Marlyn Mayo, MD, is a professor of internal medicine at UT Southwestern Medical Center.

Marlyn Mayo, MD

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.

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.

, 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.

“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.

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).

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; 

 = .0004), PBC-40 itch domain scores (mean change from baseline, −2.26 vs −1.37; 

 = .0227), 5-D itch total scores (mean change from baseline, −4.85 vs −2.30; 

 <.0001), and 5-D itch degree domain scores (mean change from baseline, −0.96 vs −0.54; 

 = .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.

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.

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.

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

Videos

Mayo explains findings from a pooled analysis of pruritus data from RESPONSE and ENHANCE highlighting seladelpar’s impact on itch in PBC.

 treatment landscape was limited to just a handful of agents with limited efficacy. However, to the excitement of clinicians and patients alike, 2024 saw a major shift in PBC management with the addition of 2 new second-line therapies: elafibranor (Iqirvo) and seladelpar (Livdelzi).

The proliferator-activated receptor (PPAR) agonists earned accelerated approval from the US Food and Drug Administration in June and August, respectively. Whereas obeticholic acid used to be the only other option for patients who do not respond to or cannot tolerate first-line ursodeoxycholic acid, elafibranor and seladelpar offer long-awaited choices for patients who do not benefit from these traditional PBC therapies.

In addition to greatly expanding the PBC treatment landscape, the approvals of elafibranor and seladelpar also provide patients with treatment options that target one of the most common but underrecognized and subsequently undertreated symptoms of PBC: pruritus.

Despite studies reporting pruritus occurrence in 50-80% of PBC cases, Marlyn Mayo, MD, a professor of internal medicine at UT Southwestern Medical Center, explained to 

 how clinicians often underestimate both its prevalence and impact, as evidenced by disparities between patient-reported and physician-assessed pruritus severity. Beyond discomfort, she explained how itch has a profound effect on quality of life, contributing to sleep disturbances, fatigue, anxiety, depression, and functional impairments, including missed work and social isolation.

Marlyn Mayo, MD: Improving Pruritus Management in PBC Care

“Our traditional [PBC] therapies don't help with itch at all and may in fact make it worse,” Mayo said, describing the different guideline-recommended therapies for addressing pruritus in PBC but calling attention to the fact that none of them are universally efficacious.

However, elafibranor and seladelpar may offer viable treatment options for treating both the underlying disease as well as the itch associated with it.

“This is a really exciting time,” Mayo emphasized. “We have just had 2 new drugs approved in the US by the FDA for second-line treatment of PBC, elafibranor and seladelpar, and both of those medications seem to have a beneficial effect on pruritus… For some patients, that might be enough to treat the underlying disease as well as the itching.”

Mayo also expressed optimism about recent advancements in the development of ileal bile acid transporter (IBAT) for treating itch in PBC, with phase 3 trials nearing completion and potentially offering hope for broader application beyond their currently approved pediatric indications.

She went on to emphasize the importance of a nuanced and patient-centered approach to pruritus assessment in patients with PBC, noting the importance of moving beyond binary questioning about the presence of itching to detailed discussions of its severity, quality-of-life impacts, and patient preferences for treatment. Mayo also cites the need for early intervention with guideline-recommended pruritus-directed therapies, especially in patients with severe pruritus who cannot wait the typical 6-12 months to evaluate response to first-line treatment before initiating an itch-effective second-line option like elafibranor or seladelpar.

Editors’ note: Mayo has relevant disclosures with CymaBay, GENFIT, Gilead, GlaxoSmithKline, Ironwood, Intercept, Ipsen, and Mirum.

Brooks, A. FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC. HCPLive. June 10, 2024. Accessed December 9, 2024. 

https://www.hcplive.com/view/fda-grants-accelerated-approval-to-elafibranor-iqirvo-for-pbc

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

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

The treatment landscape for primary biliary cholangitis (PBC) has significantly evolved with the FDA's accelerated approval of elafibranor and seladelpar as second-line therapies. These PPAR agonists offer new options for patients unresponsive to first-line ursodeoxycholic acid, addressing both the disease and pruritus, a common yet often underestimated symptom. The advancements highlight the need for a patient-centered approach to pruritus assessment and early intervention. Additionally, ongoing developments in ileal bile acid transporter therapies may further enhance treatment options for PBC-related itch.

Mayo explains current shortcomings of pruritus care in PBC and what the additions of elafibranor, seladelpar, and other agents in development may offer.

Marlyn Mayo, MD

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