Emerging Therapeutics for Primary Biliary Cholangitis

Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by progressive destruction of the intrahepatic bile ducts, potentially leading to cirrhosis and end-stage liver disease. Ursodeoxycholic acid (UDCA) has been the standard first-line therapy, but up to one-third of patients show an unsatisfactory response to UDCA, underscoring the need for novel treatments. Obeticholic acid is an approved second-line treatment targeting the farnesoid X receptor, but it is associated with adverse effects such as pruritus and the potential risk of hepatic decompensation in patients with advanced disease. Recently, selective peroxisome proliferator-activated receptor (PPAR) agonists, including seladelpar (a PPAR-δ agonist) and elafibranor (dual PPAR-α/δ agonist), have shown substantial efficacy and favorable safety profiles in phase three clinical trials. In addition, emerging therapeutics for symptom relief, such as NOX inhibitors and ileal bile acid transporter inhibitors, further expand the treatment options. These advances offer new opportunities for the improved management of patients with PBC.