Long-Term Efficacy and Safety of Open-Label Seladelpar Treatment in Patients With Primary Biliary Cholangitis: Pooled Interim Results for up to 3 Years From the ASSURE Study

Document Type

Conference Proceeding

Publication Date

2-1-2025

Publication Title

Dig Liver Dis

Keywords

placebo, seladelpar, ursodeoxycholic acid, adult, adverse drug reaction, biliary cirrhosis, conference abstract, controlled study, drug therapy, female, human, major clinical study, male, middle aged, numeric rating scale, phase 3 clinical trial, primary biliary cirrhosis, pruritus, side effect, therapy

Abstract

Introduction: ASSURE (NCT03301506) is an ongoing, open-label, long-term, Phase 3 trial of seladelpar—a novel delpar (selective PPARδ agonist)—in patients (pts) with primary biliary cholangitis who rolled over from the Phase 3, placebo-controlled RESPONSE trial (NCT04620733) and from legacy trials (ENHANCE [NCT03602560], CB8025-21629 [NCT02955602], CB8025-31731 [NCT03301506], CB8025-21838 [NCT04950764]). Eligibility criteria included inadequate response or intolerance to ursodeoxycholic acid. Aim: To present pooled interim efficacy and safety results from the RESPONSE trial and from legacy trials. Materials and Methods: Data cutoff: January 31, 2024. Patient exposure to seladelpar in ASSURE was analyzed. Key efficacy endpoints included composite biochemical response (CBR; ALP <1.67 × ULN, ALP decrease ≥15%, TB ≤ULN) and ALP normalization. Pruritus was assessed using a numeric rating scale (NRS; 0–10) through month (M) 6; change from baseline (BL) was assessed at M6 in pts with moderate-to-severe pruritus (NRS ≥4). Adjusted adverse events (AEs) were calculated per 100 pt-years. Baseline included first exposure to seladelpar in ASSURE or RESPONSE. Results: 337 pts received 10 mg of seladelpar daily. At BL, mean age was 58.1 (9.7) years, 94% were female, mean ALP was 287.5 (128.4) U/L, TB was 0.75 (0.34) mg/dL, and 16% had cirrhosis. At M12, M24, and M30, 204/280 (73%), 90/124 (73%), and 30/37 (81%) achieved the CBR endpoint, respectively, with ALP normalization in 38%, 38%, and 41%. Mean NRS pruritus change at M6 was −3.3 (SE 0.24) among 99 pts. Exposure-adjusted AEs occurred in 86, 70, and 63 pts per 100 pt-years by M12, M24, and M36, respectively. No serious treatment-related AEs were reported. Conclusions: Seladelpar showed durable biochemical response by M30, with 81% achieving CBR, 41% attaining ALP normalization, and robust pruritus improvement. It remained safe and well tolerated, showing consistent safety over 3 years.

Volume

57

First Page

S88

Last Page

S89

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