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

Clinical Snapshot

Key Findings

• P Value: Not reported for this subgroup analysis

• Effect Size: Mean ALP reduction: -37.1% seladelpar vs -10.1% placebo

• Primary Outcome: Composite endpoint achieved by 38.9% seladelpar vs 22.2% placebo at 12 months

• Nnt Or Sensitivity: NNT approximately 6 for composite endpoint achievement (based on 16.7% absolute difference)

• Confidence Interval: Not reported for this subgroup analysis

Clinical Application

Requires specialist hepatology assessment and monitoring for decompensation; oral daily dosing enhances compliance Would require TGA approval; likely PBS listing criteria similar to other PBC therapies; aligns with RACGP chronic disease management principles Patients with PBC and compensated cirrhosis who have inadequate response or intolerance to UDCA

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.

References

1. 1.Gordon, S. C., Villamil, A., Jacobson, I. M., Lawitz, E. J., Younes, Z., Silveira, M. G., Bowlus, C. L., Drenth, J. P. H., Vierling, J. M., Morgera, U., Vasura, A., Dalekos, G., Galli, A., Rabinovitz, M., Heo, J., Nevens, F., Levy, C., Zhou, Y., Carroll, S., & Crittenden, D. B. (2026). Seladelpar in patients with primary biliary cholangitis and compensated cirrhosis: Efficacy and safety from RESPONSE and ASSURE studies. Hepatology Communications. https://doi.org/10.14309/ajg.0000000000003603