Seladelpar Demonstrated Long-Term Efficacy and Safety in the Treatment of Primary Biliary Cholangitis

The latest data from the open-label ASSURE clinical trial, presented at The Liver Meeting 2025, in Washington, D.C., showed that patients with primary biliary cholangitis (PBC) maintained improvements in biochemical markers of cholestasis over 3 years of treatment with seladelpar, which was generally well tolerated. 

“Ursodeoxycholic acid (UDCA) has been the cornerstone of PBC treatment for many years,” Daniel Pratt, MD, an assistant professor of medicine at Harvard Medical School, in Boston, noted during a presentation at The Liver Meeting. “However, approximately 40% of our PBC patients will have an inadequate response to UDCA and are desperately in need of safe and effective second-line therapies. With the recent withdrawal of obeticholic acid from the markets in both the United States and Europe, this leaves peroxisome proliferator-activated receptor (PPAR) agonists as a second-line therapy.” 

Seladelpar, a first-in-class PPAR-delta agonist, was approved in the United States in 2024 as an add-on therapy for adults with PBC who have an inadequate response to UDCA or as a monotherapy for those who cannot tolerate this first-line therapy. Seladelpar has anticholestatic and anti-inflammatory effects, and has been shown to reduce pruritus and increase lipid metabolism. 

In the pivotal phase 3 RESPONSE study, seladelpar led to statistically significant improvements in cholestatic biomarkers and pruritus, and was well tolerated over 12 months of treatment. Some of the participants who received either seladelpar (104 people) or placebo (54 people) in RESPONSE subsequently enrolled in ASSURE, an ongoing, 5-year, open label study that was designed to assess the long-term safety and efficacy of seladelpar in the treatment of PBC. ASSURE also enrolled 179 patients from previous legacy studies of seladelpar, who had a 2-year gap before resuming seladelpar treatment. 

Preliminary results from ASSURE showed that seladelpar demonstrated sustained efficacy up to 24 months and maintained a favorable safety profile in patients treated up to 36 months. A new analysis of data recorded up to January 31, 2025 showed that a majority of the patients treated with seladelpar achieved a composite biochemical response, defined as alkaline phosphatase (ALP) levels < 1.67 X ULN and a decrease in ALP levels of at least 15% from baseline, as well as total bilirubin normalization, at each timepoint assessed over 3 years of treatment. Moreover, approximately one-third of patients achieved a complete normalization of the ALP levels at each timepoint. Total bilirubin remained stable over 36 months of seladelpar treatment, with 90% of patients achieving or maintaining normal bilirubin levels. 

“The ultimate endpoint for PBC therapy is to achieve a deep response, defined as a complete normalization of both ALP and of total bilirubin [levels]” Pratt said. “The deep response endpoint was achieved in approximately one-third of the patients, and that response was sustained over 36 months.” 

The analysis also showed that seladelpar treatment resulted in rapid and sustained reductions in alanine aminotransferase (ALT) levels. “Of the 150 patients who had elevated ALT [levels] at baseline, approximately 60% normalized their ALT over time with seladelpar treatment, which may reflect improvements in inflammation and associated liver injury,” Pratt noted. GLOBE scores, which are used to assess response to treatment and progression of disease in PBC, also improved with seladelpar treatment, suggesting an improved prognosis for treated patients. Approximately one-third of patients had moderate-to-severe pruritus, defined as a numeric rating scale (NRS) score of 4 or greater, at baseline. Seladelpar led to a rapid and clinically meaningful improvement in moderate-to-severe pruritus in these patients, which was sustained over 36 months. 

After 4 years of treatment exposure, 18% of the participants experienced serious adverse events. However, no serious or fatal events were related to the treatment, and the overall incidence of adverse events remained stable over time. 

“ASSURE provides important long-term data on the use of seladelpar in patients with PBC,” Pratt concluded. “This latest analysis from ASSURE continues to demonstrate sustained improvements in biochemical markers of cholestasis up to 36 months in patients with PBC treated with seladelpar, and [this therapy] continues to shows an overall favorable safety profile in patients with PBC after 4 years of treatment.”