Long-term efficacy and safety of selective PPARδ agonist seladelpar in primary biliary cholangitis: ASSURE interim study results

Introduction: The objective of these analyses was to 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. 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 <1.67 upper limit of normal, total bilirubin ≤ upper limit of normal, and alkaline phosphatase 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, among patients who rolled over from RESPONSE, 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. Discussion: Seladelpar demonstrated durable improvements in cholestatic biomarkers and pruritus in patients with primary biliary cholangitis with up to 2 years of treatment and remained overall safe with long-term use. Clinicaltrials.gov: NCT03301506.

Citation

Levy C, Trivedi PJ, Kowdley KV, Gordon SC, Bowlus CL, Londoño MC, Hirschfield GM, Gulamhusein A, Lawitz EJ, Vierling JM, Mayo MJ, Jacobson IM, Kremer AE, Corpechot C, Jones D, Buggisch P, Zhuo S, Proehl S, Heusner C, McWherter CA, Crittenden DB; ASSURE Investigators. Long-Term Efficacy and Safety of Selective PPARδ Agonist Seladelpar in Primary Biliary Cholangitis: ASSURE Interim Study Results. Am J Gastroenterol. 2025 Jun 24. doi: 10.14309/ajg.0000000000003603. Epub ahead of print.

Type

Article