Drug Safety and Efficacy

Preclinical Drug-Induced Vascular Injury (DIVI) is a phenomenon encompassing a group of histopathologic observations seen in the rat, dog, monkey, and pig that share certain pathologic characteristics. Vascular lesions, primarily arterial, can be induced within hours of drug administration; affected animals may show no clinical signs and in some cases these lesions might be reversible.

DIVI is a frequent finding in pre-clinical toxicity testing of certain pharmacological classes of drug candidates. It is estimated that up to 5% of some companies’ pre-clinical portfolio is affected by DIVI-related safety concerns leading to significant delays or project termination.

DIVI is a preclinical vascular manifestation that develops rapidly in response to drug administration in various vascular beds. Occurrence of DIVI in animal models, however, does not correlate with drug-induced vasculitis occurring in humans, and the lack of appropriate monitoring method is the source of profound safety concerns with some classes of drugs.

Currently, histopathology is the only reliable method of diagnosis for this condition, although promising soluble candidate biomarkers mechanistically linked to the different tissues involved in DIVI have been identified.

The SAFE-T consortium (Safer and Faster Evidence-based Translation) addresses the question of human relevance of preclinical DIVI by qualifying a set of translational biomarkers for the monitoring of DIVI both in preclinical and clinical models. These biomarkers would be key tools to be used by pharmaceutical companies to ensure the vascular safety during the development of new medicines.

Firalis plays a central role in the SAFE-T consortium by co-chairing several of the project working group.