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Monday Poster Session

Category: Liver

P2931 - Long-Term Efficacy and Safety of Open-Label Seladelpar Treatment in Patients With Primary Biliary Cholangitis: Interim Results for 2 Years From the ASSURE Study

Monday, October 28, 2024
10:30 AM – 4:00 PM ET
Location: Exhibit Hall E
Has Audio
Palak J. Trivedi, MBBS, MRCP1, Cynthia Levy, MD2, Kris V.. Kowdley, MD, FACG3, Stuart C. Gordon, MD4, Christopher L. Bowlus, MD5, Maria Carlota Londoño Hurtado, MD6, Gideon M. Hirschfield, MD7, Aliya F. Gulamhusien, MD, MPH3, Eric J. Lawitz, MD8, Alejandra Villamil, MD9, Alma de Guevara Cetina, MD10, Marlyn J. Mayo, MD, FACG11, Ziad H. Younes, MD12, Oren Shibolet, MD13, Kidist K. Yimam, MD14, Daniel S. Pratt, MD15, Jeong Heo, MD, PhD16, Ulrike Morgera, MD17, Pietro Andreone, MD18, Andreas E. Kremer, MD19, Christophe Corpechot, MD20, Aparna Goel, MD21, Adam Peyton, DO22, Hany Elbeshbeshy, MD23, Daria B. Crittenden, MD24, Carrie Heusner, PhD24, Sarah Proehl, MD24, Shuqiong Zhou, 24, Charles A. McWherter, PhD24
1University of Birmingham, Birmingham, England, United Kingdom; 2University of Miami, Miami, FL; 3Liver Institute Northwest, Seattle, WA; 4Creighton University School of Medicine, Detroit, MI; 5University of California Davis Health, Sacramento, CA; 6The Liver Unit, Hospital Clínic 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, Catalonia, Spain; 7Toronto Centre for Liver Disease, University of Toronto, Toronto, ON, Canada; 8The Texas Liver Institute, University of Texas Health, San Antonio, TX; 9Hepatic Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Buenos Aires, Argentina; 10Centro de Investigación y Gastroenterología, Mexico City, Distrito Federal, Mexico; 11University of Texas Southwestern, Dallas, TX; 12GastroOne, Germantown, TN; 13The Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Tel Aviv, Israel; 14California Pacific Medical Center, San Francisco, CA; 15Massachusetts General Hospital, Harvard Medical School, Boston, MA; 16Pusan National University and Biomedical Research Institute, Busan, Pusan-jikhalsi, Republic of Korea; 17Outpatient Clinic, Charité, Universitätsmedizin Berlin, Berlin, Brandenburg, Germany; 18University of Modena and Reggio Emilia, Internal Medicine, Baggiovara Hospital, Modena, Emilia-Romagna, Italy; 19University Hospital, Zurich, Zurich, Switzerland; 20Reference Centre for Inflammatory Biliary Diseases and Auto-Immune Hepatitis, Saint-Antoine Hospital, Paris, Ile-de-France, France; 21Stanford University, Palo Alto, CA; 22Miami Veterans Affairs Healthcare System, Miami, FL; 23Saint Louis University School of Medicine, St. Louis, MO; 24CymaBay, a Gilead Sciences Company, Fremont, CA

Introduction: Seladelpar reduces biochemical markers of cholestasis and pruritus in patients (pts) with primary biliary cholangitis (PBC). ASSURE (NCT03301506) is an ongoing, open label, long-term Phase (Ph) 3 trial of seladelpar in pts rolling over from the Ph 3 registrational study RESPONSE (NCT04620733) or with prior participation in legacy studies (Ph 3 ENHANCE [NCT03602560], CB8025-21629 [NCT02955602], CB8025-31731 [NCT03301506], and CB8025-21838 [NCT04950764]). Here, we report interim 2-year efficacy and safety results.

Methods: Pts with insufficient response/intolerance to first-line PBC treatment ursodeoxycholic acid and past participation in a seladelpar clinical trial could enroll in ASSURE. Key endpoints were the composite biochemical response (alkaline phosphatase [ALP] < 1.67× upper limit of normal [ULN], ALP decrease ≥15%, and total bilirubin ≤ULN) and ALP normalization. Pruritus was measured via numerical rating scale (NRS; 0–10). For pts entering ASSURE from RESPONSE, baseline (BL) was entry to RESPONSE and analyzed as continuous seladelpar or crossover from placebo (PBO); legacy pts were analyzed separately, with BL defined as entry to ASSURE.

Results: As of 01/31/2024, 158 (RESPONSE) and 179 (legacy) pts received seladelpar 10 mg daily for up to 155 weeks in ASSURE. In RESPONSE, 61.7% (79/128) of seladelpar pts met the composite endpoint at 12 months (M) vs 20% (13/65) for PBO. With continued treatment in ASSURE, 61.8% (63/102) at 6M and 72.4% (21/29) at 12M met the composite endpoint. Among PBO pts crossing over to seladelpar, 75% (39/52) at 6M and 93.8% (15/16) at 12M met the composite endpoint. ALP normalized in 25% of seladelpar and 0 PBO pts at 12M in RESPONSE. With continued treatment, 33.3% (6M) and 17.2% (12M) had ALP normalization; for crossover pts, 26.9% and 50% had ALP normalization. Change from BL in pruritus NRS with seladelpar in ASSURE was similar to RESPONSE: −3.8 and −3.7 at 6M in continuous and crossover pts, respectively, corresponding to the key secondary endpoint in RESPONSE. Among legacy pts, 73.2% (120/164) and 69.7% (69/99) met the composite endpoint at 12M and 24M in ASSURE; at 12M and 24M, 42.1% and 42.4% achieved ALP normalization and change from BL in pruritus NRS was −3.8 and −3.1, respectively. There were no treatment-related serious adverse events.

Discussion: Continuous treatment with seladelpar for RESPONSE and legacy pts led to sustained effects on biochemical markers and pruritus. Seladelpar appeared safe and well tolerated with long-term use.


Disclosures:
Palak Trivedi: Bristol Myers Squibb – Grant/Research Support. CymaBay, a Gilead Sciences Company – Advisor or Review Panel Member, Consultant. Dr. Falk Pharma – Consultant. Dr. Falk Pharma – Grant/Research Support. Dr. Falk Pharma – Lecture Fees. GSK – Grant/Research Support. Intercept – Consultant. Intercept – Lecture Fees. Intercept Pharma – Grant/Research Support. Perspectum Ltd – Lecture Fees. Pliant – Consultant.
Cynthia Levy: Calliditas – Consultant. CymaBay, a Gilead Sciences Company – Consultant. GSK – Consultant. Intercept – Consultant. Ipsen – Consultant. Kowa Pharmaceuticals – Consultant. Mirum – Consultant.
Kris Kowdley: 89bio – Consultant, Grant/Research Support. AbbVie – Consultant, Grant/Research Support. Boston Pharmaceuticals – Consultant, Grant/Research Support. CymaBay, a Gilead Sciences Company – Consultant, Grant/Research Support. Enanta – Consultant, Grant/Research Support. Genfit – Consultant, Grant/Research Support. Gilead Sciences, Inc. – Consultant, Grant/Research Support. Hanmi – Consultant, Grant/Research Support. HighTide – Consultant, Grant/Research Support. Intercept – Consultant, Grant/Research Support. Ipsen – Consultant, Grant/Research Support. Madrigal – Consultant, Grant/Research Support. NGM – Consultant, Grant/Research Support. Novo Nordisk – Consultant, Grant/Research Support. TERNS – Consultant, Grant/Research Support. Viking – Consultant, Grant/Research Support.
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.
Christopher Bowlus: CymaBay, a Gilead Sciences Company – Consultant. GSK – Consultant. Invea – Consultant. Ipsen – Consultant. NGM Bio – Consultant. Pliant Therapeutics – Consultant. Viking – Grant/Research Support.
Maria Carlota Londoño Hurtado: CymaBay, a Gilead Sciences Company – Consultant, Grant/Research Support. GSK – Consultant, Grant/Research Support. Intercept – Consultant, Grant/Research Support. Ipsen – Consultant, Grant/Research Support.
Gideon Hirschfield: Chemomab LTD – Data and Safety Monitoring. CymaBay, a Gilead Sciences Company – Consultant. Escient – Consultant. GSK – Consultant. Intercept – Consultant. Ipsen – Consultant. Kowa – Consultant. Mirum – Consultant. Pfizer – Endpoint Review Committee. Pliant – Consultant.
Aliya Gulamhusien: CymaBay, a Gilead Sciences Company – Consultant. Intercept – Consultant.
Eric Lawitz: 89Bio – Consultant, Grant/Research Support. Akero – Consultant, Grant/Research Support. Alnylam – Consultant, Grant/Research Support. Amgen – Consultant, Grant/Research Support. AstraZeneca – Consultant, Grant/Research Support. Axcella Health – Consultant, Grant/Research Support. Boehringer Ingelheim – Consultant, Grant/Research Support. Bristol Myers Squibb – Consultant, Grant/Research Support. CymaBay, a Gilead Sciences Company – Consultant, Grant/Research Support. CytoDyn – Consultant, Grant/Research Support. DSM – Consultant, Grant/Research Support. Durect – Consultant, Grant/Research Support. Eli Lilly – Consultant, Grant/Research Support. Enanta – Consultant, Grant/Research Support. Enyo – Consultant, Grant/Research Support. Exalenz – Consultant, Grant/Research Support. Galectin – Consultant, Grant/Research Support. Galmed – Consultant, Grant/Research Support. Genentech – Consultant, Grant/Research Support. Genfit – Consultant, Grant/Research Support. Gilead Sciences, Inc. – Consultant, Grant/Research Support. GSK – Consultant, Grant/Research Support. Hanmi – Consultant, Grant/Research Support. Hightide – Consultant, Grant/Research Support. Intercept – Consultant, Grant/Research Support. Inventiva – Consultant, Grant/Research Support. Ipsen – Consultant, Grant/Research Support. Janssen – Consultant, Grant/Research Support. Madrigal – Consultant, Grant/Research Support. Merck & Co – Consultant, Grant/Research Support. NGM – Consultant, Grant/Research Support. Northsea – Consultant, Grant/Research Support. Novartis – Consultant, Grant/Research Support. Novo Nordisk – Consultant, Grant/Research Support. Pfizer – Consultant, Grant/Research Support. Poxel Co – Consultant, Grant/Research Support. Roche – Consultant, Grant/Research Support. Sagimet – Consultant, Grant/Research Support. Terns – Consultant, Grant/Research Support. Viking – Consultant, Grant/Research Support. Zydus – Consultant, Grant/Research Support.
Alejandra Villamil indicated no relevant financial relationships.
Alma de Guevara Cetina: Akero – Consultant, Grant/Research Support. AstraZeneca – Consultant, Grant/Research Support. CymaBay, a Gilead Sciences Company – Consultant, Grant/Research Support. Eli Lilly – Consultant, Grant/Research Support. Galectin – Consultant, Grant/Research Support. Inventiva – Consultant, Grant/Research Support. Madrigal – Consultant, Grant/Research Support. Novo Nordisk – Consultant, Grant/Research Support.
Marlyn Mayo: CymaBay, a Gilead Sciences Company – Consultant. GSK – Consultant. Intra-Sana – Consultant. Ipsen – Consultant. Mirum – Consultant. Target Pharmasolutions – Consultant.
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.
Oren Shibolet: Neopharm – Consultant. Roche – Consultant. Roche – Lecture Honoraria. Sanofi – Consultant.
Kidist Yimam: Gilead Sciences, Inc. – Honorarium.
Daniel Pratt: Mediar Therapeutics – Consultant.
Jeong Heo: AstraZeneca/MedImmune – Consultant, Grant/Research Support. Roche – Consultant, Grant/Research Support.
Ulrike Morgera indicated no relevant financial relationships.
Pietro Andreone indicated no relevant financial relationships.
Andreas Kremer: Abbvie – Consultant. Bayer – Consultant. CymaBay, a Gilead Sciences Company – Consultant. Dr. Falk Pharma – Consultant. Escient – Consultant. FMC – Consultant. Gilead Sciences, Inc. – Consultant. GSK – Consultant. Intercept – Consultant. Medscape – Consultant. Mirum – Consultant. MSD – Consultant. Myr – Consultant. Roche – Consultant. Viofor – Consultant.
Christophe Corpechot: CymaBay, a Gilead Sciences Company – Consultant. Ipsen – Consultant.
Aparna Goel: Ipsen – Advisory Committee/Board Member. Parvus Therapeutics – Advisory Committee/Board Member.
Adam Peyton: AbbVie – Advisor or Review Panel Member, Speakers Bureau. Bristol Myers Squibb – Advisor or Review Panel Member, Speakers Bureau. Gilead Sciences, Inc. – Advisor or Review Panel Member, Speakers Bureau. Merck – Advisor or Review Panel Member, Speakers Bureau.
Hany Elbeshbeshy: AbbVie – Grant/Research Support, Honorarium. CymaBay, a Gilead Sciences Company – Grant/Research Support, Honorarium. Eisai – Grant/Research Support, Honorarium. Fibronostics – Grant/Research Support, Honorarium. Genfit – Grant/Research Support, Honorarium. Gilead Sciences, Inc. – Grant/Research Support, Honorarium. Intercept – Grant/Research Support, Honorarium. Mallinkrodt – Grant/Research Support, Honorarium.
Daria Crittenden: CymaBay, a Gilead Sciences Company – Employee.
Carrie Heusner: CymaBay, a Gilead Sciences Company – Employee.
Sarah Proehl: CymaBay, a Gilead Sciences Company – Employee.
Shuqiong Zhou: CymaBay, a Gilead Sciences Company – Employee.
Charles McWherter: CymaBay, a Gilead Sciences Company – Employee.


Palak J. Trivedi, MBBS, MRCP1, Cynthia Levy, MD2, Kris V.. Kowdley, MD, FACG3, Stuart C. Gordon, MD4, Christopher L. Bowlus, MD5, Maria Carlota Londoño Hurtado, MD6, Gideon M. Hirschfield, MD7, Aliya F. Gulamhusien, MD, MPH3, Eric J. Lawitz, MD8, Alejandra Villamil, MD9, Alma de Guevara Cetina, MD10, Marlyn J. Mayo, MD, FACG11, Ziad H. Younes, MD12, Oren Shibolet, MD13, Kidist K. Yimam, MD14, Daniel S. Pratt, MD15, Jeong Heo, MD, PhD16, Ulrike Morgera, MD17, Pietro Andreone, MD18, Andreas E. Kremer, MD19, Christophe Corpechot, MD20, Aparna Goel, MD21, Adam Peyton, DO22, Hany Elbeshbeshy, MD23, Daria B. Crittenden, MD24, Carrie Heusner, PhD24, Sarah Proehl, MD24, Shuqiong Zhou, 24, Charles A. McWherter, PhD24. P2931 - Long-Term Efficacy and Safety of Open-Label Seladelpar Treatment in Patients With Primary Biliary Cholangitis: Interim Results for 2 Years From the ASSURE Study, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.