Long-Term Efficacy and Safety of Selective PPARδ Agonist Seladelpar in Primary Biliary Cholangitis: ASSURE Interim Study Results

Cynthia Levy; Palak J Trivedi; Kris V Kowdley; Stuart C Gordon; Christopher L Bowlus; Maria Carlota Londoño; Gideon M Hirschfield; Aliya Gulamhusein; Eric J Lawitz; John M Vierling; Marlyn J Mayo; Ira M Jacobson; Andreas E Kremer; Christophe Corpechot; David Jones; Peter Buggisch; Shuqiong Zhuo; Sarah Proehl; Carrie Heusner; Charles A McWherter; Daria B Crittenden; ASSURE Investigators

doi:10.14309/ajg.0000000000003603

Long-Term Efficacy and Safety of Selective PPARδ Agonist Seladelpar in Primary Biliary Cholangitis: ASSURE Interim Study Results

Am J Gastroenterol. 2025 Jun 24. doi: 10.14309/ajg.0000000000003603. Online ahead of print.

Authors

Cynthia Levy¹, Palak J Trivedi^{2

3}, Kris V Kowdley⁴, Stuart C Gordon⁵, Christopher L Bowlus⁶, Maria Carlota Londoño⁷, Gideon M Hirschfield⁸, Aliya Gulamhusein⁸, Eric J Lawitz⁹, John M Vierling¹⁰, Marlyn J Mayo¹¹, Ira M Jacobson¹², Andreas E Kremer¹³, Christophe Corpechot¹⁴, David Jones¹⁵, Peter Buggisch¹⁶, Shuqiong Zhuo¹⁷, Sarah Proehl¹⁸, Carrie Heusner¹⁷, Charles A McWherter¹⁷, Daria B Crittenden¹⁸; ASSURE Investigators

Affiliations

¹ Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA.
² National Institute for Health Research (NIHR) Birmingham, Centre for Liver and Gastrointestinal Research, University of Birmingham, Birmingham, UK.
³ Liver Unit, University Hospitals Birmingham, Birmingham, UK.
⁴ Liver Institute Northwest, Seattle, Washington, USA.
⁵ Division of Hepatology, Henry Ford Hospital, Detroit and Michigan State University College of Human Medicine, Lansing, Michigan, USA.
⁶ Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento, California, USA.
⁷ Liver Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona, Spain.
⁸ The Autoimmune and Rare Liver Disease Programme, Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, Ontario, Canada.
⁹ Texas Liver Institute, Clinical Professor of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.
¹⁰ Departments of Medicine and Surgery, Chief of Hepatology, Baylor College of Medicine, Houston, Texas, USA.
¹¹ Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern, Dallas, Texas, USA.
¹² Department of Gastroenterology and Hepatology, NYU Langone Health, New York, New York, USA.
¹³ Department of Gastroenterology and Hepatology, University Hospital Zürich, University of Zürich, Zürich, Switzerland.
¹⁴ Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris, France.
¹⁵ Department of Hepatology and Liver Transplantation, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, UK.
¹⁶ Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany.
¹⁷ CymaBay Therapeutics, a Gilead Sciences Company, Fremont, California, USA.
¹⁸ Gilead Sciences, Foster City, California, USA .

PMID: 40553148
DOI: 10.14309/ajg.0000000000003603

Abstract

Introduction: The objective of these analyses was to evaluate interim data from the ongoing, open-label, long-term efficacy and safety ASSURE study of seladelpar, a selective peroxisome proliferator-activated receptor δ agonist, in primary biliary cholangitis.

Methods: Patients rolling over from the phase 3, randomized, placebo-controlled, 12-month RESPONSE study or with previous participation in earlier legacy seladelpar studies were enrolled. Interim evaluations included composite biochemical response (alkaline phosphatase <1.67 upper limit of normal, total bilirubin ≤ upper limit of normal, and alkaline phosphatase decrease ≥15%), pruritus numerical rating scale (NRS) change among patients with a baseline score ≥4, and safety.

Results: At interim cutoff, 337 patients were enrolled and received ≥1 seladelpar 10 mg dose: 54 placebo-treated and 104 seladelpar-treated from RESPONSE and 179 from legacy studies. The composite response rate at RESPONSE completion was 62% (79/128) with seladelpar and 20% (13/65) with placebo. After 12 months in ASSURE, among patients who rolled over from RESPONSE, response rates were 72% (21/29) in patients continuing seladelpar and 94% (15/16) in crossover seladelpar patients. In legacy trial patients, response rates were 73% (120/164) and 70% (69/99) after 12 and 24 months of treatment in ASSURE, respectively. The NRS decrease at RESPONSE completion in seladelpar-treated patients with baseline NRS ≥4 (-3.4) was maintained after 6 additional months of treatment (-3.8); changes were similar in crossover seladelpar (-3.8) and legacy patients (-3.5) after 6 months of treatment in ASSURE. No seladelpar-related serious adverse events were reported.

Discussion: Seladelpar demonstrated durable improvements in cholestatic biomarkers and pruritus in patients with primary biliary cholangitis with up to 2 years of treatment and remained overall safe with long-term use. Clinicaltrials.gov: NCT03301506.

Keywords: cholestasis; liver; peroxisome proliferator-activated receptor delta; pruritus.

Associated data

ClinicalTrials.gov/NCT03301506

Grants and funding

Gilead Sciences