In 2000, troglitazone (GlaxoSmithKline’s Rezulin) was withdrawn from the market due to severe liver toxicity with an unknown mechanism. Troglitazone and other currently marketed drugs, such as rosiglitazone (GlaxoSmithKline’s Avandia) and pioglitazone (Takeda and Eli Lilly’s Actos), are members of a popular class of insulin-sensitizing agents.
The mechanism for troglitazone’s hepatotoxicity is currently unknown, and it is also unknown whether or not agents in the same chemical class may cause similar gene expression changes that could lead to similar toxicity.
Under the terms of the collaboration, Applied Biosystems will investigate the molecular basis of liver toxicity associated with certain diabetes drugs using its proprietary technologies.
The National Center for Toxicological Research of the FDA (FDA/NCTR) plans to analyze the data collected by Applied Biosystems to identify specific genes and pathways associated with liver toxicity and use identified toxicity signatures from the data to predict the toxicity of future drugs in the same chemical class.
“Liver toxicity is a leading cause of drug removal from the market,” said William Murray, division president of the molecular biology division for Applied Biosystems. “We look forward to helping the FDA determine the reason for toxicity induced by troglitazone, and to identifying similarities or differences in the gene expression profile triggered by this drug and other marketed or investigational drugs in the same class.”