Zydus Therapeutics Inc, a wholly owned subsidiary of Zydus Lifesciences Limited, has presented new findings from its EPICS-III clinical trial of saroglitazar in adults with primary biliary cholangitis (PBC). The post hoc exploratory analysis was presented by Raj Vuppalanchi, Professor of Medicine at Indiana University School of Medicine and Global Principal Investigator of the study, at the American College of Gastroenterology (ACG) 2026 Annual Meeting.
The analysis examined whether the biochemical responses observed with saroglitazar were consistent across geographic regions, with a particular focus on patients in the United States and those enrolled outside the country.In the U.S. subgroup, 28 patients received saroglitazar and 14 received placebo. The non-US group included 69 patients treated with saroglitazar and 37 who received placebo. The non-US participants were enrolled in Argentina, Iceland and Turkey.
Composite biochemical response rates at Week 52 were 60.7% among US patients receiving saroglitazar, compared with 0% in the placebo group. In the non-US subgroup, the corresponding rates were 55.1% and 13.5%. The treatment difference was 60.7 percentage points in the U.S. group and 41.6 percentage points in the non-US group.
The analysis also assessed alkaline phosphatase (ALP), a biochemical marker associated with PBC. Treatment differences in ALP normalization at Week 52 were broadly similar between the US and non-US subgroups, at 7.7 and 9.6 percentage points, respectively. ALP reductions from baseline were numerically greater with saroglitazar in both groups. In the US subgroup, the treatment difference was -166.2 U/L, while the non-U subgroup recorded a difference of -104.7 U/L.
“These findings provide additional insight into the Phase 3 EPICS-III results and the biochemical responses observed among patients enrolled in different geographic regions,” Mr Vuppalanchi said. He added that the findings should be interpreted in the context of the post hoc nature of the analysis.
In the EPICS-III trial, saroglitazar was generally well tolerated, with adverse events broadly balanced between treatment and placebo groups. The most common adverse reactions among patients receiving saroglitazar were itching, headache and urinary tract infection.
Saroglitazar is being developed for adults with PBC who have had an inadequate response to ursodeoxycholic acid (UDCA), or as a standalone treatment for patients unable to tolerate UDCA. The investigational drug is currently under review by the U.S. Food and Drug Administration (FDA). Zydus has said it plans to launch the treatment in the United States by March 2027, subject to approval.
PBC is a rare, progressive autoimmune disease that damages the bile ducts and can lead to liver damage, cirrhosis, liver transplantation or death. EPICS-III is a multicentre, randomized, double-blind, placebo-controlled trial evaluating saroglitazar in patients who did not respond adequately to, or could not tolerate, UDCA. Following dose selection, 148 patients entered the Phase 3 study and were assigned in a 2:1 ratio to saroglitazar magnesium 1 mg or placebo.
Saroglitazar is an investigational PPAR α/γ agonist that has received Orphan Drug Designation, Fast Track Designation and Priority Review from the FDA for PBC. Its safety and effectiveness have not been established, and it has not been approved by the FDA.
Zydus Therapeutics is a clinical-stage biopharmaceutical company focused on developing treatments for rare and serious liver diseases, including PBC and metabolic dysfunction-associated steatohepatitis. It is headquartered in Pennington, New Jersey, and is a wholly owned subsidiary of Zydus Lifesciences Limited.
