Zydus Therapeutics Receives FDA Priority Review for Saroglitazar in Primary Biliary Cholangitis
Key Insights
The US FDA (search) granted Priority Review to Zydus Therapeutics (search)' New Drug Application for saroglitazar to treat primary biliary cholangitis (search), with a target action date of November 27, 2026.
The EPICS-III Phase 3 trial demonstrated that 56.7% of patients achieved biochemical response with saroglitazar versus 9.8% with placebo, representing a 48% treatment difference.
Saroglitazar significantly reduced alkaline phosphatase levels by 33.5% compared to a 6.5% increase in the placebo group, addressing a key surrogate marker for long-term outcomes.
Zydus Therapeutics (search) announced that the US Food and Drug Administration has granted Priority Review to its New Drug Application for saroglitazar, a novel PPAR α/γ (search) agonist for treating primary biliary cholangitis (search) (PBC (search)). The FDA assigned a Prescription Drug User Fee Act target action date of November 27, 2026, for the proposed indication of treating PBC in combination with ursodeoxycholic acid in adults with inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA.
Phase 3 Trial Results Demonstrate Significant Efficacy
The NDA is supported by results from the EPICS-III trial, a randomized, double-blind, placebo-controlled Phase 3 study that enrolled 148 patients with PBC (search) who had inadequate response to or intolerance of ursodeoxycholic acid. The trial met its primary endpoint at Week 52, demonstrating statistically significant improvement in biochemical response compared to placebo.
"EPICS-III is a registrational study that tested saroglitazar as a second-line treatment in patients with PBC (search). The study met its primary endpoint, demonstrating a clinically meaningful biochemical response, along with a favorable safety and tolerability profile," said Dr. Raj Vuppalanchi, Professor of Medicine at Indiana University School of Medicine and Global Principal Investigator for the EPICS-III study.
A total of 56.7% of patients treated with saroglitazar achieved biochemical response compared with 9.8% of patients receiving placebo, representing a treatment difference of 48% (95% CI: 35.3, 60.8) (p < 0.001). Among participants with baseline alkaline phosphatase ≤ 3 x upper limit of normal, biochemical response rates were 83.1% and 14.7%, respectively.
Substantial Reduction in Key Biomarker
Patients receiving saroglitazar demonstrated significant improvements in alkaline phosphatase (ALP) levels, a critical surrogate marker for long-term outcomes in PBC (search). At Week 52, saroglitazar showed a treatment difference of -124.1 U/L (-40.1%) in least-squares mean change from baseline in ALP. Patients receiving saroglitazar achieved a -115.4 U/L (-33.5%) reduction from baseline compared with a +8.8 U/L (+6.5%) increase from baseline among patients receiving placebo.
"The magnitude of separation between saroglitazar and placebo in biochemical response is a clinically meaningful result for patients whose disease continues to progress on UDCA," said Dr. Kris Kowdley, Director of Liver Institute Northwest and Professor at Elson S. Floyd College of Medicine, Washington State University. "Achieving meaningful reductions in ALP is an important treatment goal in PBC (search) as it is a surrogate marker predictive of long-term outcomes."
Secondary Endpoints and Safety Profile
As a secondary endpoint, patients treated with saroglitazar experienced statistically significant reduction in pruritus at Week 24 compared to placebo, with a change from baseline in 5-D Itch Total score of -5.9 versus -2.7, representing a treatment difference of -3.2 (95% CI: -5.66, -0.82) (p = 0.009). However, at Week 52, the difference was not statistically significant.
Saroglitazar demonstrated a favorable safety profile in the EPICS-III trial. Most treatment-emergent adverse events were mild to moderate in nature. Serious adverse events occurred in 6.3% of patients in the saroglitazar group versus 11.1% in the placebo group, with none considered related to study treatment and no treatment-related deaths reported.
Addressing Unmet Medical Need
Primary biliary cholangitis (search) is a rare, progressive autoimmune disease that gradually destroys bile ducts, resulting in bile accumulation in the liver and potentially leading to fibrosis, cirrhosis, liver transplantation, or death. The disease is characterized by increases in biochemical markers, particularly ALP and bilirubin, with clinical symptoms including severe pruritus and fatigue.
"The acceptance of our NDA with Priority Review highlights the significant unmet need that exists for patients with PBC (search) and represents an important step in the path to making saroglitazar available in the US," said Dr. Sharvil Patel, Managing Director of Zydus Lifesciences.
Saroglitazar has received multiple FDA designations including Orphan Drug Designation, Fast Track Designation, and Priority Review for PBC (search) treatment, reflecting its potential to address significant unmet needs in patients who do not adequately respond to current therapies. If approved, Zydus Therapeutics (search) plans to launch saroglitazar in the United States by March 2027.