29 - Change in Pruritus in Patients With Primary Biliary Cholangitis and Moderate to Severe Pruritus: A Pooled Analysis From the RESPONSE and ENHANCE Studies

David EJ.. Jones, MD¹, Cynthia Levy, MD², Andreas E.. Kremer, MD, PhD, MHBA³, Alma Ladron de Guevara Cetina, MD⁴, Alejandra M.. Villamil, MD⁵, Ewa Janczewska, MD, PhD⁶, Mordechai Rabinovitz, MD⁷, Pietro Andreone, MD⁸, Xin Qi, PhD⁹, Susheela Carroll, PhD⁹, Timothy R.. Watkins, MD, MSc⁹, Marlyn J.. Mayo, MD, FACG¹⁰
1Translational and Clinical Research Institute and Centre for Rare Disease, Newcastle University, Newcastle Upon Tyne, England, United Kingdom; 2Division of Digestive Health and Liver Diseases, Miller School of Medicine, University of Miami, Miami, FL; 3University Hospital Zürich, University of Zürich, Zürich, Zurich, Switzerland; 4Centro de Investigación y Gastroenterología, Hospital Angeles Clinica Londres, Mexico City, Distrito Federal, Mexico; 5The Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Buenos Aires, Argentina; 6Medical University of Silesia, Katowice, Slaskie, Poland; 7University of Pittsburgh, Pittsburgh, PA; 8Baggiovara Hospital, University of Modena and Reggio Emilia, Modena, Italy, Modena, Emilia-Romagna, Italy; 9Gilead Sciences, Inc., Foster City, CA; 10University of Texas Southwestern, Dallas, TX

Introduction: Primary biliary cholangitis (PBC) is a cholestatic liver disease, with pruritus occurring in up to 70% of patients (pts), which can greatly reduce quality of life. Seladelpar (SEL) is a first-in-class delpar (selective PPAR-delta agonist) indicated for the treatment of PBC combined with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as a monotherapy in pts intolerant to UDCA. In two Phase 3, placebo (PBO)-controlled trials (ENHANCE [NCT03602560], RESPONSE [NCT04620733]), SEL significantly reduced pruritus in pts with moderate to severe pruritus (MSP) at baseline (BL; numerical rating scale [NRS] ≥4). Here, we present pooled pruritus outcomes across different measures of itch in pts with PBC from RESPONSE and ENHANCE with NRS ≥4 at BL.

Methods: Pts with PBC with an inadequate response or intolerance to UDCA were randomized 1:1:1 to daily, oral SEL 5 mg, SEL 10 mg, or PBO for 52 weeks (W) in ENHANCE and 2:1 to daily, oral SEL 10 mg or PBO for 52W in RESPONSE (ENHANCE terminated early with key endpoints amended to 3 months [M]). Pooled data from pts with NRS ≥4 at BL who received SEL 10 mg or PBO in RESPONSE and at least 6M in ENHANCE were analysed. In a post hoc analysis, changes across several measures of itch (NRS, PBC-40 itch domain, and 5-D itch scale) up to 6M were assessed.

Results: Of the 126 pts with MSP, 76 and 50 pts received SEL 10 mg and PBO, respectively, in RESPONSE or ENHANCE. Most pts at BL were < 50 years old at age of PBC diagnosis (73/126) and had a history of pruritus (122/126) and fatigue (77/126). NRS, PBC-40 itch domain, and 5-D itch scale scores were similar between the SEL and PBO groups at BL. At 6M, pts who received SEL experienced greater improvements in NRS scores (mean change from BL [CFB] of −3.12 vs −2.09 for SEL and PBO, respectively, P = .0004), PBC-40 itch domain scores (mean CFB of −2.26 vs −1.37 for SEL and PBO, respectively, P = .0227), 5-D itch total scores (mean CFB of −4.85 vs −2.30 for SEL and PBO, respectively, P < .0001), and 5-D itch degree domain scores (mean CFB of −0.96 vs −0.54 for SEL and PBO, respectively, P = .0005). Overall, safety profiles in pts with pruritus in the SEL and PBO groups were similar. Adverse events occurred in 58/76 (76.3%) SEL pts and 40/50 (80%) PBO pts.

Discussion: As shown in previous studies, up to 6M of SEL treatment reduced pruritus to a greater extent vs PBO in pts with PBC who had MSP when assessed across 3 different measures of itch. SEL was well tolerated in this pt population.

Disclosures:
David Jones: CymaBay Therapeutics – Consultant. Falk – Speakers Bureau. GSK – Speakers Bureau. Intercept Pharmaceuticals – Consultant, Speakers Bureau. Ipsen – Consultant, Speakers Bureau. Kowa – Consultant. Umecrine – Consultant.
Cynthia Levy: Calliditas Therapeutics – Grant/Research Support. CymaBay Therapeutics – Grant/Research Support. Escient Pharmaceuticals – Grant/Research Support. EWR – Grant/Research Support. Gilead Sciences, Inc. – Grant/Research Support. GSK – Grant/Research Support. Intercept Pharmaceuticals – Grant/Research Support. Ipsen – Grant/Research Support. Kowa – Grant/Research Support. Mirum Pharma – Grant/Research Support. Target – Grant/Research Support. Zydus Pharmaceuticals – Grant/Research Support.
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.
Alma Ladron de Guevara Cetina: Akero Therapeutics – Grant/Research Support. AstraZeneca – Grant/Research Support. Eli Lilly – Grant/Research Support. Galectin Therapeutics – Grant/Research Support. GSK – Grant/Research Support. Inventiva – Grant/Research Support. Madrigal Pharmaceuticals – Grant/Research Support. Merck Sharp & Dohme – Grant/Research Support. Novo Nordisk – Grant/Research Support.
Alejandra Villamil: Intercept Pharmaceuticals – Speakers Bureau. Novartis – Advisory Committee/Board Member.
Ewa Janczewska: Calliditas Therapeutics – Grant/Research Support. CymaBay Therapeutics – Grant/Research Support. Dr. Falk Pharma – Grant/Research Support. Gilead Sciences, Inc. – Grant/Research Support.
Mordechai Rabinovitz indicated no relevant financial relationships.
Pietro Andreone indicated no relevant financial relationships.
Xin Qi: Gilead Sciences, Inc. – Employee, Stock Options.
Susheela Carroll: Gilead Sciences, Inc. – Employee, Stock Options.
Timothy Watkins: Gilead Sciences, Inc. – Employee, Stock Options.
Marlyn Mayo: CymaBay Therapeutics – Consultant. GSK – Consultant. Intra-Sana – Consultant. Ipsen – Consultant. Mirum Pharma – Consultant. Target Pharmasolution – Consultant.

David EJ.. Jones, MD¹, Cynthia Levy, MD², Andreas E.. Kremer, MD, PhD, MHBA³, Alma Ladron de Guevara Cetina, MD⁴, Alejandra M.. Villamil, MD⁵, Ewa Janczewska, MD, PhD⁶, Mordechai Rabinovitz, MD⁷, Pietro Andreone, MD⁸, Xin Qi, PhD⁹, Susheela Carroll, PhD⁹, Timothy R.. Watkins, MD, MSc⁹, Marlyn J.. Mayo, MD, FACG¹⁰, 29, Change in Pruritus in Patients With Primary Biliary Cholangitis and Moderate to Severe Pruritus: A Pooled Analysis From the RESPONSE and ENHANCE Studies, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.