Exploring Seladelpar as Monotherapy for PBC, with Stuart Gordon, MD

New research is shedding light on the safety and efficacy of seladelpar (Livdelzi) as monotherapy in patients with primary biliary cholangitis (PBC) and an intolerance to ursodeoxycholic acid (UDCA).1

The data were presented at Digestive Disease Week (DDW) 2025 by Stuart Gordon, MD, a professor of medicine at Wayne State University School of Medicine and director of the division of hepatology at Henry Ford Hospital, and suggest use of the selective PPARδ agonist as monotherapy yields similar safety and efficacy results as those observed for seladelpar combined with UDCA.1

“The treatment landscape for PBC has evolved remarkably over the past year,” Gordon told HCPLive, citing the US Food and Drug Administration approvals of 2 new second-line agents.

In August 2024, the US Food and Drug Administration approved seladelpar for the treatment of PBC in combination with UDCA in adults who have had an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA.2 In a pair of phase 3 placebo-controlled studies, ENHANCE and RESPONSE, treatment with seladelpar led to a significantly greater rate of composite biochemical response and alkaline phosphatase (ALP) normalization compared to placebo.1

Gordon and colleagues conducted a post hoc analysis of pooled efficacy and safety data for seladelpar 10 mg monotherapy versus placebo from ENHANCE and RESPONSE through month 3 to assess the effects of treatment with seladelpar alone. In these studies, patients intolerant to UDCA were eligible if their last dose was >3 months before study entry.1

In total, 369 patients were randomly assigned to seladelpar 10 mg or placebo across both studies, 16 of whom received seladelpar monotherapy and 6 of whom received placebo without UDCA. Investigators noted mean baseline ALP was similar between monotherapy patients receiving seladelpar vs placebo.1

At month 3, 62% of patients receiving seladelpar monotherapy demonstrated a composite biochemical response compared with 17% receiving placebo, and 23% of patients on seladelpar achieved normalized ALP versus no patients on placebo. Additionally, the mean percent change from baseline in ALP at month 3 was −46% with seladelpar versus −2% with placebo.1

At month 3, 56% of patients on seladelpar monotherapy experienced an adverse event (AE) compared with 83% on placebo, but no serious AEs and no discontinuations due to AEs occurred through month 3 with seladelpar monotherapy.1

However, Gordon notes there is still much work to be done when it comes to PBC treatment research and education.

“There's so many unmet needs. We have very good therapy, and now we have even better therapy, but we need to see how that therapy plays out in terms of improvement of outcomes… we're anxious to look at real-world evidence outcomes,” he explained, additionally calling attention to the importance of educating both patients and physicians on PBC.

Editors’ note: Gordon has relevant disclosures with AbbVie, Arbutus, CymaBay, DURECT, Genfit, Gilead, GSK, Hightide, Intercept, Mirum, Pliant, and Merck.

References

1. Gordon SC, Neff G, Rodriguez M, et al EFFICACY AND SAFETY OF SELADELPAR AS MONOTHERAPY IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS AND INTOLERANCE TO URSODEOXYCHOLIC ACID. Abstract presented at Digestive Disease Week 2025 in San Diego, CA, from May 3 - May 6, 2025.

2. Brooks A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. HCPLive. August 14, 2024. Accessed May 5, 2025. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis