Effect of seladelpar on pruritus in primary biliary cholangitis: 26-week analysis of an ongoing international, randomized, dose ranging phase 2 study. Hepatology 2018; 68(1):1464A-1465A.

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Background: Primary biliary cholangitis (PBC) is an idiopathic inflammatory liver disease characterized by the destruction of intrahepatic bile ducts. Up to 70% of patients experience pruritus during the course of the disease, a symptom that can dramatically reduce the quality of life. Seladelpar is a potent and selective peroxisome proliferator-activated receptor delta agonist which is a candidate therapy for patients with inflammatory liver diseases. We report here the effect of seladelpar on pruritus after 26 weeks of treatment in an ongoing phase 2 PBC study. Methods: This open-label study (NCT02955602) investigates PBC patients with an alkaline phosphatase (AP) ≥1.67 x upper limit of normal (ULN) having either an inadequate response to ursodeoxycholic acid (UDCA) or an intolerance of UDCA. Patients were randomized to receive either 5 or 10 mg. After 12 weeks, patients in the 5 mg group could titrate to 10 mg based on their AP response (5/10 mg group). Data evaluated through the first 26 weeks represent a key regulatory timepoint to assess pruritus. Patients recorded itch intensity on a visual analogue scale (VAS) ranging from 0 to 100, 0 representing no pruritus and 100 unbearable pruritus. Additional pruritus questionnaires (5-D itch, PBC-40) were collected, as well as medical history and adverse events. Results: As of 7/2018, 119 patients received at least one dose of seladelpar, of whom 79 (66%) reported a history of pruritus. 37 patients contributed to the week 26 interim analysis (VAS > 0 at baseline), 18 patients in the 5/10 mg group and 19 in the 10 mg group. Baseline median VAS were 15 (range 1-68) and 50 (range 5-90) in the 5/10 mg and 10 mg groups, respectively. At 26 weeks, median changes in VAS were-50% and-55% in the 5/10 mg and 10 mg groups, respectively. There were no serious adverse events due to pruritus. Pruritus was reported as an adverse event in 24/119 (20%) patients. One patient entered the study with intense pruritus and discontinued seladelpar 10 mg after 5 days due to an increase in pruritus, possibly related to PBC. At 26-week, there were no discontinuations related to seladelpar. Conclusion: In this population of PBC patients, seladelpar was not associated with drug-induced pruritus. It is hypothesized that seladelpar treatment could reduce pruritus intensity. A phase 3 study has been initiated to evaluate pruritus and confirm these results over 26-weeks in a placebo-controlled setting.





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