Christopher Bowlus, MD, is the Lena Valente Professor and Chief of the division of gastroenterology and hepatology at the University of California Davis School of Medicine.

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 (

 <.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 

 spoke with Bowlus for the following Q&A:

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

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.

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

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.

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

I think overall, both the liver stiffness data as well as 

 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.

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

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.

Articles

Seladelpar, a selective PPARδ agonist, has been added to the second-line treatment options for primary biliary cholangitis (PBC) following its FDA approval based on the RESPONSE study. This study demonstrated significant efficacy in achieving biochemical response. Recent data from the ASSURE study presented at AASLD 2025 indicate that seladelpar stabilizes or improves liver stiffness measurements (LSMs) over 36 months, suggesting potential for improved clinical outcomes. The treatment's safety profile remains favorable, with no new long-term concerns, reinforcing its role in the evolving PBC treatment landscape.

Bowlus explains clinical outcomes associated with PBC and the importance of assessing liver stiffness over time, highlighting data on seladelpar from AASLD.

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

For many years, obeticholic acid was the sole second-line treatment option for patients with primary biliary cholangitis (PBC) who did not respond to or could not tolerate first-line ursodeoxycholic acid. The September 2025 voluntary withdrawal of obeticholic acid from the US market created a large therapeutic gap.

In 2024, the PBC treatment landscape saw the addition of 2 new second-line therapies in the forms of elafibranor and seladelpar. With obeticholic acid no longer an option, clinical uncertainties have emerged regarding the safety and efficacy of switching these patients to the newly available second-line therapies.

, 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, presented late-breaking, real-world data supporting the use of seladelpar in patients with PBC, including those who switched from obeticholic acid.

For additional insight into the evolving PBC treatment landscape and the seladelpar data presented at AASLD, the editorial team of 

: What role has obeticholic acid has historically played in PBC care since its 2016 accelerated FDA approval? What therapeutic gap was created with its withdrawal this year?

: Prior to 2016, there were no approved therapies other than ursodeoxycholic acid for treatment of patients with PBC. It had been more than 20 years since that approval, and there were 40 to 50% of patients that we knew did not have an optimal response and remained at risk of disease progression. So there was a need for second line therapies, and it was quite difficult to get to that next step where we actually had an approved therapy for second line treatment of PBC, and obeticholic acid was really important in terms of helping those patients and kind of filling that gap.

Unfortunately, obeticholic acid has some adverse effects, particularly itching, that prevented it being used widely in a lot of patients that needed it. There were some concerns about safety, particularly in patients with advanced disease, and then the challenge of demonstrating actual effectiveness of the therapy was another barrier to widespread use. Eventually, it was withdrawn from the market, both here in the US as well as in Europe, kind of for different reasons. Here in the US, it was voluntary by the company to withdraw it. This left patients who were doing quite well on obeticholic acid to need to change therapies as well as those that didn't tolerate it.

Fortunately, we have some additional therapies now, so that's sort of where we're currently at. I would say that the number of patients on obeticholic acid probably has not been growing for some time, so that's the good news, but still, some patients were on it, and some actually would like to continue on it but can't.

: We saw seladelpar added to the PBC 2LT treatment armamentarium last year – what was the significance of this approval?

: Seladelpar was added as a second-line therapy a year ago, and this was significant for a couple of reasons. One is because it appears to have similar efficacy to obeticholic acid, if not better, but it also improves itch as opposed to worsening itch. In patients that have underlying itch from their PBC, seladelpar improves that itch. It was an important step forward in terms of having a new second line agent to help these patients out.

: What does the research you’re presenting at AASLD suggest about the safety and efficacy of seladelpar in patients switching from obeticholic acid?

: The research we are presenting at AASLD looked at the large administrative database of patients that had started seladelpar, including those that had previously been on obeticholic acid and switched over to seladelpar, to see the impact, particularly with biochemistries.

What we saw was that there was at least maintenance of the response that had been seen with obeticholic acid, and, in fact, some improvement in the alkaline phosphatase with the switch. So that's very suggestive of the benefits that patients that are currently on obeticholic and will no longer have access to it can be switched to seladelpar and expect similar, if not better, outcomes in terms of their biochemistries.

: What unanswered questions/clinical uncertainties remain about switching 2LTs in PBC?

I would say it's not just those that are switching, but overall, the bigger question is what are the long term effects of these agents in PBC, and will they be able to demonstrate long term efficacy in terms of preventing clinical outcomes, which is part of the issue that obeticholic acid had in terms of its long term study and getting full approval from the regulatory agencies. So I think that that's the main clinical uncertainty.

We know seladelpar is well tolerated, it has a good safety profile and good efficacy in terms of improving the markers that predict clinical outcomes. There's still patients that remain at risk of disease progression despite 2 therapies, so there's still an unmet need for even third-line therapies or other alternative therapies. There's also symptomatology, because seladelpar improves the pruritus of PBC, the itch, but it doesn't eliminate it in a number of patients.

Bowlus CL, Gordon S, Beltran T, et al. Real-World Experience of Seladelpar Among Patients with Primary Biliary Cholangitis Including Patients Switched from Obeticholic Acid. Presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025. Washington, DC. November 7-11, 2025.

Brooks A. Intercept Voluntarily Withdraws Obeticholic Acid (Ocaliva) for PBC From US Market. HCPLive. September 11, 2025. Accessed November 9, 2025. 

https://www.hcplive.com/view/intercept-voluntarily-withdrawals-obeticholic-acid-ocaliva-for-pbc-from-us-market

Brooks A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. HCPLive. August 14, 2024. Accessed November 9, 2025. 

The withdrawal of obeticholic acid from the US market in 2025 left a significant gap in second-line treatment options for primary biliary cholangitis (PBC). New therapies, elafibranor and seladelpar, have since emerged, with seladelpar showing promise in maintaining or improving biochemical responses in patients switching from obeticholic acid. Despite its efficacy and safety profile, long-term effects and the need for additional therapies remain uncertain. Seladelpar's ability to alleviate pruritus is notable, but it does not completely resolve symptoms for all patients.

Bowlus explains seladelpar’s role in PBC care, including for patients transitioning from obeticholic acid, based on real-world data.