Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study.

"CONFLICTS OF INTEREST Gideon M. Hirschfield consults for and received payment/honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from GlaxoSmithKline, Intercept Pharma, and Ipsen. He consults for CymaBay Therapeutics, Escient, Gilead, Mirum, and Pliant. Mitchell L. Shiffman consults for, is on the speakers’ bureau for, and received grants from Intercept. He consults for and is on the speakers’ bureau for Intra-Sana. He is on the speakers’ bureau for and received grants from Cymbay. He received grants from Genfit, Hightide, and Mirum. Aliya Gulamhusein consults for and is on the speakers’ bureau for Intercept. She consults for CymaBay. Kris V. Kowdley consults for, is on the speakers’ bureau for and received grants from 89 Bio, Genfit, Gilead, Intercept, and CymbaBay. He consults for and received grants from Madrigal, Mirum, NGM, Pliant, and Zydus. He consults for and owns stock in Inipharm. He consults for Calliditas and Ipsen. He is on the speakers’ bureau for AbbVie. He received grants from GSK, Pfizer, Hanmi, HighTide, Viking, and Janssen. He receives royalties from UpToDate. He received payment for expert testimony from the Department of Justice. He participated in a data safety monitoring board or advisory board for CTI, Durect, and Labcorp. He received equipment, materials, drugs, medical writing, gifts, or other services from Sonic Insight. John M. Vierling advises and received grants from CymaBay, Intercept, Lilly, Novartis, and Sagiment. He advises Arena, Blade, Kezar, Labcorp, Fractyl, Ipsen, Moderna, and Taiwan J. He received grants from Genfit. He is a board member of and owns stock in Athenex. Cynthia Levy consults for, advises, and received grants from Cara Therapeutics, CymaBay Therapeutics, and GlaxoSmith Kline. She consults for and received grants from Calliditas, Escient, Genfit, Gilead, Intercept, Ipsen, Mirum, and Target RWE. She received grants from HighTide, Novartis, and Zydus. Andreas E. Kremer consults for, received payment/honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from, received grants from, and advises AbbVie, Bayer, CymaBay Therapeutics, Gilead, GlaxoSmithKline, Intercept Pharma, and MSD. He received payment/honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from and received grants from AOP Orphan, Bristol Myers Squibb, CMS, Dr. Falk, Eisai, Eli Lily, Janssen, Newbridge, Novartis, and Zambon. He consults for and advises Beiersdorf, Escient, FMC, Guidepoint, Medscape, Mirum, Myr, Roche, and Viofor. Ehud Zigmond advises, received lecture fees from, and received grants from Neopharm LTD. Stuart C. Gordon consults for and received grants from CymaBay, Gilead, and GSK. He received grants from AbbVie, DURECT, Genfit, Hightide, Intercept Pharma, Merck, Mirum, Pliant, and Viking. Christopher L. Bowlus consults for and received grants from CymaBay Therapeutics, Eli Lilly, and GlaxoSmithKline. He consults for BiomX, Mirum, Shire, and Trevi Therapeutics. He received grants from Arena Pharmaceuticals, Bristol Myers Squibb, Calliditas Therapeutics, Chemomab, COUR Pharmaceuticals, Genfit, Gilead, GlaxoSmithKline, Hanmi, Intercept, Novartis, NovoNordisk, Pliant, Takeda, and TARGET. Eric J. Lawitz consults for, is on the speakers’ bureau for, and received grants from Intercept. He consults for and received grants from Akero, Boheringer Ingelheim, BMS, Novo Nordisk, Metacrine, Sagimet, and Terns. He is on the speakers’ bureau for and received grants from AbbVie and Gilead. He received grants from 89Bio Inc., Allergan, Alnylam Pharmaceuticals Inc., Amgen, Ascelia Pharma, Assemblybio, AstraZeneca, Axcella Health, Biocryst Pharmaceuticals, Bird Rock Bio Inc., Conatus Pharmaceuticals, CymaBay Therapeutics, CytoDyn, DSM, Durect Corporation, Eli Lilly, Enanta Pharmaceuticals, Enyo Pharma, Exalenz Bioscience, Galectin Therapeutics, Galmed Pharmaceuticals, Genentech, Genfit, GlaxoSmithKline, Hanmi Pharmaceuticals, HighTide Biopharma, Inventiva, Janssen Pharmaceuticals, Laboratory for Advanced Medicine, Loxo Oncology, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals Inc., Northsea Therapeutics, Novartis, Pfizer, Poxel Co., Roche, Synlogic Therapeutics, Viking Therapeutics, and Zydus Pharmaceuticals. Richard J. Aspinall consults for and is on the speakers’ bureau for Norgine UK. He is on the speakers’ bureau for Intercept UK. He owns stock in CymaBay. Daniel S. Pratt consults for Mediar Therapeutics. Karina Raikhelson received payment/honoraria for lectures presentations, speakers bureaus, manuscript writing, or educational events from Abbott Laboratories GmbH, Alfasigma Rus, Binnopharm Group, Dr. Falk Pharma GmbH, JSC Nizhfarm, and JSC Pharmstandard. She received payment/honoraria for lectures presentations, speakers bureaus, manuscript writing, or educational events and was expert witness for STPF “Polisan.” She received grants from CymaBay and Novartis. Michael A. Heneghan consulting for Ipsen, Eledon, and Moderna He recieved payment/honoraria for lectures, presentations, speakers bureau, manuscript writing, or educational events from Falk, Advanz Pharma, and Intercept Pharma. He receives royalties from UpToDate. Sook-Hyang Jeong received grants from Bristol Myers Squibb, CymaBay Therapeutics, Galmed, Gilead, Hoffmann-La Roche Ltd, Intercept, and MSD. Alma L. Ladrón de Guevara received grants from AstraZeneca, Cymabay, Lilly, Madrigal, Akero, Galectin, MSD and Novo Nordisk, and Viking. Marlyn J. Mayo consults for and received grants from CymaBay Therapeutics, GlaxoSmithKline, and Mallinckrodt. She received grants from Genfit, Intercept, Mirum, and TARGET. She consults for Ipsen. She is on the speaker’s bureau for Intra-Sana. George N. Dalekos advises, is on the speakers’ bureau for, and serves as principal investigator for Genkeyotex, Pfizer, and Sobi. He advises and is on the speakers’ bureau for Ipsen and Sanofi. He is a principal investigator for Amyndas Pharmaceuticals, CymBay Therapeutics, Intercept, Novo Nordisk, Regulus Therapeutics, and Tiziana Life Sciences. Joost P.H. Drenth consults for Camurus. He received grants from AbbVie and Gilead. He is on a data safety monitoring board or advisory board for COIN B Study. Ewa Janczewska advises and received grants from Novo Nordisk and Cellaion. She is on the speakers’ bureau for and received grants from Abbvie. She is on the speakers’ bureau for Roche. She received grants from Axella, Exelixis, CymaBay, Calliditas, BMS, GSK, Janssen-Cilag, Dr. Falk, Inventiva, and MSD. Barbara A. Leggett received grants from CymaBay Therapeutics. Frederik Nevens consults for and received grants from Gilead. He consults for Abbvie, W.L. Gore, Cook Medical, TwinPharma, Intercept, Genkyotex, Camurus, Chemomab Therapeutics, Agomab Therapeutics, Novartis Pharma, Mayoly Spindler, Calliditas Therapeutics, Norgine, Takeda, and Dynacure. He received grants from Promethera Therapeutics and Ipsen. Victor Vargas consults for Genfit. He is on the speakers’ bureau for Intercept. He is on the data safety monitoring board or advisory board for Promethera Biosciences/Cellaion. He received grants from Advanz Pharma. Christophe Corpechot consults for and received grants from Intercept and CymaBay. He consults for Genkyotex/Calliditas. He received grants from Arrow Génériques, Biotest, and Gilead. Eduardo L. Fassio received grants from Gador. Eli Zuckerman consults and is a speaker for AbbVie, Gilead, GlaxoSmithKline, Janssen, Merck, Neopharm, NovoNordisk, and Roche. He is also a speaker for Bristol Meyers Squibb and Novartis. Holger Hinrichsen consults for and received payment/honoraria for lectures, presentations, and speakers bureaus from AbbVie, Gilead, and Intercept Pharma. He received payment/honoraria for lectures, presentations, and speakers bureaus Norgine. Pietro Invernizzi advises, is on the speakers’ bureau for, and received grants from Intercept. He advises Calliditas and Zydus. He received grants from Abbvie. Palak J. Trivedi consults for and advises CymaBay. David E.J. Jones consults for, is on the speakers’ bureau for, and received funding from Intercept. He consults for CymaBay Therapeutics, Kowa, and Umecrine. He is on the speakers’ bureau for Falk, GlaxoSmithKline, and Ipsen. Mark G. Swain consults for, is on the speakers’ bureau for, and received grants from Gilead. He consults for and received grants from Pfizer and Novartis. He consults for Ipsen. He is on the speakers’ bureau for Abbott. He received grants from AbbVie, Ancella, AstraZeneca, Bristol Myers Squibb, Calliditas Therapeutics, Celgene, CymaBay Therapeutics, Galectin, Genfit, GlaxoSmithKline, Intercept, and Novo Nordisk. Alexandra Steinberg owns stock, has intellectual property rights in and was employed by CymaBay Therapeutics when the work was conducted, and is employed by Carmot Therapeutics. Pol F. Boudes was employed by CymaBay Therapeutics when the work was conducted and declares a seladelpar method of use patent for PBC. He is currently employed by Galectin Therapeutics. Yun-Jung Choi is employed by CymaBay Therapeutics. Charles A. McWherter owns stock and intellectual property rights in and is employed by CymaBay. He declares a seladelpar method of use patent for PBC and for cholestatic pruritus. The remaining authors have no conflicts to report."

"FUNDING INFORMATION This study and preparation of this manuscript were funded by CymaBay Therapeutics, which had a role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. Palak J. Trivedi received institutional salary support from the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre (BRC). This paper presents independent research supported by the Birmingham NIHR BRC based at the University Hospitals Birmingham National Health Service Foundation Trust and the University of Birmingham. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health. Presentation: Hirschfield GM, Kowdley KV, Shiffman ML, et al. ENHANCE: safety and efficacy of seladelpar in patients with PBC—a phase 3 international, randomized, placebo-controlled study [AASLD abstract LO11]. Hepatology. 2020;72(suppl 1)."

"This phase 3, double-blind, randomized, placebo-controlled study was conducted at 111 sites in 21 countries. The protocol was approved by appropriate local and national institutional review boards or independent ethics committees, and the trial was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. All patients provided written informed consent. The trial was preregistered (www.clinicaltrials.gov; NCT03602560). Pol Boudes, Christopher L. Bowlus, Gideon M. Hirschfield, Cynthia Levy, Marlyn J. Mayo, Alexandra Steinberg, John M. Vierling, Charles A. McWherter, and Yun-Jung Choi provided input to study design that led to the protocol. Gideon M. Hirschfield, Charles McWherter, and Yun-Jung Choi had access to all data and reviewed and can vouch for the integrity of the data analyses."