Seladelpar in Primary Biliary Cholangitis

Review by Prof. Ahad Eshraghian (Iran)

Study Summary 

Primary biliary cholangitis (PBC) is a chronic, cholestatic liver disease characterized by destruction of small, intrahepatic biliary epithelial cells resulting in chronic choletatsis, biliary fibrosis, and liver cirrhosis. Ursodeoxycholic acid (UDCA) is the first line treatment for PBC but more than 40% of patients have inadequate response. Obeticholic acid was approved in 2016 as the second line treatment, however, nearly half of patients had poor clinical response even with exacerbation of pruritus. In a randomized controlled trial, patients with PBC and inadequate clinical response to UDCA were randomized to receive seladelpar (a peroxisome proliferator–activated receptor delta agonist) or placebo for 12 months. Patients who received seladelpar had greater alkaline phosphatase normalization and biochemical response with significantly reduced pruritus.

Commentary 

The study demonstrated that seladelpar (a peroxisome proliferator–activated receptor delta agonist) was effective in treatment of patients with PBC who were unresponsive to UDCA therapy. Of note, no major adverse events was reported and in contrast to obeticholic acid, pruritus was significantly decreased with seladelpar in patients with moderate-to-severe pruritus at baseline. While results of the study is promising in treatment of patients with PBC, there are still proportion of patients who had inadequate response to seladelpar and may benefit from combination therapies.

Citation

Hirschfield GM, et al. A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis. N Engl J Med. 2024 Feb 29;390(9):783-794. doi: 10.1056/NEJMoa2312100. Epub 2024 Feb 21. PMID: 38381664.

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