Efficacy and safety of seladelpar in patients with primary biliary cholangitis and compensated liver cirrhosis in the open-label long-term ASSURE safety study: interim results

Document Type

Conference Proceeding

Publication Date

6-1-2024

Publication Title

J Hepatol

Abstract

Background and aims: Seladelpar, a potent and selective PPAR-delta agonist (ie, a delpar), has anti-cholestatic and anti-pruritic activity in patients with primary biliary cholangitis (PBC). The ongoing international, phase 3 ASSURE study (NCT03301506) is an openlabel long-term study of seladelpar in patients with PBC who participated in a prior seladelpar study. Here we report interim efficacy and safety results on a subset of patients with compensated liver cirrhosis. Method: Patients with PBC and cirrhosis were eligible for ASSURE if they had an inadequate response or intolerance to ursodeoxycholic acid (UDCA), previously participated in a seladelpar study, and had no history of hepatic decompensation. All patients received open-label seladelpar 10 mg oral daily. As of the data cutoff (29 June 2023), 174 patients from previous seladelpar studies (CB8025–21629 NCT02955602; CB8025-31731, NCT03301506; ENHANCE NCT03602560; CB8025-21838, NCT04950764) had enrolled, of whom 33 had compensated liver cirrhosis at study entry. Biochemical efficacy end points included the composite response of alkaline phosphatase (ALP) <1.67x upper limit of normal (ULN), ALP decrease ≥15%, and total bilirubin ≤ULN; ALP normalization; and change from baseline in ALP, total bilirubin, gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) all at Month 12. Results: Of the 33 patients with cirrhosis, most were female (91%) with a mean age of 60.4 years. Eight patients (24.2%) had portal hypertension, 93.9% were Child-Pugh (CP) class A, and 6.1% were CPB. Mean baseline liver stiffness by FibroScan was 19.3 kPa. At baseline mean ALP was 241.9 U L, and total bilirubin was 0.92 mg dL (27.3% >ULN). As of the data cutoff date, 23 patients with compensated cirrhosis had completed 12 months of treatment. Twelve out of 23 (52.2%) patients met the composite biochemical end point at Month 12. ALP normalization occurred in 39.1% (9 23 patients) at Month 12 and the mean percent change from baseline in ALP was −38.1% (absolute change: −99.5 U L). Reductions were also observed in GGT and ALT (percent changes from baseline: −35.1% and −19.6% respectively) at Month 12; no change was observed in AST or total bilirubin. There were no serious adverse events that were liverrelated or related to study drug and no discontinuations due to adverse events. Conclusion: In this interim analysis of the ongoing ASSURE study PBC patients with compensated cirrhosis treated with seladelpar 10 mg for 12 months achieved clinically meaningful improvements in markers of cholestasis and liver injury. Seladelpar appeared overall safe andwell tolerated. These findings suggest that seladelpar has the potential to offer a safe and effective therapy for PBC patients with compensated cirrhosis.

Volume

80

First Page

S20

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