FDA Grants Priority Review to Saroglitazar NDA for Primary Biliary Cholangitis

The US Food and Drug Administration (FDA) has granted Priority Review to the new drug application (NDA) for saroglitazar in adults with primary biliary cholangitis (PBC).1

Announced on May 28, 2026, by parent company Zydus Therapeutics, the application seeks approval for use with ursodeoxycholic acid (UDCA) in adults with inadequate response to UDCA, or as monotherapy in those unable to tolerate UDCA. The FDA has also assigned a Prescription Drug User Fee Act target action date of November 27, 2026. Zydus said it plans a US launch by March 2027 if the agent is approved.1

“The acceptance of our NDA with Priority Review highlights the significant unmet need that exists for patients with PBC and represents an important step in the path to making saroglitazar available in the US,” Sharvil Patel, MD, managing director of Zydus Lifesciences, said in a statement. “We look forward to collaborating with the US FDA during the NDA Priority Review process and will, in parallel, continue to build our medical affairs and commercialization capabilities towards a potential US launch by March 2027.”1

Saroglitazar in PBC

Priority Review is reserved for applications involving drugs the FDA determines may offer meaningful improvements in safety or effectiveness for serious conditions. Saroglitazar also previously received Orphan Drug Designation and Fast Track Designation for PBC, according to Zydus.1

PBC is a chronic autoimmune cholestatic liver disease characterized by progressive bile duct injury and elevations in biochemical markers including alkaline phosphatase (ALP) and bilirubin. Guideline documents identify UDCA as first-line therapy, with biochemical response used to assess prognosis and need for additional treatment approaches in patients with inadequate response or intolerance. The proposed saroglitazar indication aligns with this second-line setting rather than treatment-naive disease.2,3

Saroglitazar is a peroxisome proliferator-activated receptor α/γ agonist; this mechanism places it within a broader therapeutic strategy aimed at modifying cholestatic and metabolic pathways, although the clinical relevance of receptor activity in PBC depends on trial outcomes rather than mechanism alone.1

EPICS-III Phase 3 Results

The NDA is supported by EPICS-III, a multicenter, randomized, double-blind, placebo-controlled seamless phase 2b/3 trial enrolling adults with PBC and inadequate response to or intolerance of UDCA. After dose selection, the phase 3 portion randomized 148 patients in a 2:1 ratio to saroglitazar magnesium 1 mg or placebo.1

At week 52, 56.7% of patients receiving saroglitazar achieved the primary endpoint of biochemical response compared with 9.8% receiving placebo, for a treatment difference of 48 percentage points (95% CI, 35.3-60.8; P < .001). The composite biochemical response endpoint required ALP less than 1.67 times the upper limit of normal, at least a 15% decrease in ALP from baseline, and total bilirubin at or below the upper limit of normal, with direct bilirubin criteria applied for patients with known Gilbert syndrome.1

Zydus also reported ALP changes favoring saroglitazar. Mean baseline ALP was 363 U/L in the saroglitazar group and 317.2 U/L in the placebo group. At week 52, least-squares mean change from baseline showed a treatment difference of −124.1 U/L, or −40.1%. Patients treated with saroglitazar had a 33.5% ALP reduction from baseline, while placebo recipients had a 6.5% increase.1

Safety Findings and Remaining Questions

In EPICS-III, pruritus was assessed as a secondary endpoint using the 5-D Itch Total score. At week 24, saroglitazar was associated with a statistically significant reduction versus placebo, with a change from baseline of −5.9 compared with −2.7, for a treatment difference of −3.2 (95% CI, −5.66 to −0.82; P = .009). At week 52, changes were −4.6 with saroglitazar and −4.4 with placebo, which was not statistically significant.1

The company reported saroglitazar was generally well tolerated. Most treatment-emergent adverse events were mild to moderate. Serious adverse events occurred in 6.3% of saroglitazar-treated patients and 11.1% of placebo-treated patients; investigators did not consider any serious adverse events related to study treatment, and no treatment-related deaths were reported. Treatment-emergent adverse events occurring in more than 5% of patients and at least 2 percentage points more often with saroglitazar included headache, hypertension, upper respiratory tract infection, abdominal pain, COVID-19, diarrhea, and vitamin D deficiency.1

The phase 3 data are scheduled for late-breaking presentation at the European Association for the Study of the Liver Congress in Barcelona, Spain, on May 30, 2026.1

“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,” Kris Kowdley, director of the Liver Institute Northwest, professor at the Elson S. Floyd College of Medicine, and senior scientific advisor and medical director at Velocity Clinical Research, said in a statement. “Achieving meaningful reductions in ALP is an important treatment goal in PBC as it is a surrogate marker predictive of long-term outcomes. These results suggest saroglitazar may provide a promising therapeutic option for patients with a suboptimal response to UDCA alone, when ALP continues to rise above target.”1

References

1. Zydus Therapeutics. Zydus Therapeutics New Drug Application (NDA) for Saroglitazar to Treat Primary Biliary Cholangitis (PBC) Granted Priority Review by the US FDA. PR Newswire. May 28, 2026. https://www.prnewswire.com/news-releases/zydus-therapeutics-new-drug-application-nda-for-saroglitazar-to-treat-primary-biliary-cholangitis-pbc-granted-priority-review-by-the-us-fda-302784488.html

2. Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419. doi:10.1002/hep.30145

3. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017;67(1):145-172. doi:10.1016/j.jhep.2017.03.022