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Oral Paper Presentation

Annual Scientific Meeting

Session: Plenary Session 4A - Liver

56 - Efficacy and Safety of Seladelpar in Patients With Primary Biliary Cholangitis and Compensated Liver Cirrhosis in the Open-Label, Long-Term ASSURE Safety Study: Interim Results

Wednesday, October 30, 2024
8:40 AM – 8:50 AM ET
Location: Terrace Ballroom 1
On-Demand Video
Stuart C. Gordon, MD1, Ira Jacobson, MD2, Ziad H. Younes, MD3, Marina Silveira, MD4, Joost Drenth, PhD5, Ulrike Morgera, MD6, George Dalekos, PhD7, Jeong Heo, MD, PhD8, Ke Yang, PhD9, Carrie Heusner, PhD9, Daria B. Crittenden, MD9, Charles A. McWherter, PhD9
1Creighton University School of Medicine, Detroit, MI; 2NYU Grossman School of Medicine, New York, NY; 3GastroOne, Germantown, TN; 4Yale University School of Medicine, New Haven, CT; 5Radbound University Medical Center, Nijmegan, Gelderland, Netherlands; 6Outpatient Clinic, Charité, Universitätsmedizin Berlin, Berlin, Brandenburg, Germany; 7Thessalia University Medical School, Larissa, Thessaloniki, Greece; 8Pusan National University and Biomedical Research Institute, Busan, Pusan-jikhalsi, Republic of Korea; 9CymaBay, a Gilead Sciences Company, Fremont, CA

Introduction: Seladelpar is a selective PPAR-delta agonist with anti‑cholestatic and anti-pruritic activity in patients with primary biliary cholangitis (PBC). The ongoing, international, Phase 3 ASSURE study (NCT03301506) is an open-label, long-term study of seladelpar in patients with PBC who participated in a prior seladelpar study. Here we report interim efficacy and safety results in patients with compensated cirrhosis (CC).

Methods: Patients with PBC and cirrhosis were eligible for ASSURE if they had an inadequate response/intolerance to ursodeoxycholic acid (UDCA), previously participated in a seladelpar study, and had no history of hepatic decompensation. All patients received open-label seladelpar 10 mg orally daily. As of June 29, 2023 (data cutoff), 174 patients from previous seladelpar studies (CB8025-21629, NCT02955602; CB8025-31731, NCT03301506; ENHANCE, NCT03602560; CB8025-21838, NCT04950764) had enrolled; 33 had CC at study entry. Efficacy endpoints included the composite response of alkaline phosphatase (ALP) < 1.67× the upper limit of normal (ULN), ALP decrease ≥15%, and total bilirubin ≤ULN; ALP normalization; and change from baseline (BL) in ALP, total bilirubin, gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) all at month (M) 12.

Results: Of the 33 patients with CC, most were female (91%), and the mean age was 60.4 years. Eight patients (24.2%) had portal hypertension, 93.9% were Child-Pugh (CP) class A, and 6.1% were CP‑B. Mean BL liver stiffness by FibroScan was 19.3 kPa. At BL, mean ALP was 241.9 U/L; total bilirubin was 0.92 mg/dL (27.3% >ULN). As of the data cutoff date, 23 patients with CC had completed 12M of treatment. A total of 12/23 (52.2%) patients met the composite biochemical endpoint at M12. ALP normalization occurred in 39.1% (9/23 patients) at M12, and mean percent change from BL in ALP was −38.1% (absolute change: −99.5 U/L). Reductions were also observed in GGT and ALT (percent changes from BL: −35.1% and −19.6%,) at M12; no change was observed in AST or total bilirubin. No liver- or drug-related serious adverse events (AEs) and no AE-related discontinuations occurred.

Discussion: In this interim analysis, PBC patients with CC treated with seladelpar 10 mg for 12M achieved meaningful improvements in cholestasis and markers of liver injury; seladelpar was safe and well tolerated. These findings suggest that seladelpar may offer a safe and effective therapy for PBC patients with CC.


Disclosures:
Stuart Gordon: AbbVie – Grant/Research Support. Cymabay, a Gilead company – Consultant, Grant/Research Support. DURECT – Grant/Research Support. Genfit – Grant/Research Support. Gilead Sciences, Inc. – Consultant, Grant/Research Support. GSK – Consultant, Grant/Research Support. Hightide – Grant/Research Support. Intercept Pharma – Grant/Research Support. Merck – Grant/Research Support. Mirum – Grant/Research Support. Pliant – Grant/Research Support. Viking – Grant/Research Support.
Ira Jacobson: AbbVie – Advisory Committee/Board Member, Consultant. Aligos Therapeutics – Advisory Committee/Board Member, Consultant. Altimmune – Data monitoring committee. Arbutus Biopharma – Advisory Committee/Board Member, Consultant. Arrowhead Pharmaceuticals – Data monitoring committee. Assembly Biosciences – research. Bristol Myers Squibb – research. Chronic Liver Disease Foundation – payment for manuscript preparation. Cymabay, a Gilead company – research. Eli Lilly – research. Enanta Pharmaceuticals – research. Galmed – Data monitoring committee. Genfit – research. Gilead Sciences, Inc. – Advisory Committee/Board Member, Consultant, research. GlaxoSmithKline – Data monitoring committee. Intercept Pharmaceuticals – Advisory Committee/Board Member, Consultant, research. Janssen – Advisory Committee/Board Member, Consultant, research. Merck – research. Norvo Nordisk – research. roche – Advisory Committee/Board Member, Consultant. Takeda – Data monitoring committee.
Ziad Younes: AbbVie – Grant/Research Support, Speakers Bureau. Axcella – Grant/Research Support. Bristol Myers Squibb – Grant/Research Support, Speakers Bureau. CymaBay, a Gilead Sciences Company – Grant/Research Support. Galectin – Grant/Research Support. Intercept – Consultant, Grant/Research Support, Speakers Bureau. Inventiva – Grant/Research Support. Madrigal – Consultant, Grant/Research Support. NGM – Grant/Research Support. Norvo Nordisk – Grant/Research Support. NST – Grant/Research Support. Poxel – Grant/Research Support. Sagimet – Grant/Research Support.
Marina Silveira: Cymabay, a Gilead company – Principal investigator. Genfit – Principal investigator. Gilead – Principal investigator. Novartis – Principal investigator. Pliant – Principal investigator. Target PharmaSolutions – Principal investigator.
Joost Drenth: AbbVie – Grant/Research Support. Camurus – Consultant. COIN B Study – Advisory Committee/Board Member, data safety monitoring board. Gilead Sciences, Inc. – Grant/Research Support.
Ulrike Morgera indicated no relevant financial relationships.
George Dalekos: Genkeyotex – Advisory Committee/Board Member, Principal investigator, Speakers Bureau. Pfizer – Advisor or Review Panel Member, Principal investigator, Speakers Bureau. Sobi – Advisor or Review Panel Member, Principal investigator, Speakers Bureau.
Jeong Heo: AstraZeneca/MedImmune – Consultant, Grant/Research Support. Roche – Consultant, Grant/Research Support.
Ke Yang: Cymabay, a Gilead company – Employee.
Carrie Heusner: CymaBay, a Gilead Sciences Company – Employee.
Daria Crittenden: CymaBay, a Gilead Sciences Company – Employee.
Charles McWherter: CymaBay, a Gilead Sciences Company – Employee.


Stuart C. Gordon, MD1, Ira Jacobson, MD2, Ziad H. Younes, MD3, Marina Silveira, MD4, Joost Drenth, PhD5, Ulrike Morgera, MD6, George Dalekos, PhD7, Jeong Heo, MD, PhD8, Ke Yang, PhD9, Carrie Heusner, PhD9, Daria B. Crittenden, MD9, Charles A. McWherter, PhD9, 56, Efficacy and Safety of Seladelpar in Patients With Primary Biliary Cholangitis and Compensated Liver Cirrhosis in the Open-Label, Long-Term ASSURE Safety Study: Interim Results, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.