Efficacy, safety, and tolerability of seladelpar in patients with compensated liver cirrhosis due to primary biliary cholangitis (PBC): a pooled analysis of phase 2 and phase 3 studies
Recommended Citation
Gordon SC, Trivedi P, Bowlus C, Michael G, Goel A, Gulamhusein A, Levy C, Neff G, Stanca C, Thorburn D, Bacon B, Borg B, Doerffel Y, Forman L, Freilich B, Gheorghe L, González MS, Harrison S, Huang J, Jeong S, Kim SU, Lake J, Odin J, Tak WY, Tobias H, Vierling JM, Yang K, Steinberg A, Choi Y, McWherter C. Efficacy, safety, and tolerability of seladelpar in patients with compensated liver cirrhosis due to primary biliary cholangitis (PBC): a pooled analysis of phase 2 and phase 3 studies. J Hepatol 2021; 75(2):S686-S687.
Document Type
Conference Proceeding
Publication Date
7-1-2021
Publication Title
J Hepatol
Abstract
Background and aims: Patients with PBC and compensated cirrhosis can progress to decompensation with its associated complications, liver transplantation or death. PBC patients with an incomplete response or intolerance to UDCA have an unmet need to slow disease progression. Seladelpar, a selective PPAR delta agonist, has shown potent anti-cholestatic and anti-pruritic activity in PBC studies. We now report a pooled analysis from two studies assessing the efficacy, safety, and tolerability of seladelpar in PBC patients with compensated cirrhosis. Method: Eligible PBC patients with an inadequate response or intolerance to UDCA (ALP ≥1.67 × ULN) were enrolled into an openlabel phase 2 study (EudraCT 2016-002996-91) or a placebo (Pbo)-controlled phase 3 study (EudraCT 2018-001171-20). Cirrhosis was diagnosed using liver biopsy, imaging tests, or liver elastography. Patients received oral Pbo, seladelpar 5 mg or 10 mg once daily + UDCA if tolerated. Efficacy analyses at 3 months included composite response (ALp <1.67 × ULN, ALP decrease of ≥15% and total bilirubin [TB] ≤ULN), ALP % change, ALP ≤ULN, and changes in liver function. Safety was assessed for 3 months. Results: Of 384 enrolled patients, 53 had compensated cirrhosis (Child-Pugh A: Pbo [n = 7], 5 mg [n = 22], and 10 mg [n = 24]). Baseline characteristics included: 92% female, mean age 58 yrs, 94% on UDCA, ALP 287 U L, TB 0.92 mg dL, ALT 50 U L, AST 49 U L, GGT 228 U L, albumin 3.96 g dL, and platelets 197 × 103 μL. After 3 months, 39 patients were treated. The composite end point was met in 50% (9 18) of 5 mg and 63% (10 16) of 10 mg groups compared to none in Pbo (0 5). Reductions in ALP in the 5 mg (-31%, − 82 U L) and 10 mg groups (−41%, −114 U L) were greater than Pbo (−2.6%, −8.7 U L). ALP was normalized in 3 patients in each seladelpar group (17–19%) but none in Pbo. Changes in ALT were −15%, −6%, and −32% in Pbo, 5 and 10 mg groups, respectively. Total bilirubin, platelets, albumin, and INR remained stable. One patient in 10 mgdiscontinued due to AE (pruritus). Three patients had an SAE: 2 on 5 mg (febrile neutropenia, procedural pain) and 1 on 10 mg (angina pectoris), all unrelated to study drug. Efficacy, tolerability, and safety in patients with compensated cirrhosis were comparable to that of non-cirrhotic patients. Conclusion: Seladelpar appeared safe and was well tolerated and may provide an effective treatment option for patients with compensated liver cirrhosis due to PBC. [Figure presented]
Volume
75
Issue
2
First Page
S686
Last Page
S687
