Treatment with elafibranor to normalize alkaline phosphatase in patients with primary biliary cholangitis and incomplete response to ursodeoxycholic acid: Results from the phase III randomized controlled ELSPIRE trial
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: BACKGROUND AIMS: Definitions of primary biliary cholangitis (PBC) treatment response commonly include alkaline phosphatase (ALP) <1.67× upper limit of normal (ULN). However, ALP >ULN is associated with active disease and reduced transplant-free survival, whereas ALP normalization is associated with better complication-free survival. Elafibranor, a peroxisome proliferator-activated receptor (PPAR)-α/δ agonist, has been shown to be effective and well-tolerated as a second-line treatment in patients with PBC and ALP ≥1.67x ULN. We report phase III ELSPIRE trial results, evaluating the effect of one year of elafibranor treatment on ALP normalization (ALP ≤ULN; ≤120 U/L) in patients with PBC and ALP >1-<1.67× ULN after incomplete response/intolerance to ursodeoxycholic acid. APPROACH RESULTS: In ELSPIRE, 92 patients were randomized, double-blind, 2:1 to elafibranor 80 mg (n=62) or placebo (n=30) for 52 weeks, stratified by ALP at randomization (>1-≤1.33× ULN vs. >1.33-<1.67× ULN). At Week 52, 85.3% of patients receiving elafibranor achieved the primary endpoint of ALP normalization, versus 23.3% receiving placebo (treatment difference: 62.0%; 95% CI: 44.3, 79.7; p<0.0001). Least squares mean percentage change from baseline in ALP at Week 52 was -36.5% with elafibranor versus -4.2% with placebo (p<0.0001). A greater proportion of patients receiving elafibranor versus placebo achieved ALP normalization with ≥15% reduction from baseline and complete biochemical response (normal ALP, total bilirubin, transaminases, albumin, and INR). Elafibranor was well tolerated; no new safety signals were observed. CONCLUSIONS: These results support elafibranor as second-line treatment with UDCA for patients with PBC and ALP >1-<1.67× ULN, with ALP normalization as an achievable treatment goal.
Source: Hepatology
Authors: Kris V. Kowdley, Eric Lawitz, Christopher L. Bowlus, Kuldeep Cheent, Matthieu Guivarch, Vaclav Hejda, Jeong Heo, Byoung K. Jang, Wonseok Kang, Carmen Landaverde, Anna S. Lok, Ashis Mukhopadhya, Antonio Olveira, Bhaktasharan Patel, Fabian Rodas Ochoa, Sergio Rodríguez-Tajes, Jan Sperl, Frank E. Uschner, Ziad Younes, Gillian Bubb, Valeria Cranham, George Harb, Claire Raskino, Philip J. F. Troke, Benjamin Miller, Ana Lleo, on behalf of the ELSPIRE Trial Investigators’ Group
Institutions: Washington State University Spokane, Liver Institute Northwest, The University of Texas at San Antonio Health Science Center, Texas Liver Institute, University of California Davis Medical Center, University of California, Davis, Frimley Health NHS Foundation Trust, Clinique Pasteur, Charles University, Pusan National University Hospital, Pusan National University, Keimyung University, Samsung Medical Center, Sungkyunkwan University, University of Michigan, Michigan Medicine, Aberdeen Royal Infirmary, NHS Grampian, Hospital Universitario La Paz, University of Colorado Health, Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Institute of Clinical and Experimental Medicine, University Hospital Münster, Gastro One (United States), Ipsen (United Kingdom), Ipsen (France), Ipsen (United States), Humanitas University, IRCCS Humanitas Research Hospital
Language: English
Topic: Liver Diseases and Immunity
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,900
OpenAlex ID: W7225347856