Clinical Trial Results Analysis

Zydus Therapeutics Inc., a wholly owned subsidiary of Zydus Lifesciences Limited, presented new analyses from the pivotal EPICS-III Phase 2(b)/3 clinical trial of saroglitazar in adult patients with primary biliary cholangitis (PBC) at the American College of Gastroenterology (ACG) 2026 Annual Meeting.

Geographic Subgroup Analysis Results

The post hoc exploratory analysis investigated treatment effects across geographic regions, specifically comparing U.S. versus non-U.S. patients:

U.S. Population:

  • 28 patients treated with saroglitazar vs 14 placebo-treated patients
  • Composite biochemical response rates: 60.7% with saroglitazar vs 0% with placebo
  • Treatment difference (∆): 60.7%
  • ALP change from baseline at Week 52: -104 U/L with saroglitazar vs 62.2 U/L with placebo
  • Treatment difference in ALP change: ∆ -166.2 U/L

Non-U.S. Population (Argentina, Iceland, Turkey):

  • 69 patients treated with saroglitazar vs 37 patients treated with placebo
  • Composite biochemical response rates: 55.1% with saroglitazar vs 13.5% with placebo
  • Treatment difference (∆): 41.6%
  • ALP change from baseline at Week 52: -110.9 U/L with saroglitazar vs -6.2 U/L with placebo
  • Treatment difference in ALP change: ∆ -104.7 U/L

ALP Normalization Data

ALP normalization treatment difference rates at Week 52 were not substantially different between the U.S. and non-U.S. subgroups (7.7% vs. 9.6%). ALP normalization was defined as ALP<116 U/L.

Additional Observations:

  • One additional U.S. participant in the saroglitazar group had ALP value of 117 U/L at Week 52 (did not achieve normalization)
  • Three additional non-U.S. participants in the saroglitazar group had ALP values of 118, 119, and 120 U/L at Week 52 (did not achieve normalization)

Safety Profile

In EPICS-III, saroglitazar was generally well tolerated:

  • Adverse events generally balanced between saroglitazar-treated and placebo-treated patients
  • Most common adverse reactions in saroglitazar-treated patients: pruritus, headache, and urinary tract infection

Regulatory Status and Development

Saroglitazar is an investigational product that has not been approved by the U.S. Food and Drug Administration (FDA); its safety and effectiveness have not been established.

Current Status:

  • Under review by the FDA for treatment of PBC
  • Received Orphan Drug Designation, Fast Track Designation, and Priority Review from FDA
  • Planned US launch by March 2027 if approved

Intended Use:

  • Treatment of PBC in combination with UDCA in adults who have had an inadequate response to UDCA
  • As monotherapy in patients unable to tolerate UDCA

Trial Design Details

EPICS-III is a multicenter, randomized, double-blind, placebo-controlled, seamless Phase 2(b)/3 trial evaluating efficacy and safety of saroglitazar in patients with PBC who had inadequate response to or intolerance of UDCA.

Trial Parameters:

  • Phase 3 trial randomized 148 patients in 2:1 ratio
  • Dosage: saroglitazar magnesium 1 mg (equivalent to 0.97 mg saroglitazar and 0.03 mg magnesium) or placebo
  • Nearly thirty percent of patients were from the U.S.

Compound Information

Saroglitazar is a novel Peroxisome Proliferator-Activated Receptor (PPAR) α/γ agonist with distinct biological profile that targets both bile acid toxicity and liver inflammation.

Company Background

Zydus Therapeutics is a clinical-stage, specialty-focused biopharmaceutical company dedicated to developing transformative treatments for rare and serious liver diseases, including PBC and Metabolic Dysfunction-Associated Steatohepatitis (MASH). The company is headquartered in Pennington, New Jersey.

Zydus Lifesciences Ltd. employs over 30,000 people worldwide, including 1,500 scientists engaged in R&D.

Definitions

Composite biochemical response: Defined as achieving the following at Week 52: ALP < 1.67 x ULN, ≥ 15% decrease in ALP from baseline, and total bilirubin ≤ ULN or direct bilirubin ≤ ULN in subjects with known Gilbert's syndrome.

PBC: Primary biliary cholangitis is a rare, progressive autoimmune disease that gradually destroys the bile ducts, resulting in accumulation of bile in the liver, which can result in fibrosis, cirrhosis, need for liver transplantation, or death.