Seladelpar As a PPAR-δ Agonist in PBC: Pharmacological Insights and Clinical Applications

Primary biliary cholangitis (PBC) is an autoimmune disease that is characterized by the continuous destruction of small bile ducts within the liver, primarily affecting women aged 40-65. The condition leads to cholestasis and potential liver failure, necessitating effective treatment strategies. Seladelpar (MBX-8025) is a novel selective peroxisome proliferator-activated receptor (PPAR)-delta agonist that has been pioneered to address the unmet need in PBC management. Recent trials demonstrate that seladelpar significantly reduces alkaline phosphatase (ALP) levels and improves patients overall biochemical response, particularly in those intolerant or nonresponsive to UDCA. Particularly, seladelpar regulates bile acid metabolism via suppression of CYP7A1 and elevation of FGF21, contributing to its anti-inflammatory and antifibrotic actions. As a promising experimental drug, seladelpar could reshape treatment approach for PBC, providing an alternative treatment for patients who do not respond adequately to existing therapies due to inadequate responses.