Zydus Therapeutics, the US-based specialty arm of Zydus Lifesciences, has announced positive topline results from the pivotal EPICS-III Phase 2b/3 clinical trial evaluating Saroglitazar in adult patients with Primary Biliary Cholangitis (PBC). The company plans to submit a US regulatory application for the investigational drug in the first quarter of 2026.
Trial Design and Patient Population
The EPICS-III study evaluated the safety and efficacy of Saroglitazar, an investigational alpha/gamma Peroxisome Proliferator-Activated Receptor (PPAR) agonist, in adult patients with PBC who had an inadequate response or intolerance to ursodeoxycholic acid (UDCA), the current standard of care.
Primary Endpoint Achievement
The trial met its primary composite endpoint with a statistically significant treatment difference. Saroglitazar 1 mg achieved a biochemical response rate with a treatment difference of 48.5% compared to placebo (P<0.001). The biochemical response was defined as alkaline phosphatase (ALP) less than 1.67 times the upper limit of normal (ULN), a ≥15% decrease of ALP relative to baseline, and total bilirubin ≤ ULN or direct bilirubin ≤ ULN in patients with known Gilbert's syndrome at 52 weeks.
Secondary Endpoint Results
The trial also met its key secondary endpoint, demonstrating the proportion of subjects with complete normalization of ALP, defined as ALP ≤ ULN at 52 weeks. ALP and bilirubin serve as important predictors of PBC disease progression.
Safety Profile
Saroglitazar 1 mg was generally well tolerated throughout the 52-week study period. Overall adverse events were generally balanced between Saroglitazar-treated and placebo-treated patients, indicating a favorable safety profile for this patient population.
Clinical Significance and Expert Commentary
Pankaj Patel, Chairman of Zydus Lifesciences, emphasized the clinical importance of these results: "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."
Raj Vuppalanchi, Professor of Medicine at Indiana University School of Medicine and Global Principal Investigator for the EPICS-III study, highlighted the clinical need: "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."
Drug Mechanism and Disease Context
Saroglitazar is a novel PPAR alpha/gamma agonist with a distinct biological profile that targets both bile acid toxicity and liver inflammation. Primary Biliary Cholangitis is a rare, progressive autoimmune disease that gradually destroys bile ducts, resulting in bile accumulation in the liver. This can lead to fibrosis, cirrhosis, the need for liver transplantation, or death. PBC is characterized by increases in biochemical markers, especially ALP and bilirubin, with clinical symptoms including pruritus and fatigue.
Regulatory Timeline
Zydus Therapeutics intends to discuss these results with regulatory agencies and move forward with a regulatory submission to the US Food and Drug Administration in the first quarter of 2026. The full data from the EPICS-III trial will be presented at a future scientific congress.
