Seladelpar in patients with primary biliary cholangitis and compensated cirrhosis: Efficacy and safety from RESPONSE and ASSURE studies

Authors

• Stuart C. Gordon, Henry Ford HealthFollow
• Alejandra Villamil
• Ira M Jacobson
• Eric J Lawitz
• Ziad Younes
• Marina G Silveira
• Christopher L Bowlus
• Joost P H Drenth
• John M Vierling
• Ulrike Morgera
• Adam Vasura
• George Dalekos
• Andrea Galli
• Mordechai Rabinovitz
• Jeong Heo
• Frederik Nevens
• Cynthia Levy
• Yan Zhou
• Susheela Carroll
• Daria B Crittenden

Recommended Citation

Gordon SC, Villamil A, Jacobson IM, Lawitz EJ, Younes Z, Silveira MG, Bowlus CL, Drenth JPH, Vierling JM, Morgera U, Vasura A, Dalekos G, Galli A, Rabinovitz M, Heo J, Nevens F, Levy C, Zhou Y, Carroll S, Crittenden DB. Seladelpar in patients with primary biliary cholangitis and compensated cirrhosis: Efficacy and safety from RESPONSE and ASSURE studies. Hepatol Commun. 2026;10(5).

Document Type

Article

Publication Date

5-1-2026

Publication Title

Hepatol Commun

Keywords

Humans, Female, Liver Cirrhosis, Biliary, Middle Aged, Treatment Outcome, Male, Alkaline Phosphatase, Aged, Liver Cirrhosis, PPAR delta, Bilirubin, Adult, Thiazoles, Propionates, Chalcones

Abstract

BACKGROUND: Treatment options are limited for patients with primary biliary cholangitis (PBC) and cirrhosis. Seladelpar, a first-in-class delpar (selective PPAR-δ agonist), had generally similar efficacy and safety among patients with versus without compensated cirrhosis in the phase 3 RESPONSE study. Here we provide additional data on seladelpar in patients with compensated cirrhosis from the phase 3 program.

METHODS: In RESPONSE, patients with PBC and an inadequate response or intolerance to UDCA were randomized 2:1 to seladelpar 10 mg or placebo for 1 year. Upon completion, patients rolled over into the open-label (seladelpar 10 mg) phase 3 ASSURE study, which also enrolled patients from earlier seladelpar legacy PBC studies. Here, we assessed the composite endpoint [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ALP decrease ≥15%, and total bilirubin ≤ULN], other laboratory changes, and safety in all patients with cirrhosis from RESPONSE and an interim analysis of the ongoing ASSURE study through January 2024.

RESULTS: Twenty-seven patients with compensated cirrhosis enrolled in RESPONSE (18 seladelpar, 9 placebo). At month 12, 38.9% and 22.2% of patients in the seladelpar and placebo groups, respectively, met the composite endpoint; mean percent change from baseline in ALP was -37.1% and -10.1%, respectively. Upon rollover to ASSURE (13 seladelpar, 6 placebo), ALP declines were maintained for up to 18 months. An additional 35 patients with compensated cirrhosis in ASSURE from legacy studies had similar reductions in ALP with up to 2 years of treatment. Bilirubin remained overall stable. No treatment-related serious adverse events occurred. Variceal bleeding and/or ascites developed in 3 patients after ≥9 months.

CONCLUSIONS: Seladelpar decreased markers of cholestasis and was overall safe and well-tolerated in patients with PBC and compensated cirrhosis.

Medical Subject Headings

Humans; Female; Liver Cirrhosis, Biliary; Middle Aged; Treatment Outcome; Male; Alkaline Phosphatase; Aged; Liver Cirrhosis; PPAR delta; Bilirubin; Adult; Thiazoles; Propionates; Chalcones

PubMed ID

41974026

Volume

10

Issue

5