Long-term Efficacy and Safety of Selective PPARδ Agonist Seladelpar in Primary Biliary Cholangitis: ASSURE Interim Study Results.

Abstract

OBJECTIVES Evaluate interim data from the ongoing, open-label, long-term efficacy and safety ASSURE study of seladelpar, a selective peroxisome proliferator-activated receptor δ agonist, in primary biliary cholangitis (PBC). METHODS Patients rolling over from the phase 3, randomized, placebo-controlled, 12-month RESPONSE study or with previous participation in earlier legacy seladelpar studies were enrolled. Interim evaluations included composite biochemical response (alkaline phosphatase [ALP] <1.67×upper limit of normal [ULN], total bilirubin ≤ULN, and ALP decrease ≥15%), pruritus numerical rating scale (NRS) change among patients with a baseline score ≥4, and safety. RESULTS At interim cutoff, 337 patients were enrolled and received ≥1 seladelpar 10-mg dose; 54 placebo-treated and 104 seladelpar-treated from RESPONSE and 179 from legacy studies. The composite response rate at RESPONSE completion was 62% (79/128) with seladelpar and 20% (13/65) with placebo. After 12 months in ASSURE, response rates were 72% (21/29) in patients continuing seladelpar and 94% (15/16) in crossover seladelpar patients. In legacy trial patients, response rates were 73% (120/164) and 70% (69/99) after 12 and 24 months of treatment in ASSURE, respectively. The NRS decrease at RESPONSE completion in seladelpar-treated patients with baseline NRS ≥4 (-3.4) was maintained after 6 additional months of treatment (-3.8); changes were similar in crossover seladelpar (-3.8) and legacy patients (-3.5) after 6 months of treatment in ASSURE. No seladelpar-related serious adverse events were reported. CONCLUSIONS Seladelpar demonstrated durable improvements in cholestatic biomarkers and pruritus in patients with PBC with up to 2 years of treatment and remained overall safe with long-term use.