3 Key Takeaways
Plain English Summary- 01Core Finding
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.
- 02Study Evidence
Tested in a randomized controlled trial (n=97) 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
Saroglitazar 0.97 mg significantly improved biochemical response and ALP normalization and was well tolerated over 52 weeks.
The Discovery
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. 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 (inactive comparison treatment) 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 ≥meaningful reduction from baseline and total bilirubin below ULN; the key secondary endpoint was ALP normalization. Baseline characteristics in the Phase 3 efficacy (real-world effectiveness in the trial) 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 a clinically meaningful level 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.
How It Works, Simply
This gastroenterology research focuses on mucosal barrier & gut microbiome modulation. Researchers evaluated it using a randomized controlled trial (n=97) at the Phase III stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
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.
- 02Study Evidence
Tested in a randomized controlled trial (n=97) 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=97) · Phase III
Biological Pathway & Modality
Mucosal barrier & gut microbiome modulation
Intervention: A phase 2b/3 trial of saroglitazar in primary biliary cholangitis
Experimental Findings & Endpoints
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.
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 ≥meaningful reduction from baseline and total bilirubin below ULN; the key secondary endpoint was ALP normalization.
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 a clinically meaningful level 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.
Clinical Translation & Practice Context
Saroglitazar 0.97 mg significantly improved biochemical response and ALP normalization and was well tolerated over 52 weeks.
The Bottom Line · Clinical Pearl
“Saroglitazar 0.97 mg significantly improved biochemical response and ALP normalization and was well tolerated over 52 weeks.”
Published in Hepatology (baltimore, Md.) · Current Stage: Phase III
