Seladelpar’s Impact on Liver Stiffness Measurements in PBC, With Christopher Bowlus, MD

The treatment landscape for primary biliary cholangitis (PBC) has undergone several notable transformations in recent years, among the most significant being the addition of seladelpar to the second-line treatment armamentarium.

The oral, selective peroxisome proliferator-activated receptor delta (PPARδ) agonist’s August 2025 accelerated US Food and Drug Administration approval was based on data from the phase 3 RESPONSE study, which showed 62% of patients treated with seladelpar achieved the primary endpoint of composite biochemical response at month 12 versus 20% of patients taking placebo.

While seladelpar’s efficacy in improving cholestatic markers is well established, its impact on liver stiffness measurements (LSMs), which typically worsen over time in PBC, has remained underexplored. Seeking to address this gap in research, 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, and colleagues reported longitudinal LSM data from an interim analysis of the ongoing phase 3 ASSURE study of seladelpar at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025.

Among the 311 patients included in the analysis, LSM values at 36 months were available in 114 of them. The overall median LSM at baseline was 7.5 (interquartile range [IQR], 5.9 to 11.1) kPa, and the median change in LSM was −0.2 (IQR, −1.7 to 1.8) kPa, with a percent change of −2.9% (IQR, −22.8% to 25.9%).

In patients with baseline LSM of <10.7 kPa, ≥10.7 and <16.9 kPa, or ≥16.9 kPa, median changes in LSM to 36M were +0.1 (IQR, −1.3 to 1.8) kPa, −0.9 (IQR, −3.6 to 4.8) kPa, and −5.2 (IQR, −10.6 to 2.4) kPa, respectively. Similarly, investigators noted median percent changes from baseline were +2.0% (IQR, −18.3 to 26.1), −7.4% (IQR, −29.5 to 38.7), and −29.7% (IQR, −51.5 to 12.7).

For category shifts, results showed 85% of patients were stable or improved at 36 months. Patients whose LSM worsened by ≥ 30% from baseline were younger (P <.05), with otherwise comparable characteristics.

For further insight into the field’s understanding of clinical outcomes in PBC and the LSM data presented at AASLD, the editorial team of HCPLive Hepatology spoke with Bowlus for the following Q&A:

HCPLive: What is known about seladelpar’s impact on cholestatic markers of PBC, and why is it also important to understand its impact on LSM?

Bowlus: The main factors that are associated with clinical outcomes in PBC are liver disease stage, particularly measured by liver stiffness, as well as the alkaline phosphatase and the total bilirubin. The analogy I like to use is that 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. So all these things kind of tell us if someone's early in disease, they could be moving quite fastly with a high alkaline phosphatase but still not reach an outcome. Even someone that's under control, if they have advanced disease, is still at high risk of having an outcome. Besides just improving alkaline phosphatase, we would also like to see stabilization or even improvement in liver stiffness over time.

HCPLive: How do the data you’re presenting at AASLD add to our understanding of seladelpar in this context?

Bowlus: 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. Now liver stiffness is not just a measure of liver fibrosis. It also incorporates cholestasis in there, so some of the improvement may be improvements in cholestasis, but regardless, both of those things are associated with clinical outcomes, so we would expect that improvements or stabilization of liver stiffness over time would be associated with improved clinical outcomes.

HCPLive: How do these data add to our confidence in seladelpar in what has been a rapidly evolving PBC treatment landscape?

Bowlus: 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. 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. So overall, we’re very pleased to have this new therapy available for our patients.

Editors’ note: relevant disclosures for Bowlus include GSK, Ipsen, Gilead, Mirum, Intercept, Cymabay, Amgen, AstraZeneca, TARGET, and others.

References

1. Brooks A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. HCPLive. August 14, 2024. Accessed November 10, 2025. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis

2. Bowlus C, Hirschfield G, Villamil A, et al. Disease Control as Evidenced by Longitudinal Transient Elastography Measurements in the ASSURE Study: 36 Months of Treatment With Seladelpar Is Associated With Stable or Improved Liver Stiffness in Patients With Primary Biliary Cholangitis. Presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025. Washington, DC. November 7-11, 2025.