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 definitive approval. Of these, only bezafibrate — a low-cost, widely available generic — has demonstrated long-term efficacy, a fact largely disregarded.
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References
Nevens, F. et al. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N. Engl. J. Med. 375, 631–643 (2016).
Corpechot, C. et al. A placebo-controlled trial of bezafibrate in primary biliary cholangitis. N. Engl. J. Med. 378, 2171–2181 (2018).
Kowdley, K. V. et al. Efficacy and safety of elafibranor in primary biliary cholangitis. N. Engl. J. Med. 390, 795–805 (2024).
Hirschfield, G. M. et al. A phase 3 trial of seladelpar in primary biliary cholangitis. N. Engl. J. Med. 390, 783–794 (2024).
Kowdley, K. V. et al. COBALT: a confirmatory trial of obeticholic acid in primary biliary cholangitis with placebo and external controls. Am. J. Gastroenterol. 120, 390–400 (2025).
Jones, D. E. J. et al. Primary biliary cholangitis drug evaluation and regulatory approval: where do we go from here? Hepatology 80, 1291–1300 (2024).
de Vries, E. et al. Fibrates for itch (FITCH) in fibrosing cholangiopathies: a double-blind, randomized, placebo-controlled trial. Gastroenterology 160, 734–743.e6 (2021).
Sorda, J. A. et al. Bezafibrate therapy in primary biliary cholangitis refractory to ursodeoxycholic acid: a longitudinal study of paired liver biopsies at 5 years of follow up. Aliment. Pharmacol. Ther. 54, 1202–1212 (2021).
Tanaka, A. et al. Association of bezafibrate with transplant-free survival in patients with primary biliary cholangitis. J. Hepatol. 75, 565–571 (2021).
Martins, A. et al. Comparative effectiveness of peroxisome proliferator–activated receptor agonists as second-line therapies for primary biliary cholangitis: a systematic review and network meta-analysis. Hepatology https://doi.org/10.1097/HEP.0000000000001465 (2025).
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C.C. reports grants from Intercept Pharmaceuticals and Arrow Génériques, and consulting work for Cymabay, Gilead, Ipsen, Calliditas, GSK, Mirum, Advanz, Echosens and Intercept Pharmaceuticals; M.-C.L. reports grants from Gilead and Mirum; consulting work for Advanz, Mirum, Gilead, Ipsen, Falk and GSK; and lectures for Advanz, GSK, Gilead and Ipsen. H.Y. reports advisory board participation for IPSEN and congress participation by invitation from IPSEN. A.V. reports speaker fees from Intercept. A.T. reports consultant work for GSK, Kowa, Kaken Pharmaceuticals, Ipsen, Mirum, AbbVie and Gilead. U.B. reports consulting and/or lecture fees from Abacus, Amgen, Behring, GSK, Ipsen, Mirum and Ono.
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Corpechot, C., Londoño, MC., Villamil, A. et al. Bezafibrate for primary biliary cholangitis: time to act on the evidence. Nat Rev Gastroenterol Hepatol (2025). https://doi.org/10.1038/s41575-025-01135-y
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DOI: https://doi.org/10.1038/s41575-025-01135-y
