A phase 2b/3 trial of saroglitazar in primary biliary cholangitis
In brief
Saroglitazar achieved biochemical response in 57% of patients with primary biliary cholangitis
In a 52-week randomized trial of patients who could not adequately use ursodeoxycholic acid, 56.7% receiving saroglitazar met the biochemical response target, compared with 9.8% on placebo. Alkaline phosphatase normalized in 8.2% versus none, while an itch benefit seen at 24 weeks was not sustained at one year; longer-term outcomes remain unknown.
- Journal
- Hepatology (Baltimore, Md.) (Q1)
- Published
- 26 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Raj Vuppalanchi, Alejandra Villamil, Yusuf Yilmaz, Ramazan Idilman, Beatriz Margarita Ameigeiras, Farheen Shaikh, et al.
- PMID
- 42929426
- DOI
- 10.1097/HEP.0000000000001895
Why clinicians should know about it
- Picked for Biochemistry (medical) (paper of the day, 27 October 2026): Phase III trial centered on alkaline phosphatase response
Abstract
BACKGROUND: Saroglitazar, a dual PPAR alpha/gamma agonist, improved serum alkaline phosphatase (ALP) levels in patients with primary biliary cholangitis (PBC) in a phase 2a clinical trial. METHODS: EPICS-III is a phase 2b/3 adaptive, double-blind, randomized controlled trial in patients with PBC who had an inadequate response to or were intolerant of ursodeoxycholic acid (UDCA). In phase 2b, 37 participants received placebo or saroglitazar magnesium 1 or 2 mg for 16 weeks. Saroglitazar magnesium 1 mg (0.97 mg of saroglitazar) was selected for phase 3, which randomized 148 patients to saroglitazar (n=97) or placebo (n=51) for 52 weeks. The primary endpoint was biochemical response at week 52, defined as ALP <1.67 x ULN with ≥15% reduction from baseline and total bilirubin below ULN; the key secondary endpoint was ALP normalization. RESULTS: Baseline characteristics in the phase 3 efficacy population were comparable except for higher baseline ALP and other liver biochemistries in the saroglitazar group. Biochemical response was achieved in 56.7% versus 9.8% with placebo (difference, 48.0%; 95% CI, 35.3 to 60.8; p<0.001). Among participants with baseline ALP ≤3xULN, biochemical response rates were 79.0% versus 14.3%, and 83.1% versus 14.7% in the per-protocol analysis. ALP normalization occurred in 8.2% with saroglitazar versus 0% with placebo (difference, 8.5%; 95% CI, 2.9 to 14; p=0.016). Among participants with baseline 5-D Itch score ≥12, the week-24 treatment difference was -3.2 points (95% CI, -5.66 to -0.82) but was not maintained at week 52. Adverse events occurred in 81.1% with saroglitazar versus 90.5% with placebo, and serious adverse events occurred in 6.3% and 11.1%, respectively. CONCLUSION: Saroglitazar 0.97 mg significantly improved biochemical response and ALP normalization and was well tolerated over 52 weeks.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.