Seladelpar is associated with a sustained reduction in cholestatic markers and a consistent safety profile in patients with primary biliary cholangitis treated up to 48 months in the ongoing, open-label ASSURE study

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Introduction: Seladelpar (SEL) is a first-in-class delpar (selective PPAR-delta agonist) indicated for primary biliary cholangitis (PBC) treatment in combination with ursodeoxycholic acid (UDCA) in adults with inadequate response to UDCA/as monotherapy in patients (pts) intolerant to UDCA. Objectives: We report the latest interim, long-term biochemical efficacy/safety data in a pooled population of pts treated with SEL in ASSURE. Methodology: The ASSURE study (NCT03301506) is an ongoing, open-label, long-term, Phase 3 trial of SEL in pts with PBC rolling over from the placebo-controlled, Phase 3 RESPONSE trial (NCT04620733) or with prior participation in legacy SEL trials. The Phase 2 and 3 parent studies for ASSURE required an inadequate response or intolerance to UDCA. Using a data cutoff of 31 Jan 2025, pts were pooled starting with initiation of SEL (at entry into RESPONSE for those randomised to SEL; at entry into ASSURE for all other pts). Pts received blinded, daily oral SEL 10 mg in RESPONSE and open-label, daily oral SEL 10 mg in ASSURE. Efficacy endpoints included a composite biochemical response (CBR; ALP<1.67×upper limit of normal [ULN], ALP decrease≥15% from baseline [BL], total bilirubin≤ULN), ALP normalisation, ALP% change from BL, and other laboratory parameters summarised through 36 months (M). Safety was assessed by exposure-adjusted adverse events (AEs) per 100 pt-yrs of exposure through 48M. Result: Among 337 pts treated with open-label SEL 10 mg, 258 were treated for≥2 yrs and 117 for≥3 yrs, with 122 pts reaching their 36M visit as of the data cutoff. At all time points, the majority of pts achieved a CBR: 69%(225/325) at 12M, 70%(181/258) at 24M, and 67%(82/122) at 36M ([ Fig. 1A ]). ALP normalised in 35% of pts (114/325) who reached their 12M visit, with similar percentages of 37%(96/258) at 24M and 34%(41/122) at 36M ([ Fig. 1B ]). Treatment with SEL resulted in sustained reductions in ALP, with mean% changes from BL of−43% at 12M,−43% at 24M, and−40% at 36M ([ Fig. 1C ]). Sustained reductions were also observed in ALT and GGT through 36M. SEL was well tolerated, with overall AEs reported in 83.2 pts per 100 pt-yrs in yr 1 and 62.3 in yr 4. Fig. 1 Conclusion: SEL led to sustained reductions in biochemical markers of cholestasis with up to 36M of open-label treatment. SEL appeared to be safe and well tolerated; no new safety signals were identified with up to 48M of follow-up. Previous submission: EASL 2026. Funding: Gilead Sciences, Inc. Publication History Article published online: 27 August 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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