3 Key Takeaways
Plain English Summary- 01Core Finding
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.
- 02Study Evidence
Tested in a randomized controlled trial (n=62) at the Phase III stage.
- 03Practical Meaning
Large Phase III clinical evidence — long-term durability and rare subgroup effects remain under study.
What This Means for You
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.
The Discovery
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 ≥a clinically meaningful level 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. 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 (inactive comparison treatment) achieved ALP normalization with ≥meaningful 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.
How It Works, Simply
This gastroenterology research focuses on receptor targeting. Researchers evaluated it using a randomized controlled trial (n=62) at the Phase III stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
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.
- 02Study Evidence
Tested in a randomized controlled trial (n=62) at the Phase III stage.
- 03Practical Meaning
Large Phase III clinical evidence — long-term durability and rare subgroup effects remain under study.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Randomized controlled trial
Randomized controlled trial (n=62) · Phase III
Biological Pathway & Modality
Receptor targeting
Intervention: Treatment with elafibranor to normalize alkaline phosphatase in patients with
Experimental Findings & Endpoints
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 ≥a clinically meaningful level 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. 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 ≥meaningful 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.
Clinical Translation & Practice Context
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.
The Bottom Line · Clinical Pearl
“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.”
Published in Hepatology (baltimore, Md.) · Current Stage: Phase III
