Long-term efficacy and safety of open-label seladelpar in primary biliary cholangitis: pooled interim results up to 3 years from ASSURE

Document Type

Conference Proceeding

Publication Date

6-23-2025

Publication Title

Gut

Keywords

Gastroenterology & Hepatology

Abstract

Introduction: ASSURE (NCT03301506) is an ongoing, open-label, long-term, Phase 3 trial of seladelpar—a first-in-class delpar (selective PPAR-delta agonist)—in patients (pts) with primary biliary cholangitis (who had an inadequate response or intolerance to first-line ursodeoxycholic acid) rolling over from the Phase 3, placebo-controlled, registrational RESPONSE trial (NCT04620733) or with prior participation in legacy trials (Phase 3 ENHANCE [NCT03602560], CB8025-21629 [NCT02955602], CB8025-31731 [NCT03301506], CB8025-21838 [NCT04950764]). Here, we report pooled interim efficacy and safety for all pts in ASSURE. Methods: Using a data cutoff of 31 January 2024, pt exposure to seladelpar in ASSURE (including exposure in pts who were randomised to the active treatment arm in RESPONSE) was analysed. Key efficacy endpoints included composite biochemical response (CBR; alkaline phosphatase [ALP] <1.67× upper limit of normal [ULN], ALP decrease ≥ 15%, and total bilirubin [TB] ≤ ULN) and ALP normalisation. Pruritus was recorded using a numeric rating scale (NRS; 0–10) collected daily through month (M) 6; change from baseline (BL) was assessed through M6 in pts with moderate-to-severe pruritus (NRS ≥ 4) at BL. Exposure-adjusted adverse events (AEs) were calculated for each year on study as incidence per 100 pt-years. BL was based on first exposure to seladelpar in ASSURE or RESPONSE. Results: 337 pts received 10-mg seladelpar daily. 34 pts reached 30M on study; 90 pts had ≥ 24M of seladelpar exposure. At BL, the mean (SD) age was 58.1 (9.7) years, 318/337 (94%) pts were female, mean (SD) ALP was 287.5 (128.4) U/L, mean (SD) TB was 0.75 (0.34) mg/dL, and 55/337 (16%) had cirrhosis. At M12, M24, and M30, 204/280 evaluable pts (73%), 90/124 (73%), and 30/37 (81%) met the CBR endpoint, respectively (figure 1), and ALP normalised in 106/280 (38%), 47/124 (38%), and 15/37 (41%) pts, respectively. In the pruritus NRS, mean (SE) change from BL at 6M was −3.3 (0.24) among 99 evaluable pts. Exposure-adjusted AEs were observed in 86, 70, and 63 pts per 100 pt-years at M12, M24, and M36, respectively. There were no treatment-related serious AEs. Conclusions: By M30 of the long-term ASSURE study, seladelpar resulted in a durable and sustained biochemical response in 81% of pts, with an ALP normalisation rate of 41%, and robust improvement in pruritus. Seladelpar continues to appear safe and well tolerated, with no new safety signals or change in frequency of AEs with up to 3 years of exposure.

Volume

74

Issue

SUPPL_1

First Page

A205

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