Seladelpar Emerges as Key PBC Treatment Post-Obeticholic Acid Withdrawal

The landscape of treatment options for primary biliary cholangitis (PBC) has undergone significant changes following the voluntary withdrawal of obeticholic acid from the US market in September 2025. This decision left a notable gap in therapeutic options for patients unable to respond to or tolerate first-line treatment with ursodeoxycholic acid. In 2024, the introduction of two new second-line therapies—elafibranor and seladelpar—has begun to address this deficiency.

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 highlighting the effectiveness of seladelpar, particularly for patients transitioning from obeticholic acid.

Understanding the Impact of Obeticholic Acid Withdrawal

Dr. Bowlus explained the historical significance of obeticholic acid in the treatment of PBC, especially since its accelerated FDA approval in 2016. Prior to this, patients had limited options, relying mainly on ursodeoxycholic acid for over two decades. Dr. Bowlus noted that approximately 40 to 50 percent of patients did not achieve optimal responses, highlighting the pressing need for effective second-line therapies.

Despite its initial promise, obeticholic acid faced challenges, including adverse effects such as severe itching, which limited its use. Safety concerns, particularly for patients with advanced disease, further complicated its adoption. Its withdrawal created a pressing need for alternative treatments, affecting patients who were stable on obeticholic acid and those who could not tolerate it.

Seladelpar: A Promising Alternative

The approval of seladelpar as a second-line therapy has been a pivotal development. According to Dr. Bowlus, seladelpar demonstrates comparable, if not superior, efficacy to obeticholic acid while also improving itching—a common and distressing symptom of PBC.

At AASLD, Dr. Bowlus presented research derived from a comprehensive administrative database, focusing on patients who switched from obeticholic acid to seladelpar. The findings indicated that patients maintained their biochemical response after the switch, with some even experiencing improvements in alkaline phosphatase levels. This suggests that patients transitioning to seladelpar can anticipate similar, if not enhanced, clinical outcomes.

Despite these promising results, Dr. Bowlus emphasized that several clinical uncertainties remain. One major concern is the long-term efficacy of both new therapies in preventing disease progression. Unlike obeticholic acid, which struggled with long-term approval from regulatory bodies due to efficacy concerns, seladelpar is currently being studied for its long-term impact.

While seladelpar shows a strong safety profile and good efficacy in improving biochemical markers, there remains a significant number of patients who continue to experience disease progression. Dr. Bowlus pointed out that there is an unmet need for third-line therapies or alternative options for this patient population.

In conclusion, with the withdrawal of obeticholic acid, seladelpar emerges as a vital treatment option for PBC, addressing both efficacy and symptom relief. As research continues, the medical community remains hopeful that these new therapies will provide substantial benefits to patients navigating this challenging disease.