EMA Offers Support for More Research on DIVI Biomarkers

Regulatory NewsRegulatory News | 09 November 2017 |  By 

European Medicines Agency (EMA) Executive Director Guido Rasi this week sent a letter of support to the Safer and Faster Evidence-Based Translation (SAFE-T) Consortium and the Predictive Safety Testing Consortium (PSTC) to encourage further study of ways to monitor for drug-induced vascular injury (DIVI) in early clinical drug development.

"Drug-induced vascular injury in nonclinical animal toxicology studies can cause considerable delays in the drug development process and promising candidate drugs are often terminated as the occurrence of DIVI cannot be monitored or substantiated in healthy volunteer or patient trials due to the absence of specific, sensitive biomarkers," Rasi wrote.

The termination of such research has led to a wider search for circulating biomarkers that can detect, in a sensitive and specific manner, the onset, progression and reversibility of DIVI, Rasi said.

"The only currently available biomarkers used to assess the potential for vascular injury in early clinical studies are non‐specific markers of inflammation, markers of immune-mediated drug reactions (for large molecules), and for compounds that are systemically 'vasoactive' in nonclinical studies, heart rate and blood pressure," he wrote. "Having more sensitive and specific DIVI biomarkers would allow drug development teams to manage DIVI as a monitorable nonclinical finding. With these tools a team could safely advance potential new medicines, including both small molecules and large molecules, which cause nonclinical DIVI into clinical studies at safety margins not previously possible without such DIVI biomarkers, thus enabling exploration of clinically efficacious doses."

Rasi's letter, dated 7 November, follows the sending of a similar letter to the same groups by the US Food and Drug Administration's (FDA) Center for Drug Evaluation and Research Director Janet Woodcock on 7 November 2016.

Rasi also called for further data sharing and integrating data across trials to foster an accelerated path for biomarker qualification.

Letter of support for drug-induced vascular injury (DIVI) biomarker


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