Biochemical response is associated with liver stiffness stability in patients with primary biliary cholangitis treated with seladelpar for up to 36 months: interim results from the open-label ASSURE study

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Introduction: Liver stiffness measurement (LSM) is a non-invasive indicator associated with clinical outcomes in patients (pts) with liver disease, including primary biliary cholangitis (PBC). The ongoing, open-label Phase 3 ASSURE study (NCT03301506) evaluates long-term efficacy and safety of seladelpar (SEL). We reported stability of LSM in SEL treated pts with up to 3 years (yrs) of treatment in an interim ASSURE analysis. Objectives: Here, we report the association of biochemical response at Month (M) 12 with LSM change in ASSURE. Methodology: Pts from RESPONSE (NCT04620733) and legacy SEL studies enrolled in ASSURE, receiving open-label SEL 10 mg daily. LSM by FibroScan was an exploratory endpoint. Values with confirmed interquartile range (IQR)/LSM ratio>30% were excluded. We conducted an interim analysis of all pts in ASSURE with≥1 post-baseline (BL) LSM as of 31 Jan 2025. BL was defined as SEL initiation in RESPONSE or ASSURE. Composite biochemical response (CBR) at M12 was defined as alkaline phosphatase (ALP)<1.67×the upper limit of normal (ULN),≥15% ALP reduction from BL and total bilirubin≤ULN. LSM changes by CBR status at M12 were assessed through M36. LSM change>30% was considered clinically meaningful. Comparison of BL characteristics and multivariate analysis were performed to identify factors associated with stable/improved vs worsening LSM (>30%) at M36. Result: A total of 311 pts were evaluable; 114 had available M36 LSM values. Overall, 68% (213/311) achieved CBR at M12. In CBR pts at M12, BL mean age was 59 yrs, ALP 244 U/L, and LSM 8.9 kPa. In pts without CBR at M12, BL mean age was 57 yrs, ALP 384 U/L, and LSM 12.1 kPa. In CBR pts at M12, LSM remained stable (median change,−7%) at M36, vs LSM increase in pts without CBR at M12 (median change,+27% at M36). Among pts with vs without CBR at M12, 19% vs 9% improved LSM by>30% and 15% vs 48% worsened LSM by>30%. Pts who were stable/improved were older and had lower ALP (<1.5 x ULN, 19% vs 0%) at BL with higher rates of achieving CBR at M12 (87% vs 56%) compared to those who worsened (p<0.05). Multivariate analysis showed CBR at M12 was associated with stable/improved LSM at M36 (odds ratio 5.57; p<0.05). Conclusion: In ASSURE, biochemical response with SEL at M12 was related to liver stiffness stability up to 3 yrs. Further assessment of the impact of biochemical improvement on liver stiffness with SEL is warranted. Previous presentation: AASLD 2025. 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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