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

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.

American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025

, 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.

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

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. 

https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis

Articles

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.