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Toxicol Pathol. 2014 Jun;42(4):658-71. doi: 10.1177/0192623314527644. Epub 2014 Apr 24.

Translation strategy for the qualification of drug-induced vascular injury biomarkers.

Author information

1
Firalis SAS, Biomarker R&D, Huningue, France.
2
Shire, Basingstoke, UK.
3
Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
4
Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
5
Boehringer Ingelheim Pharma GmbH & Co. KG Nonclinical Drug Safety Biberach/Riss, Germany.
6
AstraZeneca Pharmaceuticals, Translational Patient Safety and Enabling Sciences, Wilmington, Delaware, USA.
7
F. Hoffmann-La Roche AG, Basel, Switzerland.
8
Sanofi R&D, Montpellier, France.
9
Sanofi R&D, Vitry-sur-Seine, France.
10
Novartis Pharmaceuticals Corporation, Preclinical safety, East Hanover, New Jersey, USA.
11
Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, F-75013, Paris, France; Département Hospitalo-Universitaire I2B, UPMC Univ Paris 06, F-75005, Paris, France; INSERM UMR 7211, F-75005, Paris, France; INSERM, UMR_S 959, F-75013, Paris, France; CNRS, UMR 7211, F-75005, Paris, France.
12
Pfizer Worldwide Research & Development, Drug Safety Research & Development, Groton, Connecticut, USA michael.lawton@pfizer.com.
13
Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, F-75013, Paris, France; Département Hospitalo-Universitaire I2B, UPMC Univ Paris 06, F-75005, Paris, France; INSERM UMR 7211, F-75005, Paris, France; INSERM, UMR_S 959, F-75013, Paris, France; CNRS, UMR 7211, F-75005, Paris, France patrice.cacoub@gmail.com.

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.

KEYWORDS:

arteritis; biomarker; inflammation; translation.; vascular injury

PMID:
24771082
DOI:
10.1177/0192623314527644
[Indexed for MEDLINE]

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