P1644 - Efficacy and Safety of Seladelpar in Patients With Primary Biliary Cholangitis Previously Treated With Fibrates or Obeticholic Acid

Award: ACG Presidential Poster Award

Alejandra M.. Villamil, MD¹, Daniel Pratt, MD², Andreas E.. Kremer, MD, PhD, MHBA³, Vincenza Calvaruso, MD, PhD⁴, Elena Gómez Dominguez, MD, PhD⁵, Laurie Williams, MS⁶, Xin Qi, PhD⁶, Sarah Proehl, MD⁶, William T.. Barchuk, MD⁶, Timothy R.. Watkins, MD, MSc⁶, Stuart C.. Gordon, MD⁷
1The Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Buenos Aires, Argentina; 2Autoimmune and Cholestatic Liver Center, Massachusetts General Hospital, Boston, MA; 3Department of Gastroenterology and Hepatology, University Hospital Zürich, University of Zürich, Zürich, Zurich, Switzerland; 4Gastroenterology and Hepatology Unit, University of Palermo, Palermo, Sicilia, Italy; 5Hepatology Unit, University Hospital 12 de Octubre, Madrid, Madrid, Spain; 6Gilead Sciences, Inc., Foster City, CA; 7Division of Hepatology, Henry Ford Hospital, Wayne State University School of Medicine; Michigan State University College of Medicine, Detroit, MI

Introduction: Seladelpar is a first-in-class delpar (selective PPAR-delta agonist) indicated for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid (UDCA) in patients (pts) with an inadequate response to UDCA or as monotherapy in pts unable to tolerate UDCA. RESPONSE was a Phase 3, randomised, placebo-controlled clinical trial of seladelpar in pts with inadequate response/intolerance to UDCA. Pts completing RESPONSE were eligible to roll over into ASSURE (NCT03301506), an ongoing, open-label, long-term, Phase 3 safety trial. Here, we describe data from month 18 (month 6 of ASSURE) in pts with or without prior use of fibrates or obeticholic acid (OCA) who rolled over from RESPONSE into ASSURE.

Methods: Pts received 10 mg seladelpar orally daily or placebo in RESPONSE; pts received open-label 10 mg seladelpar in ASSURE. Fibrates and OCA were prohibited during the study period and a 6-week washout was required prior to entry in RESPONSE. Data are described for pts in ASSURE with or without prior use of fibrates/OCA and based on whether they received seladelpar (continuous seladelpar pts) or placebo (crossover pts) in RESPONSE. Efficacy included the percentage of pts achieving a composite biochemical response (CBR; alkaline phosphatase [ALP] < 1.67 × upper limit of normal [ULN], ALP decrease ≥15%, and total bilirubin ≤ ULN). Safety assessments included adverse events (AEs) and laboratory parameters.

Results: Among pts who continued into ASSURE from RESPONSE (n = 158), 16 continuous seladelpar and 11 crossover pts reported prior use of fibrates/OCA (total, n = 27; 17%); 88 continuous seladelpar and 43 crossover pts reported no prior use of fibrates/OCA (total, n = 131; 83%). At month 18, among continuous seladelpar pts, 9/15 (60%) pts with prior fibrate/OCA use achieved a CBR vs 54/87 (62%) pts without prior fibrate/OCA use. Among crossover pts, 7/11 (64%) pts with prior fibrate/OCA use vs 32/41 (78%) pts without prior fibrate/OCA use achieved a CBR at month 6 of ASSURE. From ASSURE initiation to month 6, incidence of AEs was similar across continuous seladelpar and crossover pts, regardless of prior OCA/fibrate use; no treatment-related serious AEs were reported.

Discussion: In this interim analysis of continuous seladelpar and crossover pts from ASSURE, pts who reported prior use of fibrates/OCA achieved a similar sustained biochemical response with seladelpar compared with pts who reported no prior use. Seladelpar appeared safe and well tolerated in this subgroup.

Disclosures:
Alejandra Villamil: Intercept Pharmaceuticals – Speakers Bureau. Novartis – Advisory Committee/Board Member.
Daniel Pratt: Mediar Therapeutics – Consultant.
Andreas Kremer: AbbVie – Consultant, Payment or honoraria for lectures, presentations, manuscript writing, or educational events; Participation on a data dafety monitoring board, Speakers Bureau. Advanz Pharma – Consultant, Payment or honoraria for lectures, presentations, manuscript writing, or educational events; Participation on a data dafety monitoring board, Speakers Bureau. Alentis Therapeutics – Consultant, Participation on a data safety monitoring board. Alfasigma – Consultant, Participation on a data safety monitoring board. AOP Orphan Pharmaceuticals – Payment or honoraria for lectures, presentations, manuscript writing, or educational events, Speakers Bureau. Astellas – Consultant. AstraZeneca – Consultant, Participation on a data safety monitoring board. Attovia Therapeutics – Consultant. Avior Bio – Consultant, Participation on a data safety monitoring board. Böhringer-Ingelheim – Consultant. Bayer – Consultant, Payment or honoraria for lectures, presentations, manuscript writing, or educational events; Participation on a data dafety monitoring board, Speakers Bureau. Bristol Myers Squibb – Consultant, Payment or honoraria for lectures, presentations, manuscript writing, or educational events; Participation on a data dafety monitoring board, Speakers Bureau. CymaBay Therapeutics – Consultant, Payment or honoraria for lectures, presentations, manuscript writing, or educational events; Participation on a data dafety monitoring board, Speakers Bureau. Escient Pharmaceuticals – Consultant, Participation on a data safety monitoring board. Falk – Consultant, Payment or honoraria for lectures, presentations, manuscript writing, or educational events; Participation on a data dafety monitoring board, Speakers Bureau. Gilead Sciences, Inc. – Consultant, Grant/Research Support, Independent Contractor, Support for attending meetings and/or travel; Participation on a data safety monitoring board, Speakers Bureau. GSK – Consultant, Participation on a data safety monitoring board. Guidepoint – Consultant, Participation on a data safety monitoring board. Intercept Pharmaceuticals – Consultant, Grant/Research Support, Payment or honoraria for lectures, presentations, manuscript writing, or educational events; Participation on a data dafety monitoring board, Speakers Bureau. Ipsen – Consultant, Payment or honoraria for lectures, presentations, manuscript writing, or educational events; Participation on a data dafety monitoring board, Speakers Bureau. Johnson & Johnson – Payment or honoraria for lectures, presentations, manuscript writing, or educational events, Speakers Bureau. Medscape – Payment or honoraria for lectures, presentations, manuscript writing, or educational events, Speakers Bureau. Merck Sharp & Dohme – Consultant, Payment or honoraria for lectures, presentations, manuscript writing, or educational events; Participation on a data dafety monitoring board, Speakers Bureau. Mirum Pharma – Consultant, Payment or honoraria for lectures, presentations, manuscript writing, or educational events; Participation on a data dafety monitoring board, Speakers Bureau. NewBridge Pharmaceuticals – Payment or honoraria for lectures, presentations, manuscript writing, or educational events, Speakers Bureau. Novartis – Payment or honoraria for lectures, presentations, manuscript writing, or educational events, Speakers Bureau. Novo Nordisk – Consultant, Participation on a data safety monitoring board. PBC Foundation – Leadership or fiduciary role in other board, society, committee, or advocacy groups (paid or unpaid). Rectify Pharma – Consultant. Roche – Consultant, Grant/Research Support, Payment or honoraria for lectures, presentations, manuscript writing, or educational events; Participation on a data dafety monitoring board, Speakers Bureau. Swiss Association for the Study of the Liver (SASL) – Leadership or fiduciary role in other board, society, committee, or advocacy groups (paid or unpaid). Swiss Gastroenterology Society (SGG) – Leadership or fiduciary role in other board, society, committee, or advocacy groups (paid or unpaid). Swiss Hepa, and Swiss Transplant Society (STS) – Leadership or fiduciary role in other board, society, committee, or advocacy groups (paid or unpaid). Takeda – Consultant, Participation on a data safety monitoring board. Vertex Pharmaceuticals – Payment or honoraria for lectures, presentations, manuscript writing, or educational events, Speakers Bureau. Viofor – Payment or honoraria for lectures, presentations, manuscript writing, or educational events, Speakers Bureau.
Vincenza Calvaruso: AbbVie – Speakers Bureau. Advanz Pharma – Advisory Committee/Board Member, Speakers Bureau. Echosens – Speakers Bureau. Gilead Sciences, Inc. – Advisory Committee/Board Member, Speakers Bureau. Ipsen – Advisory Committee/Board Member, Speakers Bureau. Roche – Advisory Committee/Board Member, Speakers Bureau.
Elena Gómez Dominguez: Advanz Pharma – Support for attending meetings and/or travel. GSK – Advisory Committee/Board Member. Ipsen – Consultant, Payment or honoraria for lectures, presentations, manuscript writing, or educational events, Speakers Bureau.
Laurie Williams: Gilead Sciences, Inc. – Employee, Stock Options.
Xin Qi: Gilead Sciences, Inc. – Employee, Stock Options.
Sarah Proehl: Gilead Sciences, Inc. – Employee, Stock Options.
William Barchuk: Gilead Sciences, Inc. – Employee, Stock Options.
Timothy Watkins: Gilead Sciences, Inc. – Employee, Stock Options.
Stuart Gordon: AbbVie – Grant/Research Support, Independent Contractor. Arbutus Biopharma – Grant/Research Support, Independent Contractor. CymaBay Therapeutics – Advisory Committee/Board Member, Grant/Research Support, Independent Contractor. GSK – Advisory Committee/Board Member, Grant/Research Support, Independent Contractor. Ipsen – Advisory Committee/Board Member, Grant/Research Support, Independent Contractor. Mirum Pharma – Grant/Research Support, Independent Contractor.

Alejandra M.. Villamil, MD¹, Daniel Pratt, MD², Andreas E.. Kremer, MD, PhD, MHBA³, Vincenza Calvaruso, MD, PhD⁴, Elena Gómez Dominguez, MD, PhD⁵, Laurie Williams, MS⁶, Xin Qi, PhD⁶, Sarah Proehl, MD⁶, William T.. Barchuk, MD⁶, Timothy R.. Watkins, MD, MSc⁶, Stuart C.. Gordon, MD⁷. P1644 - Efficacy and Safety of Seladelpar in Patients With Primary Biliary Cholangitis Previously Treated With Fibrates or Obeticholic Acid, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.