Saroglitazar Trial in PBC Patients with Incomplete Response to UDCA

On February 20^th, 2026, Zydus listed the Phase 3 EPICS-IV trial (N=89; SSD: Mar 2026; PCD: Jul 2028), which will assess the efficacy of saroglitazar (PPAR α/γ agonist) in PBC patients who have an incomplete response or are intolerant to UDCA.

• The double-blind, randomized trial will evaluate 1mg saroglitazar against a matched placebo
• Key trial details are as follows: 
  • Current status: “Not yet recruiting”
  • Estimated SSD: Mar 2026
  • Estimated PCD: Jul 2028
  • Estimated enrollment: 89 participants
• Key inclusion criteria
  • Adults between 18–80 years with confirmed PBC diagnosis, on stable UDCA for ≥6 months or UDCA-intolerant, with ALP > 1×ULN and < 1.67×ULN and TB ≤ 2×ULN at screening
• Key exclusion criteria
  • Patients with cirrhosis (Child-Pugh-Turcotte B/C or MELD-Na ≥12), decompensated liver disease, concomitant liver diseases, or use of OCA, fibrates, or other PPAR agonists within 12 weeks prior to screening
• Primary outcome is the incidence of participants achieving ALP ≤ 1xULN and ≥15% decrease from baseline in ALP, measured from baseline to Week 52
• Secondary outcomes are as follows: 
  • Incidence of participants achieving ALP ≤ 1xULN and ≥15% decrease from baseline in ALP, from baseline to Week 4
  • Change from baseline in the Global PBC Study Group (GLOBE) score from baseline to Week 52
  • Change from baseline in the United Kingdom Primary Biliary Cholangitis (UK-PBC) risk score from baseline to Week 52
• No trial sites have been listed yet

• The listing of this new EPICS-IV trial suggests Zydus plans to target PBC patients with incomplete response to UDCA (i.e., ALP = 1-1.67xULN) in addition to PBC patients with ALP > 1.67xULN studied in the phase 2b/3 EPICS III trial
• The EPICS-IV trial is broadly comparable to Gilead’s Phase 3 IDEAL trial (N=90; PCD: Jun 2026) and Ipsen’s Phase 3 ELSPIRE trial (N=69; PCD: Jun 2026) which are gathering data in a similar incomplete responders population for Livdelzi and Iqirvo respectively with key differences between the trials:
  • ELSPIRE‘s primary endpoint only evaluates ALP normalization, while IDEAL and EPICS-IV both evaluate a composite biochemical response measure as the primary endpoint
  • ELSPIRE will evaluate a broad range of patient-reported outcomes as secondary endpoints, while EPICS-IV currently lists limited secondary endpoints but includes PBC-prognostic scores such as GLOBE and UK-PBC
  • Gilead’s IDEAL trial and Ipsen’s ELSPIRE trial are significantly further ahead, with both trials expected to readout in H2 2026
• Zydus plans to file a NDA for saroglitazar in 2L in the US in Q1 2026 based on the pivotal Phase 2b/3 EPICS-III trial (N=196; PCD: Apr 2025), with the earliest approval expected in Q3/Q4 2026 if granted priority review
  • Preparations for the FDA filing are ongoing; to date, Zydus has not shared any ex-US filing plans for saroglitazar
  • While Zydus shared topline results in Aug 2025, full data from the pivotal Phase 2b/3 EPICS-III trial (N=196; PCD: Apr 2025) is still outstanding with Zydus management stating intentions to release data "in one of the major conferences...most probably in the May EASL [2026 conference]"
• Zydus is also expecting to initiate the Phase 4 EPICS-V trial (N=386; PCD: Nov 2032) in February 2026, its outcomes-based confirmatory trial, likely a regulatory requirement for the anticipated NDA filing of saroglitazar
  • Trial design for EPICS-V is in line with Gilead's AFFIRM (N=318; PCD: Aug 2030) and Ipsen's ELFIDENCE (N=276; PCD: May 2029) confirmatory trials