New Insights Into Seladelpar for PBC at AASLD 2025, With Andreas Kremer, MD, PhD

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. However, in 2024, the PBC treatment landscape saw the addition of 2 new second-line therapies, one being the oral, selective peroxisome proliferator-activated receptor delta (PPARδ) agonist seladelpar.

The August 2024 accelerated 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.

At the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025, new data provided clinicians with additional insight into seladelpar’s benefit for patients with PBC, including its disease-modifying and symptom-relieving effects. In an on-site interview at the conference, Andreas Kremer, MD, PhD, head of hepatology at University Hospital Zurich, broke down some of the key research and its clinical implications.

“[Seladelpar] has proven to be efficacious in a phase 3 study in regard to anticholestatic, anti-inflammatory properties, but there was also a prespecified secondary endpoint in regard to worst itch NRS improvement that was met, and this was very convincingly shown for those patients with moderate to severe pruritus,” Kremer explained to HCPLive.

At AASLD, late-breaking RESPONSE and ASSURE open-label extension study data shed light on long-term pruritus outcomes with seladelpar, highlighting sustained, clinically meaningful improvement in itch among patients with moderate-to-severe pruritus in RESPONSE and with up to 30 months of treatment.

Additional analyses from RESPONSE showed improvements in itch-related disability and decreased bodily distribution of itch following treatment with seladelpar as well as greater improvements in their general health and wellbeing after 12 months.

“This adds on to the antipruritic properties of this drug, which is very reassuring, and we have also seen efficacy for several years,” Kremer said.

Editors’ Note: Relevant disclosures for Kremer include AbbVie, AstraZeneca, Bayer, CymaBay, Gilead, GlaxoSmithKline, Intercept, Mirum, Takeda, Ipsen, and others.

References

1. Brooks A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. August 14, 2024. Accessed November 12, 2025. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis

2. Hirschfield G. Seladelpar’s Long-Term Benefit for Pruritus in PBC, With Gideon Hirschfield, FRCP, PhD. HCPLive. November 8, 2025. Accessed November 12, 2025. https://www.hcplive.com/view/seladelpar-long-term-benefit-pruritus-pbc-with-gideon-hirschfield-frcp-phd

3. Kremer A, Jones DE, Mayo M, et al. Reduction in Itch-Associated Disability and Pruritus Distribution in Patients With Primary Biliary Cholangitis Treated With Seladelpar in the RESPONSE Trial. Presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025. Washington, DC. November 7-11, 2025.

4. Kumar S, Kremer A, Londono MC, et al. Improvements in Patient-Reported General Health and Well-Being in Patients With Primary Biliary Cholangitis Treated With Seladelpar in the RESPONSE Trial. Presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025. Washington, DC. November 7-11, 2025.