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
In brief
Elafibranor normalized alkaline phosphatase in 85% of patients with biliary cholangitis
In a 92-patient randomized trial, 85% of people with primary biliary cholangitis and mildly elevated alkaline phosphatase reached normal levels after 52 weeks of elafibranor, compared with 23% on placebo. The drug was well tolerated, but whether this laboratory improvement leads to fewer complications or longer survival remains unknown.
- Journal
- Hepatology (Baltimore, Md.) (Q1)
- Published
- 5 November 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Kris V Kowdley, Eric Lawitz, Christopher L Bowlus, Kuldeep Cheent, Matthieu Guivarch, Vaclav Hejda, et al.
- PMID
- 42987205
- DOI
- 10.1097/HEP.0000000000001906
Why clinicians should know about it
- Picked for Biochemistry (medical) (top studies of the week, 8 November 2026): Randomized trial tests ALP normalization as biochemical treatment target
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.
Abstract as published, via PubMed.
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