BMS-986234 / BMS - LARVOL DELTA

Mechanism of hepatobiliary toxicity of the LPA antagonist BMS-986020 developed to treat idiopathic pulmonary fibrosis: Contrasts with BMS-986234 and BMS-986278. (PubMed, Toxicol Appl Pharmacol) - "The data indicate that this toxicity was unrelated to LPA antagonism since the mechanisms that likely influenced the adverse clinical outcome of BMS-986020 were not observed with equipotent LPA antagonists BMS-986234 and BMS-986278. This conclusion is consistent with the lack of hepatobiliary toxicity in nonclinical and clinical safety studies with BMS-986278."

Journal • Fibrosis • Gastroenterology • Hepatology • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • ABCC3

Structure dependence and species sensitivity of in vivo hepatobiliary toxicity with lysophosphatidic acid receptor 1 (LPA) antagonists. (PubMed, Toxicol Appl Pharmacol) - "BMS-986020, BMS-986234 and BMS-986278, are three lysophosphatidic acid receptor 1 (LPA) antagonists that were or are being investigated for treatment of idiopathic pulmonary fibrosis (IPF). Mixed effects on plasma bile acids in both rat and monkey has made this biomarker not a useful predictor of the hepatobiliary toxicity. In conclusion, the nonclinical data indicate the hepatobiliary toxicity observed clinically and in monkeys administered BMS-986020 is compound specific and not mediated via antagonism of LPA."

Journal • Preclinical • Cholestasis • Developmental Disorders • Fibrosis • Gastroenterology • Hepatology • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases