Saroglitazar

PBC slowly destroys the small bile ducts inside the liver, and the bile acids that back up damage liver cells over time. PPARs are a family of receptors that act as control switches for genes that handle fats, bile acids and inflammation. Saroglitazar switches on the alpha and gamma forms. The 2 PBC pills approved in 2024 also work on this family: elafibranor (Iqirvo) on the alpha, delta and gamma forms in lab tests, and seladelpar (Livdelzi) on the delta form.

In EPICS-III, saroglitazar lowered alkaline phosphatase (ALP), the liver blood test that rises when bile flow is blocked, by an average of 33.5% over a year, while it rose 6.5% on placebo, according to Zydus. A lower ALP has not yet been shown to mean a longer life or less liver failure on saroglitazar, which is what the EPICS-V outcome trial is measuring.

EPICS-III (NCT05133336) was a double-blind, placebo-controlled Phase 2b/3 trial in adults with PBC who had not responded well enough to UDCA or could not tolerate it^[5]. In its Phase 2b part, 37 people received placebo or saroglitazar magnesium 1mg or 2mg for 16 weeks. The Phase 3 part then randomized 148 people to the 1mg dose (97) or placebo (51) for 52 weeks.

The main goal was a combined lab response: ALP below 1.67 times the upper limit of normal, a drop in ALP of at least 15% and a normal bilirubin level. At week 52 that goal was reached by 56.7% on saroglitazar against 9.8% on placebo, and ALP came down to normal in 8.2% against 0%. Among people whose starting ALP was no more than 3 times normal, 79.0% responded against 14.3%.

The saroglitazar group started with higher ALP and other liver test values than the placebo group. Among people with marked itch at the start (a 5-D Itch score of 12 or more), itch improved 3.2 points more than on placebo at week 24, but that difference was not maintained at week 52^[2]. Results were published in Hepatology on October 26, 2026^[2].

An earlier Phase 2 proof-of-concept study (EPICS, NCT03112681) of 37 people found that saroglitazar 2mg and 4mg lowered ALP by 51% and 49% over 16 weeks, against 3% on placebo^[3].

Saroglitazar has no US label yet, so the warnings an FDA label would carry are not known. In the 52-week Phase 3 part of EPICS-III, adverse events of any kind occurred in 81.1% of people on saroglitazar against 90.5% on placebo, and serious adverse events in 6.3% against 11.1%^[2]. Zydus reports that most side effects were mild to moderate, that investigators judged none of the serious events to be caused by the study drug, and that no treatment-related deaths occurred.

Headache, high blood pressure, upper respiratory infections, abdominal pain, COVID-19, diarrhea and low vitamin D were each reported in more than 5% of people on saroglitazar and at least 2 percentage points more often than on placebo^[1]. In the earlier Phase 2 study, 4 people stopped saroglitazar because their liver enzymes (aminotransferases) rose, 3 of them on a 4mg dose, and the levels returned to baseline after stopping; the researchers moved to lower doses for that reason^[3].

Saroglitazar was developed by Zydus, then called Zydus Cadila, in India. The Drug Controller General of India approved it in June 2013 under the brand name Lipaglyn for diabetic dyslipidemia, abnormal blood fats in people with type 2 diabetes, according to a 2014 review in Current Drug Targets^[4]. Its first PBC study, a Phase 2 trial run at US centers, was published in the Journal of Hepatology in 2022^[3].

On May 28, 2026, Zydus announced that the FDA had accepted its new drug application for PBC with priority review and a target action date of November 27, 2026. The drug has Orphan Drug and Fast Track designations for PBC, and Zydus said it plans a US launch by March 2027 if it is approved^[1]. EPICS-III results were presented at the EASL Congress on May 30, 2026^[1] and published in Hepatology on October 26, 2026^[2].

A long-term outcome trial, EPICS-V (NCT07216235), began in March 2026 and is measuring liver decompensation, liver transplant, death and other signs of advancing liver disease over 4 years, with its primary completion planned for November 2032^[6]. A further Phase 3 trial, EPICS-IV (NCT07424677), and an open-label extension (NCT06427395) are also listed on ClinicalTrials.gov^[7][8]. The FDA had not announced a decision as of November 6, 2026.