Seladelpar’s Impact on Pruritus in Primary Biliary Cholangitis, With Marlyn Mayo, MD

Primary biliary cholangitis (PBC) remains a challenging chronic liver disease in which symptom management is just as important as controlling biochemical markers of disease activity. Among the most burdensome symptoms is pruritus, which affects the majority of patients and can severely diminish quality of life, yet often goes underrecognized and undertreated in clinical practice.1

As new therapies emerge, the treatment landscape for PBC is undergoing rapid change, offering clinicians and patients renewed hope for both disease control and symptom relief. Against this backdrop, recent data on the selective PPAR-delta agonist seladelpar presented at the American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting by Marlyn Mayo, MD, a professor of internal medicine at UT Southwestern Medical Center, are providing important insight into how modern therapies can address not only biochemical response but also the persistent challenge of itch in PBC.1

In an interview with HCPLive, Mayo emphasized that following Intercept Pharmaceuticals’ recent voluntary withdrawal of obeticholic acid from the US market, an influx of patients will need to find a new second-line therapy, raising questions about how clinicians will use the 2 currently available options and their impact on itch.2

“One of the things that I presented was the characteristics in the [seladelpar] phase 3 study of itching, and it was very striking to me that only 25% of the patients who put on the questionnaires that they had moderate to severe itch were actually getting any kind of therapy for their itch, which goes to show you how bad we are at treating that symptom, even in centers that are doing research in PBC that are supposed to be centers of excellence,” Mayo said, referencing findings from a pooled post-hoc analysis of pruritus outcomes from the RESPONSE and ENHANCE trials.1

Of the 126 participants in the trials with moderate to severe pruritus, 76 and 50 pts received seladelpar 10 mg and placebo, respectively, in RESPONSE or ENHANCE. At baseline, most patients were < 50 years of age at the time of PBC diagnosis (n = 73) and had a history of pruritus (n = 122) and fatigue (n = 77).1

Data presented at ACG showed that at 6 months, compared with placebo, patients who received seladelpar experienced greater improvements in NRS scores (mean change from baseline, −3.12 vs −2.09; P = .0004), PBC-40 itch domain scores (mean change from baseline, −2.26 vs −1.37; P = .0227), 5-D itch total scores (mean change from baseline, −4.85 vs −2.30; P <.0001), and 5-D itch degree domain scores (mean change from baseline, −0.96 vs −0.54; P = .0005). Of note, the safety profiles in patients with pruritus in the seladelpar and placebo groups were similar, with adverse events occurring in 76.3% of seladelpar patients and 80% of placebo patients.1

While Mayo acknowledged seladelpar’s apparent benefit for relieving itch, she notes that the medication in its currently approved indication “fulfills a very specific niche” for ursodeoxycholic acid nonresponders who experience pruritus. For patients who respond well to ursodeoxycholic acid but still deal with itching, seladelpar is not yet an option.

“This drug is not approved for that indication, and we don't have data in that situation, so I think that is still an unfulfilled need,” Mayo said. “There are drugs that are being studied for that purpose, and hopefully someday we'll have something.”

Editors’ Note: Mayo reports relevant disclosures with CymaBay Therapeutics, GSK, Ipsen, Mirum Pharma, and more.

References

1. Jones DEJ, Levy C, Kremer AE, et al. Change in Pruritus in Patients With Primary Biliary Cholangitis and Moderate to Severe Pruritus: A Pooled Analysis From the RESPONSE and ENHANCE Studies. Presented at the American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting. Phoenix, Arizona. October 27-29, 2025.

2. Brooks A. Intercept Voluntarily Withdraws Obeticholic Acid (Ocaliva) for PBC From US Market. HCPLive. September 11, 2025. Accessed October 30, 2025. https://www.hcplive.com/view/intercept-voluntarily-withdrawals-obeticholic-acid-ocaliva-for-pbc-from-us-market