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.
Kremer A, Bowlus CL, Neff GW, Aspinall R, Galambos MR, Goel A, Hirschfield G, Mayo MJ, Swain MG, Borg B, Dörffel Y, Gordon SC, Harrison SA, Jones D, Thuluvath PJ, Levy C, Heridan DAS, Stanca CM, Bacon BR, Berg C, Hassanein TI, Odin J, Shiffman ML, Thorburn D, Vierling JM, Bernstein D, Buggisch P, Corless L, Andis CSL, Peyton AL, Shah HA, Woerns MA, Gitlin N, Steinberg A, Bergheanu S, Amato G, Choi YJ, Rosenbusch S, Varga M, McWherter C, and Boudes P. 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.
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.