FDA Qualifies Glutamate Dehydrogenase (GLDH) Biomarker to Enhance Liver Safety Monitoring in Clinical Trials + + + + +

Drug Development Tools | DDTs https://www.fda.gov/drugs/development-approval-process-drugs/drug-development-tools-ddts?utm_medium=email&utm_source=govdelivery FDA Qualifies Glutamate Dehydrogenase (GLDH) Biomarker to Enhance Liver Safety Monitoring in Clinical Trials https://force-dsc.my.site.com/ddt/s/ddt-project?ddtprojectid=94&utm_medium=email&utm_source=govdelivery The U.S. Food and Drug Administration (FDA)’s Center for Drug Evaluation and Research has qualified glutamate dehydrogenase (GLDH) as a safety biomarker to detect possible drug-induced liver injury (DILI) in conjunction with alanine aminotransferase (ALT) and other standard liver injury markers in clinical trials, particularly in participants with elevated transaminases due to muscle injury. For example, patients with Duchenne muscular dystrophy can have elevated ALT due to muscle degeneration, which can confound a DILI signal. In these situations, GLDH can provide additional information to help make a DILI determination. Innovation in biomarker development for drug safety monitoring is greatly needed, particularly for patients with muscle disorders where traditional liver injury markers can be confounded by muscle damage. GLDH is a more liver-specific enzyme that was validated as capable of detecting hepatocellular injury. Unlike ALT, which is released from both liver and muscle tissue, GLDH is primarily expressed in the liver and remains unaffected by muscle injury or degeneration. This liver specificity enables better detection of possible hepatocellular DILI in populations where muscle damage could otherwise confound such liver safety assessment. The qualification statement completes the review of the full qualification package that the Critical Path Institute's Predictive Safety Testing Consortium submitted and defines the context in which FDA will accept GLDH as a safety biomarker for regulatory decisions. Drug development tools play an important role in bringing new therapies to the market. They include biomarkers, which are defined biological characteristics; clinical outcome assessments, which describe how patients feel, function, or survive; and certain animal models. For more information: DDT Qualification Programs https://www.fda.gov/drugs/development-approval-process-drugs/drug-development-tool-ddt-qualification-programs?utm_medium=email&utm_source=govdelivery Qualification Process for Drug Development Tools Guidance for Industry and FDA Staff https://www.fda.gov/regulatory-information/search-fda-guidance-documents/qualification-process-drug-development-tools-guidance-industry-and-fda-staff?utm_medium=email&utm_source=govdelivery CDER & CBER Drug Development Tool Qualification Project Search https://force-dsc.my.site.com/ddt/s/?utm_medium=email&utm_source=govdelivery