Critical Path Institute (C-Path) today announced that the Biomarker Qualification Program (BQP) at the Center for Drug Evaluation and Research (CDER) in the U.S. Food and Drug Administration (FDA) issued a Biomarker Letter of Support (LOS) for four pancreatic injury safety biomarkers identified and evaluated by C-Path's Predictive Safety Testing Consortium's (PSTC) Pancreatic Injury Working Group (PIWG).
This set of biomarkers will help increase the ability to detect and monitor drug-induced pancreatic injury (DIPI) to better inform dosing-related decisions in clinical trials for new drugs.
The biomarkers in question are microRNAs (miRNAs), namely – miR-216a, miR-216b, miR-217, and miR-375. In conjunction with the current standard biomarkers, amylase and lipase, the four novel biomarkers represent sensitive tools to detect DIPI in phase 1 clinical trials, when preclinical information suggests the potential to cause DIPI.
Sensitive DIPI biomarkers permit earlier detection of potential injury and determine if a novel therapy can be monitored for potential injury in humans better than the current options. This will improve the accuracy of clinical monitoring and increase the safety of healthy volunteers and patients, also optimizing the overall cost of clinical development of new drugs.
In its LOS, FDA stated, "We support PSTC's initiative to encourage the voluntary and complementary use of these miRNAs in conjunction with amylase and lipase as exploratory nonclinical and clinical biomarkers of DIPI. We also support PSTC's generation of additional nonclinical toxicology data and plan for exploratory early clinical studies to enable future formal qualification of these safety biomarkers."
Collaboration and data sharing between PSTC's members advanced us to this important step in the path to implementing safety biomarkers with the potential to improve detection of DIPI in drug development."
Nicholas King, Executive Director, Predictive Safety Testing Consortium, Critical Path Institute (C-Path)
Senior Director, Systems Toxicology, Nonclinical Drug Safety at Merck & Co., Inc. and PSTC PIWG Co-Chair Warren Glaab, Ph.D., indicated, "The FDA Letter of Support is a significant milestone demonstrating the added value of emerging safety biomarkers for drug-induced pancreatic injury. This also represents the first endorsement of miRNAs as safety biomarkers to monitor the onset of drug-induced injury. The Letter of Support also provides the foundation for further translation to clinical settings and will further enable clinical qualification of these safety biomarkers."
Michael Ringenberg, Ph.D., Senior Scientific Director, Pathology, at GlaxoSmithKline and PIWG Co-Chair, said, "Through the identification of promising monitorable parameters, this LOS reinforces our consortia's commitment to strengthened vigilance over drug safety in patients."