Safety of Seladelpar in Primary Biliary Cholangitis Patients with Cirrhosis and Clinical Signs of Portal Hypertension: Data from the Enhance and Response Studies

Document Type

Conference Proceeding

Publication Date

1-26-2026

Publication Title

Jahrestagung der Deutschen Arbeitsgemeinschaft zum Studium der Leber

Keywords

albumin, alkaline phosphatase, bilirubin, placebo, seladelpar, ursodeoxycholic acid, adult, ascites, biliary cirrhosis, conference abstract, controlled study, drug therapy, female, fibrosis, human, human tissue, liver biopsy, liver stiffness, male, medical history, portal hypertension, primary biliary cirrhosis, randomized controlled trial, second-line treatment, side effect, thrombocytopenia, transient elastography, varicosis

Abstract

Seladelpar is a first-in-class delpar (selective PPAR-delta agonist) approved for second-line treatment of primary biliary cholangitis (PBC) with ursodeoxycholic acid (UDCA). We present pooled safety data from ENHANCE (NCT03602560) and RESPONSE (NCT04620733) in a patient subgroup with cirrhosis and clinical signs of portal hypertension (PHT). Patients with PBC on UDCA for ≥ 12 months or who were UDCA intolerant, with alkaline phosphatase ≥ 1.67 × ULN and total bilirubin ≤ 2 × ULN, were randomised to placebo or seladelpar. Cirrhosis was defined by medical history, liver biopsy, transient elastography, laboratory findings, radiological features, or investigator’s clinical determination; signs of PHT were defined by thrombocytopenia, low albumin, elevated total bilirubin, or history of varices/ascites. 56 patients had cirrhosis at baseline across both studies; 27 had signs of PHT (21 seladelpar [15/21 on 10 mg]; 6 placebo). Mean (SD) liver stiffness was 17.4 (3.5) kPa with placebo and 21.0 (11.8) kPa with seladelpar. Overall, 5/6 (83 %) placebo and 15/21 (71 %) seladelpar patients experienced an adverse event (AE), and 2/6 (33 %) and 1/21 (5 %) discontinued treatment due to AEs. Serious AEs unrelated to treatment occurred in 1/6 (17 %) placebo and 1/21 (5 %) seladelpar patients. Liver-related AEs (predefined search strategy) were similar across placebo (2/6, 33 %) and seladelpar (3/21, 14 %). Liver-related laboratory abnormalities (predefined categories) occurred in 2/6 (33 %) placebo-treated and 1/21 (5 %) seladelpar-treated patients. This pooled analysis showed that safety outcomes were overall similar, with no new safety signals between seladelpar and placebo in patients with PBC with cirrhosis and signs of PHT.

Issue

1

First Page

e20

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