Investigational farnesoid X receptor agonists for the treatment of primary biliary cholangitis.
Expert Opin Investig Drugs
; 33(6): 627-638, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38676426
ABSTRACT
INTRODUCTION:
Up to 40% of Primary biliary cholangitis (PBC) patients have a suboptimal response to Ursodeoxycholic acid (UDCA). Close to half of such patients show a remarkable improvement when additionally treated with Obeticholic acid (OCA) but have a dose-dependent increase of pruritus. This relative success of OCA, a first-in-class Farnesoid receptor (FXR) agonist, has positioned FXR as an attractive target for drug development. Novel candidates have since emerged, providing hope for this subgroup of patients who lack effective and safe treatments. AREAS COVERED We discussed the role of bile acids in PBC pathogenesis and how the FXR agonists provide therapeutic value by affecting bile acid synthesis and transport. Novel FXR agonists undergoing pre-clinical and clinical trials for PBC were enlisted via literature search by including the terms 'FXR agonists,' 'FXR PBC,' 'PBC clinical trials' on PubMed, MEDLINE via Ovid, and Clinicaltrials.gov. EXPERT OPINION Novel FXR agonists currently under investigation for PBC improve the disease surrogate markers in early trials. However, as with OCA, pruritus remains a concern with the newer drugs despite targeted chemical modifications to increase FXR specificity. Directing future resources toward studying the molecular mechanisms behind pruritus may lead to better drug design and efficacious yet safer drugs.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Ácido Quenodesoxicólico
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Receptores Citoplasmáticos y Nucleares
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Cirrosis Hepática Biliar
Idioma:
En
Revista:
Expert Opin Investig Drugs
Asunto de la revista:
TERAPIA POR MEDICAMENTOS
Año:
2024
Tipo del documento:
Article