cirrhosis. At M12, M24, and M30, 204/280 evaluable pts (73%), 90/124 (73%), and 30/37 (81%) met the CBR endpoint, respectively, and ALP normalized in 106/280 (38%), 47/124 (38%), and 15/37 (41%) pts, respectively. In the pruritus NRS, mean (SE) change from BL at 6M was−3.3 (0.24) among 99 evaluable pts. Outcomes are in [Fig. 1]. Exposure-adjusted AEs were observed in 86, 70, and 63 pts per 100 pt-years at M12, M24, and M36, respectively. There were no treatment-related serious AEs.

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Fig. 1  

Conclusion: By M30 of the long-term ASSURE study, seladelpar resulted in a durable and sustained biochemical response in 81% of pts, with an ALP normalization rate of 41%, and robust improvement in pruritus. Seladelpar continues to appear safe and well tolerated, with no new safety signals or change in frequency of AEs with up to 3 years of exposure.

Abstracts

Präsentiert in der Sitzung: Autoimmune und cholestatische Lebererkrankungen

Donnerstag, 18. September 2025, 16:30 – 18:00, Saal 3



Publication History

Article published online:
04 September 2025

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