Long-term efficacy and safety of open-label seladelpar treatment in patients with primary biliary cholangitis (PBC): interimresults for 2 years from the ASSURE study
Recommended Citation
Trivedi PJ, Levy C, Kowdley KV, Gordon SC, Bowlus CL, Londoño MC, Hirschfield GM, Gulamhusein A, Lawitz E, Villamil A, Ladrón de Guevara AL, Mayo MJ, Younes ZH, Shibolet O, Yimam K, Pratt D, Heo J, Morgera U, Andreone P, Kremer AE, Corpechot C, Goel A, Peyton A, Elbeshbeshy H, Crittenden DB, Heusner C, Proehl S, Zhou S, McWherter CA. Long-term efficacy and safety of open-label seladelpar treatment in patients with primary biliary cholangitis (PBC): interimresults for 2 years from the ASSURE study. J Hepatol 2024; 80:S98.
Document Type
Conference Proceeding
Publication Date
6-1-2024
Publication Title
J Hepatol
Abstract
Background and aims: Seladelpar, a potent and selective PPAR-delta agonist, has been shown to reduce biochemical markers of cholestasis and pruritus in PBC patients. ASSURE (NCT03301506) is an ongoing, open label, long-term phase 3 trial of seladelpar in patients rolling over from the phase 3 registrational study RESPONSE (NCT04620733) or with prior participation in legacy studies: phase 3 ENHANCE (NCT03602560) study; CB8025–21629 (NCT02955602); CB8025-31731 (NCT03301506); and CB8025-21838 (NCT04950764). Here, we report interim 2-year efficacy and safety results for 337 enrolled patients. Method: Patients with insufficient response or intolerance to first line PBC treatment ursodeoxycholic acid and prior participation in a seladelpar clinical trial could enroll in ASSURE. Key end points were the composite biochemical response (alkaline phosphatase (ALP) <1.67x upper limit of normal (ULN), ALP decrease ≥15%, and total bilirubin ≤ULN) and ALP normalization. Pruritus was reported using a numerical rating scale (NRS; 0–10). Baseline for participants who entered ASSURE from RESPONSE was entry to RESPONSE, analyzed as continuous seladelpar or crossover from placebo. Legacy patients were analyzed separately with baseline set as the entry to ASSURE. Results: As of 31 January 2024, 158 patients from RESPONSE and 179 patients from legacy studies had received 10 mg seladelpar, daily, for up to 155 weeks in ASSURE. In RESPONSE, 61.7% (79 128) of seladelpar patients met the composite end point at Month 12 vs 20% (13 65) for placebo.With continued treatment in ASSURE, 61.8% (63 102) at 6 months in ASSURE and 72.4% (21 29) at 12 months in ASSURE met the composite end point. Among placebo patients crossing over to seladelpar, 75% (39 52) at 6 months and 93.8% (15 16) at 12 months met the composite end point. ALP normalized in 25% of seladelpar and 0 placebo patients at Month 12 in RESPONSE. With continued treatment, 33.3% (6 months) and 17.2% (12 months) had ALP normalization. For crossover patients, 26.9% and 50% had ALP normalization at these timepoints. The change in pruritus NRS with seladelpar in ASSURE was similar to RESPONSE: −3.8 and −3.7 change from baseline at 6 months in continuous and crossover patients, respectively, corresponding to the key secondary end point in RESPONSE. Among legacy patients, 73.2% (120 164) and 69.7% (69 99) met the composite end point at Month 12 and Month 24 in ASSURE. Normalization of ALP was achieved by 42.1% at 12 months and 42.4% at 24 months. Reduction in pruritus NRS in this group was −3.8 at Month 12 and −3.1 at Month 24. The safety profile was favorable with no treatment-related serious adverse events. Conclusion: Continuous treatment with seladelpar for RESPONSE and legacy patients led to sustained effects on biochemical markers and pruritus. Seladelpar appeared safe and well tolerated with longterm use.
Volume
80
First Page
S98
