Bezafibrate for primary biliary cholangitis: time to act on the evidence
Christophe Corpechot et al.
After the regulatory rejection of obeticholic acid, peroxisome proliferator-activated receptor (PPAR) agonists have emerged as the leading second-line candidates for primary biliary cholangitis, pending defnitive approval. Of these, only bezafbrate — a low-cost, widely available generic — has demonstrated long-term efcacy, a fact largely disregarded. Over the past decade, the pharmacological management of primary biliary cholangitis (PBC) — a progressive, potentially life-threatening cholestatic autoimmune-mediated liver disease that primarily affects middle-aged women — has advanced substantially. Although the efficacy of ursodeoxycholic acid (UDCA), the first-line therapy since the 1990s, is now well-supported by both clinical trial data and long-term real-world evidence, second-line options have emerged for individuals with inadequate response or rare intolerance. These options include the farnesoid X receptor agonist obeticholic acid1 , as well as the peroxisome proliferator-activated receptor (PPAR) agonists bezafibrate, elafibranor and seladelpar . To date, however, none of these second-line therapies has obtained full regulatory approval. Notably, after the post-marketing COBALT trial failed to meet expectations5 , the marketing authorization for obeticholic acid was withdrawn in Europe and its full approval revoked in the United States. By contrast, elafibranor and seladelpar were granted accelerated conditional approvals in 2024 and 2025 in both regions, whereas bezafibrate remains widely used off-label worldwide
Fig. 1 | Evidence for bezafibrate in second-line PBC treatment and the crucial questions it raises. Schematic summarizes available clinical trial data (the BEZURSO2 and FITCH7 trials) and real-world data (Sorda et al.8 and Tanaka et al.9 ) in support of bezafibrate as a second-line therapy for management of primary biliary cholangitis (PBC) and highlights key questions this evidence raises for clinicians managing high-risk individuals in need of second-line therapy. ALP, alkaline phosphatase; ALT, alanine transaminase; ELF, enhanced liver fibrosis; LSM, liver stiffness measurement; PPAR, peroxisome proliferator-activated receptor; UDCA, ursodeoxycholic acid.
