Translation strategy for the qualification of drug-induced vascular injury biomarkers.
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.
Firalis SAS, Biomarker R&D, Huningue, France.
Kaïdre
K
Bendjama
Shire, Basingstoke, UK.
Silvia
S
Guionaud
Firalis SAS, Biomarker R&D, Huningue, France.
Gulfidan
G
Aras
Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Nadir
N
Arber
Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Lina
L
Badimon
Boehringer Ingelheim Pharma GmbH & Co. KG Nonclinical Drug Safety Biberach/Riss, Germany.
Uwe
U
Bamberger
Firalis SAS, Biomarker R&D, Huningue, France.
Dorina
D
Bratfalean
AstraZeneca Pharmaceuticals, Translational Patient Safety and Enabling Sciences, Wilmington, Delaware, USA.
David
D
Brott
Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Maayan
M
David
F. Hoffmann-La Roche AG, Basel, Switzerland.
Lucette
L
Doessegger
Firalis SAS, Biomarker R&D, Huningue, France.
Hüseyin
H
Firat
Sanofi R&D, Montpellier, France.
Jean-François
JF
Gallas
Sanofi R&D, Vitry-sur-Seine, France.
Jean-Charles
JC
Gautier
Novartis Pharmaceuticals Corporation, Preclinical safety, East Hanover, New Jersey, USA.
Peter
P
Hoffmann
Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Sarah
S
Kraus
Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Teresa
T
Padro
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.
David
D
Saadoun
F. Hoffmann-La Roche AG, Basel, Switzerland.
Piotr
P
Szczesny
Firalis SAS, Biomarker R&D, Huningue, France.
Peter
P
Thomann
Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Gemma
G
Vilahur
Pfizer Worldwide Research & Development, Drug Safety Research & Development, Groton, Connecticut, USA michael.lawton@pfizer.com.
Michael
M
Lawton
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.
Patrice
P
Cacoub
D015415:Biomarkers / Q000097:blood*; D003657:Decision Making; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D005060:Europe; D006801:Humans; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology; D055818:Public-Private Sector Partnerships; D015203:Reproducibility of Results; D057170:Translational Research, Biomedical; D014481:United States; D014486:United States Food and Drug Administration; D057772:Vascular System Injuries / Q000139:chemically induced* / Q000473:pathology*
D015415:Biomarkers
arteritis; biomarker; inflammation; translation.; vascular injury