Seladelpar Emerges as Key Player in PBC Treatment Following Obeticholic Acid Withdrawal

The withdrawal of obeticholic acid from the U.S. market in September 2025 has left a significant gap in the treatment options for patients suffering from primary biliary cholangitis (PBC). Previously, it was the only second-line therapy available for those who could not tolerate or did not respond to first-line treatment with ursodeoxycholic acid. Following this development, the emergence of new therapies, particularly seladelpar and elafibranor, has reshaped the PBC treatment landscape.

At the recent American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025, Dr. Christopher Bowlus, the Lena Valente Professor and Chief of the Division of Gastroenterology and Hepatology at the University of California Davis School of Medicine, presented new real-world data supporting the use of seladelpar. His findings provide critical insights for clinicians navigating the uncertainties surrounding treatment options after the obeticholic acid withdrawal.

Historical Context of Obeticholic Acid in PBC Treatment

Obeticholic acid received accelerated approval from the U.S. Food and Drug Administration (FDA) in 2016, marking a significant advancement in PBC care. Prior to this, there were no approved second-line therapies, leaving many patients without adequate treatment options. According to Dr. Bowlus, “It had been more than 20 years since that approval, and there were 40 to 50% of patients that we knew did not have an optimal response and remained at risk of disease progression.”

Despite its initial promise, obeticholic acid was associated with adverse effects, particularly severe itching, which limited its utilization among patients who needed it most. Concerns regarding safety in advanced disease stages further complicated its acceptance. The voluntary market withdrawal in the U.S. and Europe left many patients either needing to switch therapies or seeking alternatives, highlighting the need for effective second-line treatments.

Seladelpar’s Role in the New Treatment Landscape

The introduction of seladelpar in 2024 has provided a much-needed alternative for patients. Dr. Bowlus emphasized its significance, noting that “it appears to have similar efficacy to obeticholic acid, if not better, but it also improves itch as opposed to worsening itch.” This improvement in the quality of life for patients suffering from itching due to PBC is a crucial factor in its adoption.

At the AASLD meeting, Dr. Bowlus shared findings from a large administrative database study, which included patients who switched from obeticholic acid to seladelpar. The results indicated that patients maintained their biochemical response, and some even showed improvement in alkaline phosphatase levels. Dr. Bowlus stated, “This is very suggestive of the benefits that patients that are currently on obeticholic and will no longer have access to it can be switched to seladelpar and expect similar, if not better, outcomes.”

Despite these promising findings, uncertainties remain regarding the long-term effects of switching to new therapies. Dr. Bowlus highlighted the ongoing need for research to determine whether these new agents can prevent clinical outcomes, an area where obeticholic acid faced challenges. He reiterated, “There are still patients that remain at risk of disease progression despite two therapies, so there’s still an unmet need for even third-line therapies or other alternative therapies.”

As the landscape of PBC treatment continues to evolve, the introduction of seladelpar represents a significant step forward, offering hope to patients previously reliant on obeticholic acid. Further studies will be essential to fully understand the long-term implications of these new therapies and to address the ongoing needs of this patient population.