Translation Strategy for the Qualification of Drug-induced Vascular Injury Biomarkers

Kaïdre Bendjama, Silvia Guionaud, Gulfidan Aras, Nadir Arber, Lina Badimon, Uwe Bamberger, Dorina Bratfalean, David Brott, Maayan David, Lucette Doessegger, Hüseyin Firat, Jean François Gallas, Jean Charles Gautier, Peter Hoffmann, Sarah Kraus, Teresa Padro, David Saadoun, Piotr Szczesny, Peter Thomann, Gemma VilahurMichael Lawton, Patrice Cacoub

Research output: Contribution to journalArticlepeer-review

Abstract

Drug-induced vascular injury (DIVI) is a common preclinical toxicity usually characterized by hemorrhage, vascular endothelial and smooth muscle damage, and inflammation. DIVI findings can cause delays or termination of drug candidates due to low safety margins. The situation is complicated by the absence of sensitive, noninvasive biomarkers for monitoring vascular injury and the uncertain relevance to humans. The Safer And Faster Evidence-based Translation (SAFE-T) consortium is a public–private partnership funded within the European Commission’s Innovative Medicines Initiative (IMI) aiming to accelerate drug development by qualifying biomarkers for drug-induced organ injuries, including DIVI. The group is using patients with vascular diseases that have key histomorphologic features (endothelial damage, smooth muscle damage, and inflammation) in common with those observed in DIVI, and has selected candidate biomarkers associated with these features. Studied populations include healthy volunteers, patients with spontaneous vasculitides and other vascular disorders. Initial results from studies with healthy volunteers and patients with vasculitides show that a panel of biomarkers can successfully discriminate the population groups. The SAFE-T group plans to seek endorsement from health authorities (European Medicines Agency and Food and Drug Administration) to qualify the biomarkers for use in regulatory decision-making processes.

Original languageEnglish
Pages (from-to)658-671
Number of pages14
JournalToxicologic Pathology
Volume42
Issue number4
DOIs
StatePublished - Jun 2014
Externally publishedYes

Keywords

  • arteritis
  • biomarker
  • inflammation
  • translation
  • vascular injury

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