New drug candidates often have off-target effects resulting in adverse events, thus representing a major challenge for drug R&D. Safety pharmacology aims to detect, understand and reduce undesirable pharmacodynamic effects early-on. Especially, cardiovascular toxicity is problematic, as it is the most prevalent reason for failure during preclinical development. Moreover, cardiovascular toxicity remains a key reason for drug attrition during clinical development and beyond. While the discipline of safety pharmacology has been successful in identifying drug-induced proarrhythmia risk, new forms of functional and structural (often more chronic) cardiovascular toxicity have emerged. These new cardiovascular liabilities call for new tools for risk identification, assessment, and mitigation. Additionally, safety pharmacology uses a significant number of laboratory animals, thereby creating opportunities for a better implementation of the 3Rs in animal experimentation. The vision of INSPIRE was to extend the toolbox for preclinical safety evaluation by exploring novel technologies and by turning these into new products or services for improved evaluation of drug-induced cardiovascular toxicity. This way, INSPIRE aimed to contribute to more efficiency in drug development and will protect patients from experiencing cardiovascular adverse events. In addition, INSPIRE constituted a stimulating, multidisciplinary and intersectoral training programme for 15 early-stage researchers (ESRs, i.e. PhD students).
Important outcomes of INSPIRE include: i) refinement of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes assays to evaluate structural cardiotoxicity upon long(er)-term drug exposure, ii) improving in vivo telemetry studies by adding automated blood sampling and behavioural monitoring capabilities, iii) exploration of additional hemodynamic parameters beyond blood pressure and iv) delivering new mechanistic insights in the field of cardio-oncology. Finally, through a balanced combination of hands-on research training, intersectoral secondments and network-wide events INSPIRE has equipped a future generation of safety scientists with a wide range of scientific knowledge and professional skills.
