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

We report interim efficacy/safety in a subset of patients with compensated liver cirrhosis (CC) from the open-label, long-term, phase 3 ASSURE study (NCT03301506) of seladelpar in primary biliary cholangitis (PBC). Patients with an inadequate response or intolerance to ursodeoxycholic acid, participation in a prior seladelpar study (NCT02955602, NCT03301506, NCT03602560, NCT04950764), and no history of hepatic decompensation were eligible. All received seladelpar 10 mg orally daily. As of June 29, 2023 (data cutoff), 174 patients enrolled; 33 had CC at study entry. Efficacy endpoints included the composite biochemical response (ALP<1.67×ULN, ALP decrease≥15%, and total bilirubin (TB)≤ULN), ALP normalization, and change from baseline (CFB) in ALP, total bilirubin, GGT, ALT, and AST at Month (M) 12. Of 33 patients with CC, most were female (91%), and mean age was 60.4 years. Eight patients (24.2%) had portal hypertension, 93.9% were Child-Pugh-A, and 6.1% were Child-Pugh-B. At baseline, mean liver stiffness was 19.3 kPa, mean ALP was 241.9 U/L, and TB was 0.92 mg/dL (27.3%>ULN). At data cutoff, 23 patients with CC completed 12M; 52.2% met the composite endpoint, and ALP normalized in 39.1%. Mean percent CFB at M12 in ALP, GGT, and ALT was−38.1%,−35.1%, and−19.6%, respectively; no changes occurred in AST or TB. No serious adverse events were liver or seladelpar related, and no discontinuations were due to adverse events. Seladelpar demonstrated clinically meaningful improvements in markers of cholestasis and liver injury and a tolerable safety profile in patients with PBC and CC.

Publication History

Article published online:
20 January 2025