Efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor delta agonist, in primary biliary cholangitis: 52-week analysis of an ongoing international, randomized, dose ranging phase 2 study.
Recommended Citation
Bowlus CL, Neff GW, Aspinall R, Galambos MR, Goel A, Hirschfield G, Kremer A, 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, Landis CS, 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. Efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor delta agonist, in primary biliary cholangitis: 52-week analysis of an ongoing international, randomized, dose ranging phase 2 study. Hepatology 2018; 68(1):1446A-1447A.
Document Type
Conference Proceeding
Publication Date
2018
Publication Title
Hepatol
Abstract
Background: Seladelpar is a potent, selective PPARdelta agonist and a candidate therapy for inflammatory liver diseases. We report the safety and efficacy of daily seladelpar treatment for up to 52 weeks from an ongoing open-label phase 2 study in primary biliary cholangitis (PBC). The 52-week time-point has been previously used for regulatory approval. Methods: This open-label study (NCT02955602) randomized PBC patients with either an inadequate response to ursodeoxycholic acid (UDCA) or an intolerance to UDCA and an alkaline phosphatase (AP) ≥1.67 x upper limit of normal (ULN) to seladelpar 5 or 10 mg. After 12 weeks, patients on 5 mg could escalate to 10 mg if AP treatment goal was not met (5/10 mg group). Follow-up to 52 weeks evaluated dose regimens of 5/10 and 10 mg/day. The primary efficacy outcome was the AP % change from baseline. Other outcomes included a responder analysis defined as a composite of AP<1.67 x ULN, ≥15% decrease in AP, and total bilirubin ≤ULN, as well as changes in liver, metabolic, and inflammatory markers. Pruritus was evaluated with a visual analogue scale (VAS). Safety analyses included adverse events (AE) and laboratory markers. Results: As of 7/2018, 119 patients were exposed to at least one dose of seladelpar. In each group, 17 patients completed 52-week treatment. At baseline, mean (SD) AP were 351 (166) U/L and 279 (74) U/L in the 5/10 and 10 mg groups, respectively. At 52 weeks, the mean decreases in AP were-47% and-46% in the 5/10 and 10 mg groups, respectively. At 52 weeks, 59% and 71% of patients responded to the composite efficacy outcome in the 5/10 and 10 mg groups, respectively. AP normalization occurred in 24% and 29% of patients in the 5/10 and 10 mg groups, respectively. Median ALT decreases were-31% and-33% in the 5/10 and 10 mg groups, respectively. Baseline median VAS were 20 and 41 in the 5/10 and 10 mg groups, respectively. Median changes in VAS were-30% and-66% in the 5/10 and 10 mg groups, respectively. There was no transaminase safety signal. There were 11 serious AEs in the study, none considered related to seladelpar. One discontinuation for a grade 1 gastroesophageal reflux was deemed related to seladelpar. Conclusion: Seladelpar maintained a potent anti-cholestatic effect over 52 weeks. Seladelpar was generally safe, well tolerated and not associated with pruritus. A 52-week phase 3 PBC study has been initiated to confirm these results.
Volume
68
Issue
1
First Page
1446A
Last Page
1447A
