Zydus Presents Saroglitazar Analysis from EPICS-III Trial at ACG 2026
New Delhi: Zydus Therapeutics Inc., a wholly owned subsidiary of Zydus Lifesciences Ltd., has presented new exploratory analyses from the pivotal EPICS-III Phase 2(b)/3 clinical trial evaluating saroglitazar in adults with primary biliary cholangitis (PBC) at the American College of Gastroenterology (ACG) 2026 Annual Meeting.
The late-breaking oral presentation, delivered by Raj Vuppalanchi, MD, Professor of Medicine at Indiana University School of Medicine and global principal investigator of the EPICS-III study, examined whether the treatment effects observed with saroglitazar were consistent across geographic regions, particularly between patients in the United States and those outside the country.
Saroglitazar remains an investigational drug and has not been approved by the US Food and Drug Administration (FDA). Its safety and effectiveness have not yet been established.
The post hoc exploratory analysis compared treatment outcomes among US and non-US participants enrolled in the EPICS-III trial. The US subgroup included 28 patients treated with saroglitazar and 14 receiving placebo, while the non-US subgroup comprised patients from Argentina, Iceland and Turkey, including 69 saroglitazar-treated patients and 37 placebo-treated patients.
Composite biochemical response rates were higher with saroglitazar than placebo in both subgroups. In the US population, the response rate was 60.7% with saroglitazar compared with 0% with placebo. In the non-US population, the corresponding rates were 55.1% and 13.5%, respectively.
The unstratified treatment difference was 60.7 percentage points in the US subgroup, compared with 41.6 percentage points in the non-US subgroup.
The analysis also evaluated alkaline phosphatase (ALP) normalization at Week 52, defined as an ALP level below 116 U/L. The treatment differences in ALP normalization were broadly comparable between the US and non-US subgroups, at 7.7 and 9.6 percentage points, respectively. One additional US participant in the saroglitazar group did not meet the normalization threshold but recorded an ALP level of 117 U/L at Week 52.
ALP levels also showed a numerically greater reduction from baseline among patients receiving saroglitazar in both geographic subgroups. In the US subgroup, the treatment difference in ALP change from baseline was −166.2 U/L, compared with −104.7 U/L in the non-US subgroup.
Saroglitazar was generally well tolerated in the EPICS-III study, with adverse events generally balanced between the treatment and placebo groups. The most common adverse reactions reported among patients receiving saroglitazar were pruritus, headache and urinary tract infection.
Commenting on the findings, Vuppalanchi said the analysis provided additional insight into the Phase 3 results and the biochemical responses observed across geographic regions.
He cautioned that the findings came from a post hoc analysis and should be interpreted accordingly, adding that continued evaluation of the EPICS-III data would help improve understanding of the results across the study population.
Zydus Therapeutics is developing saroglitazar for the treatment of PBC in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as a monotherapy for patients unable to tolerate the treatment.
The drug is currently under review by the US FDA. If approved, Zydus Therapeutics plans to launch saroglitazar in the US by March 2027.
Saroglitazar is a peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist being investigated for PBC. According to the company, its biological profile is intended to target bile acid toxicity and liver inflammation. The drug has received Orphan Drug Designation, Fast Track Designation and Priority Review from the FDA for the treatment of PBC.
Primary biliary cholangitis is a rare, progressive autoimmune disease that damages the bile ducts in the liver, leading to bile accumulation. Over time, the condition can cause liver fibrosis, cirrhosis, the need for liver transplantation or death.
The disease is associated with elevated biochemical markers, particularly ALP and bilirubin. Common symptoms include pruritus, or itching, and fatigue, which can significantly affect patients' quality of life.
EPICS-III is a multicentre, randomised, double-blind, placebo-controlled Phase 2(b)/3 trial evaluating the efficacy and safety of saroglitazar in patients with PBC who had an inadequate response to or intolerance of UDCA.
Following optimal dose selection, the Phase 3 portion of the study randomised 148 patients in a 2:1 ratio to receive saroglitazar magnesium 1 mg or placebo. The 1 mg formulation comprises 0.97 mg of saroglitazar and 0.03 mg of magnesium.
Zydus Therapeutics Inc., headquartered in Pennington, New Jersey, is a wholly owned subsidiary of Zydus Lifesciences Ltd. The specialty-focused biopharmaceutical company is developing treatments for rare and serious liver diseases, including PBC and metabolic dysfunction-associated steatohepatitis (MASH).
Zydus Lifesciences is a global life sciences company engaged in discovering, developing, manufacturing and marketing healthcare therapies. The group employs more than 30,000 people worldwide, including approximately 1,500 scientists working in research and development, and focuses on developing healthcare solutions across vaccines, therapeutics, biologicals and new chemical entities.
