Zydus reported positive topline data from its Phase 2b/3 EPICS-III trial of saroglitazar in PBC 2 Line

Zydus Therapeutics reported positive topline results for the Phase 2b/3 EPICS-III trial (N=196; PCD: Apr 2025), evaluating the safety and efficacy of saroglitazar (PPAR α/γ agonist) for the treatment of PBC in adults with an inadequate response or intolerance to UDCA.

The Company reported that saroglitazar met its primary and secondary endpoints with a favorable safety profile and guided toward a US NDA submission in Q1 2026.

Key updates:

• Topline data:
  • Primary endpoint met: At Week 52, a placebo-adjusted 48.5% treatment difference in biochemical response was reported between the saroglitazar 1mg group vs placebo (p<0.001)
    • Biochemical response definition: ALP < 1.67x ULN, ≥15% ALP reduction from baseline, and total bilirubin ≤ 1x ULN
    • Only treatment difference was reported, not absolute results from the saroglitazar or placebo groups
  • Secondary endpoint met: The proportion of patients with complete ALP normalization (ALP ≤ 1x ULN) at 52 weeks was significantly higher in the saroglitazar group
    • Actual proportion of patients with ALP normalization not reported
  • Safety:
    • Zydus reported that saroglitazar 1 mg was generally well tolerated, with overall adverse events balanced between the 1 mg treatment group and placebo

• Zydus is targeting a US NDA submission in Q1 2026
  • The company emphasized that saroglitazar is the first PPAR α/γ agonist to show positive Phase 3 data in PBC, noting its potential to expand treatment options for patients with high unmet need who do not respond to standard therapy

Additional Insights:

• A US NDA submission for saroglitazar in Q1 2026 could place potential FDA approval as early as Q3 2026 with Priority Review or Q1 2027 with Standard Review
  • However, there is currently no ongoing or planned trial evaluating PBC outcomes for saroglitazar and it is unclear how US regulators will respond to the lack of such a trial considering that it was required for both Iqirvo and Livdelzi
  • If saroglitazar is approved in the US, it would become the third PPAR agonist available in 2L PBC, joining Ipsen’s Iqirvo and Gilead’s Livdelzi
• While full data has not been released, Zydus has reported a 48.5% treatment difference in biochemical response between saroglitazar and placebo which exceeds that of Livdelzi (42% placebo-adjusted difference) and Iqirvo (47% placebo-adjusted difference)
  • Notably multiple factors critical for full evaluation of saroglitazar’s efficacy results have not yet been reported including the absolute rates for biochemical response, ALP normalization rates, and the ALP thresholds defining 1x ULN
• The difference in biochemical response was numerically lower in EPICS-III (48.5% vs 61% in EPICS) compared to saroglitazar’s Phase 2 EPICS trial (N=37; PCD: Aug 2020), though the absence of absolute response rates limits direct comparison (comparison of known trial results listed in Table 1)
• Zydus has stated that full EPICS-III data will be presented at future scientific congress with AASLD 2025 (Nov 7–11, 2025) as the most likely option

Table 1: EPICS and EPICS-III trial data