Host: The Japanese Society of Toxicology
Biomarkers are invaluable drug development tools to assess and monitor safety in early clinical trials especially when exposure margins are limiting for promising therapeutics. Although progress is made towards identifying and implementing translational safety biomarkers for a number of organ toxicities such as kidney and liver, significant gaps still exist to monitor toxicities for testis, pancreas, etc. Several precompetitive consortia (eg., PSTC, IMI) are working with industry, academia, government, patient advocacy groups and foundations with a goal to qualify biomarkers such that they can be used in preclinical studies and clinical trials to accelerate drug development. This talk will provide examples of how unique miRNA (miRNA profiling), protein (eg, gastrin) and low molecular weight molecules/metabolite (eg, bile acids, hyaluronic acid, norepinephrine) biomarkers are used as exploratory biomarker tools to understand mechanistic aspects of organ toxicity. In addition, the talk will also provide examples to demonstrate the complexities of biomarker discovery, validation and regulatory qualification intended for clinical trial applications. Examples include 1) regulatory qualification of GLDH to address the specificity gaps of ALT and 2) efforts to qualify biomarkers for skeletal muscle injury/dystrophy for their potential use in clinical trials for Duchene muscular dystrophy. As part of the global qualification of biomarkers, there are international efforts led by PSTC Japan that include leading Japanese scientists and pharmaceutical companies to advance qualification of emerging safety biomarkers at PMDA for clinical use in Japanese population. These efforts will not only increase the contributions of Japanese scientists in biomarker working groups but also provide annotated bio specimens from Japanese subjects to bridge the biomarker data needed for qualification. These efforts will be discussed.
