INSPIRE — INnovation in Safety Pharmacology for Integrated cardiovascular safety assessment to REduce adverse events and late stage drug attrition.

Results in brief

INnovation in Safety Pharmacology for Integrated cardiovascular safety assessment to REduce adverse events and late stage drug attrition.

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.

Data: CORDIS, © European Union

Project objective

New drug candidates often have off-target effects resulting in adverse events, thus representing a major limitation for drug R&D. Safety Pharmacology (SP) aims to detect, understand and reduce undesirable pharmacodynamic effects early-on. Especially, cardiovascular (CV) toxicity is problematic, as it is the most prevalent reason for failure during preclinical development. Moreover, CV toxicity remains a key reason for drug attrition during clinical development and beyond. This indicates current SP screens fail to detect a number of (late-onset) functional or structural CV toxicities. Additionally, SP uses a significant number of laboratory animals, thereby creating opportunities for a better implementation of the 3Rs. The vision of INSPIRE is to advance and “inspire” SP by exploring new technological capabilities (WP1), addressing emerging CV concerns (WP2) and delivering new validated solutions for CV safety screening (WP3). To this end, INSPIRE unites expertise from academic teams, technology-providers, pharmaceutical companies, regulators and hospitals to create a European training platform for 15 Early Stage Researchers (ESRs). Key innovative aspects of INSPIRE include: i) in vitro humanized cardiomyocytes assays, ii) unparalleled in vivo hardware/software solutions, iii) in silico predictions of haemodynamics, iv) mass spectroscopy imaging of drug exposure, v) exploration of mechanisms of late-onset CV toxicity, as observed in cardio-oncology, and vi) early integration of feedback from industry and regulators. Overall, INSPIRE constitutes a multidisciplinary and intersectoral training programme (WP4) with a balanced combination of hands-on research training, intersectoral secondments, local courses and network-wide events on scientific and transferable skills, enabling future R&I collaborations. Hence, INSPIRE will equip the future generation of SP scientists with a wide range of scientific knowledge and the ability to adapt to a dynamic ever-changing industry.

Original text from CORDIS.

Participants

UNIVERSITEIT ANTWERPEN · AntwerpenCoordinatorBelgium
BOEHRINGER INGELHEIM PHARMA GMBH &CO KG · IngelheimGermany
INSTITUT NATIONAL DE RECHERCHE EN INFORMATIQUE ET AUTOMATIQUE · Le Chesnay CedexFrance
NCARDIA BV · LeidenNetherlands
NCARDIA SERVICES BV · LeidenNetherlands
NOTOCORD SYSTEMS · Le PecqFrance
THE UNIVERSITY OF NOTTINGHAM · NottinghamUnited Kingdom
TSE SYSTEMS GMBH · BerlinGermany
UCB BIOPHARMA · Bruxelles / BrusselBelgium
UNIVERSITEIT MAASTRICHT · MaastrichtNetherlands
WEIZMANN INSTITUTE OF SCIENCE · RehovotIsrael

INSPIRE · INnovation in Safety Pharmacology for Integrated cardiovascular safety assessment to REduce adverse events and late stage drug attrition.

Results in brief

INnovation in Safety Pharmacology for Integrated cardiovascular safety assessment to REduce adverse events and late stage drug attrition.

Project objective

Participants

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