Long-term safety and efficacy of seladelpar in patients with primary biliary cholangitis (pbc): 2-year results from a long-term study

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Conference Proceeding

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Background: Seladelpar is a potent and selective peroxisome proliferator activated receptor-delta agonist shown to improve markers of cholestasis and symptoms in PBC patients. We evaluated the safety and efficacy of seladelpar during 2 years of treatment in patients with PBC. Methods: Eligible PBC patients with an inadequate response or intolerance to UDCA (ALP ≥ 1.67xULN) were enrolled into an open-label one-year phase 2 study (NCT02955602). Patients received oral daily doses of 2, 5 or 10 mg seladelpar. After 12 weeks the dose could be increased up to 10 mg based on ALP response. The primary endpoint was percent change in ALP. After 1 year, patients were eligible for an open label long-term study (NCT03301506). A total of 103/106 patients from the phase 2 study entered the long-term study. We evaluated the safety and efficacy of these 103 patients for up to 2 years of seladelpar treatment. Results: Of 103 patients (5/10 mg [17] and 10 mg [86]) entering the long-term study from the oneyear study, most were female (94%) with a mean age of 57±9 years, mean duration of PBC 10±7 years, and mean UDCA dose of 15±4 mg/kg/day. Mean baseline values in the 5/10 mg and 10 mg groups were: ALP 323 U/L and 319 U/L, TB 0.70 mg/dL and 0.80 mg/dL, GGT 259 U/L and 241 U/L, and ALT 46 U/L and 49 U/L. The long-term study was terminated due to atypical biopsy findings in a concurrent NASH trial, which were later found to be unrelated to seladelpar. At termination, 97 patients remained in the study (94%) and 53 patients (51%; 12 on 5 mg, 41 on 10 mg) had completed 2 years of treatment with seladelpar. The mean ALP percnt change from baseline was -42% and -50% after 1 and 2 years, respectively (1A). The composite biochemical response (ALP <1.67xULN with ≥15% decrease and normal TB) was 64% and 79% after 1 and 2 years, respectively (1B). ALP levels normalized in 24% and 42% of patients at 1 and 2 years, respectively (1C). Over 2 years, there were sustained reductions in ALT, AST, and GGT, but TB and platelets remained stable. Three patients discontinued seladelpar due to AEs. SAEs occurred in 21 patients, but none were related to seladelpar, and 20/21 continued or resumed treatment. The most common AEs were pruritus, nausea, and fatigue. Conclusion: Longterm treatment with seladelpar for 2 years appeared safe, was well tolerated, and resulted in reductions in biomarkers of cholestasis and hepatocellular injury with continued improvement observed between years 1 and 2.

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