Zydus Therapeutics announces positive topline results from EPICS-III Phase 2b/3 trial of Saroglitazar in Primary Biliary Cholangitis

Zydus Therapeutics, a wholly owned subsidiary of Zydus Lifesciences, announced positive topline results from the pivotal EPICS-III Phase 2(b)/3 clinical trial. The study evaluated the safety and efficacy of Saroglitazar, an investigational alpha/gamma Peroxisome Proliferator-Activated Receptor (PPAR) agonist, in the treatment of adult patients with Primary Biliary Cholangitis (PBC) who had an inadequate response or intolerance to ursodeoxycholic acid (UDCA), the current standard of care.

The trial met its primary endpoint, with a statistically significant treatment difference in the percentage of patients achieving a clinically meaningful biochemical response with Saroglitazar compared to placebo. Saroglitazar was generally well tolerated, with overall adverse events generally balanced between Saroglitazar-treated and placebo-treated patients.

Zydus Therapeutics, the US-based specialty arm of Zydus Lifesciences, intends to submit a U.S. regulatory application for Saroglitazar in the first quarter of 2026.

The trial achieved its primary composite endpoint, with a treatment difference in achieving a biochemical response of 48.5 per cent, favouring Saroglitazar 1 mg compared to placebo (P<0.001). Biochemical response was defined as alkaline phosphatase (ALP) less than 1.67 times the upper limit of normal (ULN), a ≥15 per cent decrease of ALP relative to baseline, and total bilirubin ≤ ULN or direct bilirubin ≤ ULN in patients with known Gilbert’s syndrome at 52 weeks. ALP and bilirubin are important predictors of PBC disease progression.

The trial also met its key secondary endpoint, the proportion of subjects with complete normalisation of ALP, defined as ALP ≤ ULN at 52 weeks. Saroglitazar 1 mg was generally well tolerated, with adverse events generally balanced between Saroglitazar 1 mg-treated and placebo-treated patients.

Speaking on the development, Chairman of Zydus Lifesciences, Pankaj Patel, said,
“The EPICS-III results reinforce our commitment to advancing novel treatments for chronic liver disease — an area of high unmet medical need and growing global impact. Saroglitazar is the first PPAR alpha/gamma agonist to demonstrate positive Phase 3 data in patients with PBC and has the potential to bring real value to both patients and their healthcare providers who may need more options. As we look ahead, we’re excited about the potential of this investigational treatment and intend to discuss these results with regulatory agencies and plan to move forward with a regulatory submission to the U.S. Food and Drug Administration in the first quarter of 2026.”

Commenting on the trial, Raj Vuppalanchi, MD, Professor of Medicine at Indiana University School of Medicine and Global Principal Investigator for the EPICS-III study, said:
“In clinical practice, we often see patients who continue to struggle despite being on standard therapy. Expanding our treatment options with new therapies could significantly change how we personalise care for individuals with PBC who haven’t responded to first-line treatment. We are thankful to the patients, their families, and the investigators whose participation made this study possible.”

The full data from the EPICS-III trial will be presented at a future scientific congress.

About Primary Biliary Cholangitis (PBC):
Primary Biliary Cholangitis is a rare, progressive autoimmune disease which gradually destroys the bile ducts, resulting in accumulation of bile in the liver. This can lead to fibrosis, cirrhosis, the need for liver transplantation or death. PBC is characterised by increases in biochemical markers, especially ALP and bilirubin. Clinical symptoms include pruritus (itching) and fatigue.

About the EPICS-III Trial:
EPICS-III (NCT05133336) is a multicentre, randomised, double-blind, placebo-controlled, seamless Phase 2b/3 trial evaluating the efficacy and safety of Saroglitazar in patients with PBC who were resistant or intolerant to UDCA. After optimal dose selection, the Phase 3 trial randomised 149 patients in a 2:1 ratio of Saroglitazar 1 mg or placebo.