Seladelpar Had a Positive Impact on Liver Stiffness Over 3 Years

Seladelpar may alter the trajectory of primary biliary cholangitis (PBC) by improving a key marker of disease progression, according to new data from the phase 3 ASSURE study. The interim analysis of the ongoing, open-label clinical trial, presented at The Liver Meeting 2025, in Washington, D.C., showed that patients with PBC treated with seladelpar maintained or improved their liver stiffness measurements over 3 years of treatment. 

PBC is a chronic autoimmune liver disease characterized by cholestasis and progressive fibrosis. In patients who experience advanced fibrosis or cirrhosis, liver stiffness worsens over time, despite treatment with ursodeoxycholic acid (UDCA), which is used as a first-line therapy for PBC. The degree of liver stiffness is an important risk stratification tool that can be used to predict the risk of liver-related events and mortality. Studies have shown that higher liver stiffness values are linked to a greater risk of all-cause mortality, decompensated cirrhosis, and liver cancer (Singh S et al. Clin Gastroenterol Hepatol 2013;11:1573-84). 

In the phase 3, placebo-controlled RESPONSE trial, participants treated with seladelpar 10 mg daily achieved improvements in cholestatic markers, such as significant reductions in alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels. RESPONSE enrolled individuals with PBC who had an inadequate response to UDCA or could not tolerate the first-line therapy. Participants in the RESPONSE trial and those from legacy seladelpar studies were subsequently enrolled in the ongoing, open-label phase 3 ASSURE study, which was designed to evaluate the long-term efficacy and safety of treatment with seladelpar. 

The interim analysis presented at The Liver Meeting provided new insight into the long-term impact of seladelpar on liver stiffness progression in 114 patients who received treatment for up to 3 years, through January 31, 2025. All participants in ASSURE who received open-label seladelpar 10 mg and had at least one post-baseline liver stiffness measurement were included in the analysis. Nearly 80% of the patients with initial liver stiffness values ≥16.9 kPa had confirmed cirrhosis at baseline. Changes in liver stiffness were assessed at 12, 24, and 36 months after treatment initiation with the use of vibration-controlled transient elastography (FibroScan). 

The results showed that treatment with seladelpar led to overall stable liver stiffness measurements in patients with PBC. Most participants (85%) demonstrated either stable or improved liver stiffness values at the 36-month scan. A trend toward improvement in liver stiffness was seen in treated patients with the highest risk of progression, who had liver stiffness measurements ≥16.9 kPa at baseline, suggesting that seladelpar may be able to slow progression and reverse the course of disease even in patients with advanced PBC.