S1881 Long-Term Efficacy and Safety of Open-Label Seladelpar Treatment in Patients With Primary Biliary Cholangitis: Interim Results for 2 Years From the ASSURE Study

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Introduction: Seladelpar reduces biochemical markers of cholestasis and pruritus in patients (patients) with primary biliary cholangitis (PBC). ASSURE (NCT03301506) is an ongoing, open label, long-term Phase (Ph) 3 trial of seladelpar in patients rolling over from the Ph 3 registrational study RESPONSE (NCT04620733) or with prior participation in legacy studies (Ph 3 ENHANCE [NCT03602560], CB8025-21629 [NCT02955602], CB8025-31731 [NCT03301506], and CB8025-21838 [NCT04950764]). Here, we report interim 2-year efficacy and safety results. Methods: Patients with insufficient response/intolerance to first-line PBC treatment ursodeoxycholic acid and past participation in a seladelpar clinical trial could enroll in ASSURE. Key endpoints were the composite biochemical response (alkaline phosphatase [ALP] < 1.67× upper limit of normal [ULN], ALP decrease ≥15%, and total bilirubin ≤ULN) and ALP normalization. Pruritus was measured via numerical rating scale (NRS; 0–10). For patients entering ASSURE from RESPONSE, baseline (BL) was entry to RESPONSE and analyzed as continuous seladelpar or crossover from placebo (PBO); legacy patients were analyzed separately, with BL defined as entry to ASSURE. Results: As of 01/31/2024, 158 (RESPONSE) and 179 (legacy) patients received seladelpar 10 mg daily for up to 155 weeks in ASSURE. In RESPONSE, 61.7% (79/128) of seladelpar patients met the composite endpoint at 12 months (M) vs 20% (13/65) for PBO. With continued treatment in ASSURE, 61.8% (63/102) at 6M and 72.4% (21/29) at 12M met the composite endpoint. Among PBO patients crossing over to seladelpar, 75% (39/52) at 6M and 93.8% (15/16) at 12M met the composite endpoint. ALP normalized in 25% of seladelpar and 0 PBO patients at 12M in RESPONSE. With continued treatment, 33.3% (6M) and 17.2% (12M) had ALP normalization; for crossover patients, 26.9% and 50% had ALP normalization. Change from BL in pruritus NRS with seladelpar in ASSURE was similar to RESPONSE: −3.8 and −3.7 at 6M in continuous and crossover patients, respectively, corresponding to the key secondary endpoint in RESPONSE. Among legacy patients, 73.2% (120/164) and 69.7% (69/99) met the composite endpoint at 12M and 24M in ASSURE; at 12M and 24M, 42.1% and 42.4% achieved ALP normalization and change from BL in pruritus NRS was −3.8 and −3.1, respectively. There were 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 long-term use.

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