Seladelpar Shows Promise in Stabilizing Liver Stiffness in Primary Biliary Cholangitis Patients
Key Insights
Seladelpar, a newly approved second-line therapy for primary biliary cholangitis (search) (PBC (search)), demonstrated stabilization or improvement in liver stiffness measurements over 36 months in the ongoing ASSURE study.
The phase 3 data showed 85% of patients maintained stable or improved liver stiffness measurements, with the greatest improvements observed in patients with the highest baseline liver stiffness values.
These findings add confidence to seladelpar's clinical utility beyond biochemical improvements, suggesting potential for better long-term outcomes in PBC (search) patients who don't respond to first-line therapy.
New data from the ongoing phase 3 ASSURE study of seladelpar reveal that the recently approved second-line therapy for primary biliary cholangitis (search) (PBC (search)) not only improves biochemical markers but also stabilizes liver stiffness measurements over time, offering additional evidence of the drug's clinical benefit.
Christopher Bowlus, MD, the Lena Valente Professor and Chief of the division of gastroenterology and hepatology at the University of California Davis School of Medicine (search), presented the longitudinal liver stiffness measurement (LSM) data at the American Association for the Study of Liver Diseases (search) (AASLD (search)) The Liver Meeting 2025.
Liver Stiffness Stabilization Across Patient Groups
The interim analysis included 311 patients, with LSM values at 36 months available for 114 participants. The overall median LSM at baseline was 7.5 kPa, and the median change in LSM was −0.2 kPa, representing a percent change of −2.9%.
The data revealed differential responses based on baseline liver stiffness severity. Patients with baseline LSM of <10.7 kPa showed a median change of +0.1 kPa (+2.0% change). Those with LSM ≥10.7 and <16.9 kPa experienced a median change of −0.9 kPa (−7.4% change). Most notably, patients with the highest baseline LSM (≥16.9 kPa) demonstrated the greatest improvement with a median change of −5.2 kPa (−29.7% change).
Clinical Significance Beyond Biochemical Markers
"The main factors that are associated with clinical outcomes in PBC (search) are liver disease stage, particularly measured by liver stiffness, as well as the alkaline phosphatase and the total bilirubin," Bowlus explained. He described the relationship using an analogy: "The FibroScan and the total bilirubin tell you where along the disease process a patient is at, where on the roadmap, whereas the alkaline phosphate tells you the rate at which they're going along that road."
The study showed that 85% of patients were stable or improved at 36 months. Patients whose LSM worsened by ≥30% from baseline were younger, with otherwise comparable characteristics.
Expanding Treatment Options in PBC
Seladelpar received accelerated FDA approval in August 2025 based on data from the phase 3 RESPONSE study, where 62% of patients treated with seladelpar achieved the primary endpoint of composite biochemical response at month 12 versus 20% of patients taking placebo.
The approval significantly expanded the PBC (search) treatment landscape. As Ann Moore, NP, from Arizona Liver Health (search) noted at the 2025 Gastroenterology & Hepatology Advanced Practice Providers conference, "2024 brought the FDA approvals, but 2025 brought real world experience using these new medications." She emphasized that second-line options are essential for the 40% of patients who do not respond to or cannot tolerate first-line ursodeoxycholic acid (UDCA).
Implications for Patient Care
Bowlus noted that liver stiffness measurements incorporate both fibrosis and cholestasis, both of which are associated with clinical outcomes. "What we've seen is that the liver stiffness does at least remain stable, if not improve over time, in patients that are treated with seladelpar," he said.
The findings suggest that seladelpar's benefits extend beyond biochemical improvements. "I think overall, both the liver stiffness data as well as the switch data and other emerging data, are all consistent with an effect of seladelpar that is not just biochemical, but likely to translate into improved clinical outcomes," Bowlus stated.
Moore emphasized the importance of considering patient symptoms alongside biochemical measures: "We have great second line therapies and we need to think about them early, we need to monitor and treat early and individualize patient care, because now we can, because we have options."
The safety profile continues to be favorable, with Bowlus noting, "In terms of safety profile, we're continuing to see that it has good safety, and there are no new concerns about long term use."