Seladelpar for the Treatment of Primary Biliary Cholangitis.

Abstract

Objective: To review the published data including the pharmacology, efficacy, and safety of seladelpar, a peroxisome proliferator-activated receptor delta (PPARδ) agonist leading to the Food and Drug Administration (FDA) accelerated approval for the treatment of primary biliary cholangitis (PBC).

Data sources: A PubMed (January 1, 1985 to January 27, 2025) literature search was performed using the terms seladelpar, MBX-8025, peroxisome proliferator-activated receptor agonist, and PBC. Other data sources included Google Scholar and the National Institutes of Health Clinical Trials Registry.

Study selection and data extraction: All English-language literature evaluating the pharmacology, pharmacokinetics, safety, and efficacy of seladelpar in the treatment of PBC was reviewed.

Data synthesis: Seladelpar is the first PPARδ agonist in the treatment of PBC that has shown a significant reduction across biochemical response, alkaline phosphatase (ALP) normalization, and pruritus as compared to placebo while demonstrating safety and tolerability.Relevance to patient care and clinical practice in comparison to existing drugs:While existing drug treatments for PBC are efficacious, there remains an unmet need due to an incomplete biochemical response in many patients. Patients frequently suffer from symptoms, including pruritus, impacting their quality of life. Seladelpar could have a beneficial role in PBC as add-on therapy in improving biochemical response as well as alleviating pruritus.

Conclusion: Seladelpar is a safe and effective treatment for PBC and fills a significant unmet need. Seladelpar's clinical benefit predicted by improvement in surrogate endpoints may need confirmation for traditional FDA approval.