Letter of Support for drug-induced liver injury clinical safety biomarkers

The U.S. Food and Drug Administration (FDA), recently, issued Biomarker Letters of Support for the drug-induced liver injury safety biomarkers Cytokeratin 18 (CK-18), Total and hyperacetylated high mobility group protein B1 (HMGB1), Osteopontin, and Macrophage colony-stimulating factor 1 receptor (CSF1R) based on data submitted by the Innovative Medicine Initiative’s (IMI) Safer and Faster Evidence-based Translation Consortium (SAFE-T) and the Critical Path Institute’s (C-Path) Predictive Safety Testing Consortium’s (PSTC) Hepatotoxicity Working Group (HWG).

This letter, issued to SAFE-T and PSTC, briefly describes U.S. FDA CDER’s thoughts on the value of CK-18, HMGB1, Osteopontin, and CSF1R and encourages further evaluation. The U.S. FDA’s Letter of Support encourages further evaluation of biomarkers with promising utility in drug development either “alone or in combination as soluble monitoring biomarkers to assess the risk of progression of drug-induced liver injury (DILI) in patients in whom an initial DILI diagnosis has been established based on elevations of the standard biomarkers alanine aminotransferase (ALT) alone or in combination with total bilirubin (TBIL) as a clinical safety assessment in clinical trials in a drug development context.”