Seladelpar’s Long-Term Benefit for Pruritus in PBC, With Gideon Hirschfield, FRCP, PhD

In primary biliary cholangitis (PBC), care is evolving beyond just controlling biochemical markers of disease activity. Now, symptom management is widely viewed as equally important, among the most burdensome being pruritus.

Despite affecting the majority of patients with PBC and having a well-documented negative impact on quality of life, itch often goes underrecognized and undertreated in clinical practice. However, last year’s introduction of seladelpar (Livdelzi) to the PBC treatment landscape may offer clinicians and patients alike a much-needed tool for addressing pruritus.

At the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025, Gideon Hirschfield, FRCP, PhD, director of The Autoimmune and Rare Liver Disease Programme and the Lily and Terry Horner Chair in Autoimmune Liver Disease Research in the division of gastroenterology and hepatology at Toronto General Hospital, presented long-term pruritus outcomes from the RESPONSE study of seladelpar in adults with PBC and interim results from its ongoing open-label extension study, ASSURE, demonstrating sustained, clinically meaningful improvement in itch among patients with moderate to severe pruritus.

“The toolbox for looking after patients has really been augmented over time, far beyond UDCA,” Hirschfield told HCPLive. “Having this choice of drugs, including seladelpar, where there's evidence for biochemical efficacy and there's evidence for pruritus efficacy, really raises the gain for our patients.”

In RESPONSE, pruritus NRS was collected daily for 6 months, then weekly for one week each month through 12 months. Upon rollover to ASSURE, NRS was collected daily for 6 months and then at scheduled clinic visits. Other measures included the 5-D Itch and PBC-40.

Patients with moderate to severe pruritus (NRS ≥4) at baseline were analyzed based on randomization to seladelpar 10 mg or placebo in RESPONSE and reported as continuous or crossover seladelpar 10 mg groups in ASSURE.

Overall, there were 49 seladelpar and 23 placebo patients with pruritus at baseline in RESPONSE. Among them, 33 seladelpar and 17 placebo patients rolled over to ASSURE, and 27 and 16 patients reached 30 months.

Results showed daily NRS was strongly correlated with weekly NRS (r, 0.93; 95% CI, 0.90 to 0.95). Of note, reduction in pruritus with seladelpar in RESPONSE was maintained in ASSURE up to 30 months, with clinically meaningful NRS improvement observed in ≥50% of patients upon seladelpar initiation for crossover patients in ASSURE from 15 months through 30 months.

Mean 5-D Itch total and PBC-40 Itch domain scores were reduced from baseline in continuous seladelpar (−4.6; SE, 0.7; −3.3; SE, 0.7) and crossover seladelpar (−5.8; SE, 1.1; −4.3; SE, 1.0) patients.

“What this presentation does is demonstrate the durability and impact of the improvement of pruritus from seladelpar to be clear and overt and for patients and providers to have a real sense of surety that seladelpar is going to help the patients who are itchy,” Hirschfield said, adding that the data also validates some of the different tools used to measure itch. “We have the tools to assess itch, and now we have the tools to treat it.”

Editors’ note: Hirschfield reports relevant disclosures with CymaBay, Ipsen, Gilead, Intercept, Mirum, Kowa, GSK, Pliant Therapeutics, and Escient.

References

1. Hirschfield G, Kremer A, Levy C, et al. Sustained and Clinically Meaningful Improvements in Moderate to Severe Pruritus Patients With Primary Biliary Cholangitis Treated With Seladelpar: Results From the ASSURE Study up to 30 Months. Presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025. Washington, DC. November 7-11, 2025.

2. Brooks A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. HCPLive. August 14, 2024. Accessed November 8, 2025. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis