Seladelpar Passes First Real-World Test in the Treatment of Primary Biliary Cholangitis

Real-world data presented at The Liver Meeting 2025 in Washington, D.C. suggest that seladelpar is a safe and effective second-line therapy for patients with primary biliary cholangitis (PBC) who were previously treated with obeticholic acid. 

Obeticholic acid (OCA) was used as a second-line therapy for patients with PBC who had suboptimal responses to or were intolerant of ursodeoxycholic acid (UDCA). The recent withdrawal of OCA from the U.S. and European markets due to safety concerns created a need for alternative therapies that can effectively control disease progression and symptoms of PBC. Seladelpar, a selective peroxisome proliferator–activated receptor delta (PPARδ) agonist, was approved in the United States in 2024 for patients with PBC with an inadequate response to or intolerance of UDCA.  

The pivotal phase 3 RESPONSE study included some patients who were previously treated with OCA or fibrates. Early results from the trial showed that seladelpar had similar efficacy and safety in patients with and without prior use of second-line therapies for PBC. Real-world data based on health claims and laboratory values available from August 2023 to June 2025 reinforced the efficacy and safety profile of seladelpar in this population. 

The longitudinal observational cohort study presented at The Liver Meeting included 396 patients who either switched from OCA (130 participants) or initiated seladelpar as monotherapy or as an add-on therapy to UDCA (266 participants), without use of other second-line therapies within the previous 3 months. Most patients who switched from OCA started seladelpar treatment with no gap between OCA and seladelpar prescriptions, with a mean interval of 8 days between the two therapies across the entire OCA-switch group. The median duration of prior OCA treatment was 420 days.

 
Although the follow-up period was limited to the few months following the regulatory approval of seladelpar, the preliminary data showed encouraging trends in people who switched therapies. Reductions in alkaline phosphatase (ALP) levels were observed in both groups, with at least two-thirds of patients achieving ALP levels below 1.67 × ULN in each group. After seladelpar initiation, the proportion of patients who achieved ALP normalization (ALP ≤1 × ULN) increased in both the OCA-switch group and in the second-line seladelpar therapy group. Laboratory values obtained during the monitoring period, which assessed liver and kidney function, remained stable and were similar to those obtained within 90 days before initiating treatment in both groups. Seladelpar was generally well tolerated, with the vast majority (93%) of participants continuing treatment throughout the observation period. 

“Given the relatively short seladelpar observation period, further evaluation with extended follow-up time is warranted,” Christopher Bowlus, MD, Chief of the Division of Gastroenterology and Hepatology at the University of California Davis School of Medicine, and colleagues noted. “[However], these data suggest seladelpar may be an effective and safe alternative for patients with PBC switching from OCA or initiating seladelpar as a second-line therapy in the real world setting.”