Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis : ENHANCE, a phase 3, randomized, placebo-controlled study
Hirschfield, Gideon M. (University of Toronto)
Shiffman, Mitchell L. (Liver Institute of Virginia)
Gulamhusein, Aliya (University of Toronto)
Kowdley, Kris V. (Liver Institute Northwest)
Vierling, John M. (Baylor College of Medicine (Houston, Estats Units d'Amèrica))
Levy, Cynthia (University of Miami Miller School of Medicine)
Kremer, Andreas E. (University Hospital Zurich (Suïssa))
Zigmond, Ehud (Tel Aviv University)
Andreone, Pietro (University of Modena and Reggio Emilia)
Gordon, Stuart C. (Wayne State University School of Medicine)
Bowlus, Christopher L. (University of California Davis School of Medicine)
Lawitz, Eric J. (University of Texas Health San Antonio)
Aspinall, Richard J. (Queen Alexandra Hospital (Portsmouth, Regne Unit))
Pratt, Daniel S. (Massachusetts General Hospital (Boston))
Raikhelson, Karina (Saint Petersburg State University)
Gonzalez-Huezo, Maria S. (Metepec Edo Mex)
Heneghan, Michael A. (King's College Hospital National Health Service Foundation Trust, London)
Jeong, Sook-Hyang (Seoul National University Bundang Hospital)
Ladrón de Guevara, Alma L. (Center of Research and Gastroenterology)
Mayo, Marlyn J. (University of Texas Southwestern)
Dalekos, George N. (General University Hospital of Larissa (Grècia))
Drenth, Joost P.H. (Department of Gastroenterology and Hepatology, Radboudumc)
Janczewska, Ewa (Medical University of Silesia)
Leggett, Barbara A. (School of Medicine, University of Queensland)
Nevens, Frederik (Center of European Reference Network (ERN) RARE-LIVER, Leuven, Belgium)
Vargas Blasco, Víctor (Universitat Autònoma de Barcelona. Departament de Medicina)
Zuckerman, Eli (Israeli Association for the Study of the Liver)
Corpechot, Christophe (Saint-Antoine Hospital)
Fassio, Eduardo (DIM Clínica Privada, Ramos Mejía)
Hinrichsen, Holger (Gastroenterology-Hepatology Center Kiel)
Invernizzi, Pietro (University of Milano-Bicocca)
Trivedi, Palak J. (University of Birmingham)
Forman, Lisa (University of Colorado)
Jones, David E.J. (Newcastle University)
Ryder, Stephen David (Queens Medical Centre)
Swain, Mark G. (University of Calgary)
Steinberg, Alexandra (CymaBay Therapeutics, Newark, California, USA)
Boudes, Pol F. (CymaBay Therapeutics, Newark, California, USA)
Choi, Yun-Jung (CymaBay Therapeutics, Newark, California, USA)
McWherter, Charles A. (CymaBay Therapeutics, Newark, California, USA)

Data:	2023
Resum:	Patients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1. 67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57. 1%, 10 mg: 78. 2%) versus placebo (12. 5%) (p < 0. 0001). ALP normalization occurred in 5. 4% (p =0. 08) and 27. 3% (p < 0. 0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3. 14 (p =0. 02); placebo: -1. 55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23. 4% (p =0. 0008); 10 mg: 16. 7% (p =0. 03); placebo: 4%]. There were no serious treatment-related adverse events. Patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Hepatology, Vol. 78 Num. 2 (April 2023) , p. 397-415, ISSN 1527-3350

DOI: 10.1097/HEP.0000000000000395
PMID: 37386786

19 p, 2.0 MB

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