Efficacy and safety of seladelpar in patients previously treated with fibrates or OCA

Document Type

Conference Proceeding

Publication Date

5-1-2025

Publication Title

J Hepatol

Abstract

Background and aims: Seladelpar is a first-in-class delpar (selective PPAR-delta agonist) indicated for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid (UDCA) in patients (pts) with an inadequate response to UDCA or as monotherapy in pts unable to tolerate UDCA. RESPONSE was a Phase 3, randomised, placebo-controlled clinical trial of seladelpar in pts with inadequate response intolerance to UDCA. Pts completing RESPONSE were eligible to roll over into ASSURE (NCT03301506), an ongoing, open-label, long-term, Phase 3 safety trial. Here we describe data from month 18 (month 6 of ASSURE) in pts with or without prior use of fibrates or obeticholic acid (OCA) who rolled over from RESPONSE into ASSURE. Method: Pts received 10 mg seladelpar orally daily or placebo in RESPONSE; pts received open-label 10 mg seladelpar in ASSURE. Fibrates and OCA were prohibited during the study period and a 6- week washout was required prior to entry in RESPONSE. Data are described for pts in ASSURE with or without prior use of fibrates OCA and based on whether they received seladelpar (continuous seladel par pts) or placebo (crossover pts) in RESPONSE. Efficacy included the percentage of pts achieving a composite biochemical response (CBR; alkaline phosphatase [ALP] <1.67 × upper limit of normal [ULN], ALP decrease ≥15%, and total bilirubin ≤ULN). Safety assessments included adverse events (AEs) and laboratory parameters. Results: Among pts who continued into ASSURE from RESPONSE (158), 16 continuous seladelpar and 11 crossover pts reported prior use of fibrates OCA (total, n = 27; 17%); 88 continuous seladelpar and 43 crossover pts reported no prior use of fibrates OCA (total, n = 131; 83%). At month 18, among continuous seladelpar pts, 9 15 (60%) pts with prior fibrate OCA use achieved a CBR vs 54 87 (62%) pts without prior fibrate OCA use. Among crossover pts, 7 11 (64%) pts with prior fibrate OCA use vs 32 41 (78%) pts without prior fibrate OCA use achieved a CBR at month 6 of ASSURE. From ASSURE initiation to month 6, incidence of AEs was similar across continuous seladelpar and crossover pts, regardless of prior OCA fibrate use; no treatment-related serious AEs were reported. Conclusion: In this interim analysis of continuous seladelpar and crossover pts from ASSURE, pts who reported prior use of fibrates OCA achieved a similar sustained biochemical response with seladelpar compared with pts who reported no prior use. Seladelpar appeared safe and well tolerated in this subgroup.

Volume

82

First Page

S309

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