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

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.

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Journal
Hepatology
Published
2026-11-05
DOI
https://doi.org/10.1097/hep.0000000000001906
Citations
1
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Liver Diseases and Immunity
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article
Field-Weighted Citation Impact
2.82
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article

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

Philip J.F. Troke, Antonio Olveira, Václav Hejda, Gillian Bubb et al.
1 citations
Hepatology
Liver Diseases and Immunity
2.82
article

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

Philip J.F. Troke, Antonio Olveira, Václav Hejda, Gillian Bubb, Ziad H Younes, Claire Raskino, Ashis Mukhopadhya, Benjamin W. Miller, Christopher L. Bowlus, Wonseok Kang, Sergio Rodríguez‐Tajes, Kuldeep S. Cheent, Jeong Heo, Carmen E. Landaverde, Bhaktasharan Patel, Eric Lawitz, Matthieu Guivarch, Anna Suk-Fong Lok, Jan Šperl, Kris V. Kowdley, George Harb, Valeria Cranham, Frank E. Uschner, Ana Lleo, on behalf of the ELSPIRE Trial Investigators’ Group, Byoung K. Jang, Fabian Rodas Ochoa
article en
1 citations

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.

Hepatology
Humanitas University (IT), The University of Texas at San Antonio Health Science Center (US), Washington State University Spokane (US), Ipsen (France) (FR), Charles University (CZ), University of Michigan (US), Hospital Universitario La Paz (ES), Aberdeen Royal Infirmary (GB), Samsung Medical Center (KR), Frimley Health NHS Foundation Trust (GB), University of Colorado Health (US), Ipsen (United Kingdom) (GB), NHS Grampian (GB), University Hospital Münster (DE), Michigan Medicine (US), Pusan National University Hospital (KR), Liver Institute Northwest (US), Institute of Clinical and Experimental Medicine (CZ), Gastro One (United States) (US), Texas Liver Institute (US), Clinique Pasteur (FR), Ipsen (United States) (US), University of California Davis Medical Center (US), IRCCS Humanitas Research Hospital (IT), Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (ES), Pusan National University (KR), Keimyung University (KR), Universitat de Barcelona (ES), University of California, Davis (US), Sungkyunkwan University (KR)
Openalex Percentile: Top 7%
Liver Diseases and Immunity
2.82
DOIOpen Access PDFOpenAlex
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