One of the key challenges in drug development is improvement of patient safety: many drug side effects are not adequately predictable and often detected too late, when the risk for serious outcome is high. The scientists of the SAFE-T project are developing improved tools for prediction, detection, and monitoring of drug-induced injuries to the kidney, the liver, and the vascular system, using markers in patients’ blood and/or urine.
More than 140 participants contribute to the consortium, coming from 20 partners overall: eleven pharmaceutical companies, five academic centres, and four small to medium sized enterprises. The consortium will focus on measuring sets of safety biomarkers across a variety of patient populations in order to define background variability, response to specific organ injury, and biomarker profiles under different disease conditions. The ultimate goal is to identify for each of the three organ toxicities a set of biomarkers more specific, more sensitive and more predictive than currently available ones, and to gain regulatory acceptance for routine use of these biomarkers in drug development.
To achieve that goal, the consortium is working in close collaboration with the regulatory agencies in Europe and the US, and is establishing links to other consortia and research groups to utilize synergies and maximize output. Samples collected by the consortium will be anonymized and kept in a centralized biobank; data from biomarker measurements will be stored in a dedicated database that will be maintained beyond the five year project lifetime to enable further research. After completion of the project, the thoroughly qualified safety biomarkers will help to significantly improve patient safety and reduce safety related attrition in drug development.
Achievements & News
IMI’s SAFE-T project enters formal collaboration with C-Path safety project
IMI’s SAFE-T project and the Predictive Safety Testing Consortium (PSTC) managed by the Critical Path Institute (C-Path) have formalised their collaboration through a legal agreement which will enable them to share research and regulatory strategies. ###
Both PSTC and SAFE-T are working on the development of new biomarkers to improve our ability to predict, diagnose, and monitor drug-induced injury to the liver, kidney, and vascular system. SAFE-T and PSTC have already been collaborating informally for some time. Increased collaboration between the two research consortia will be mutually beneficial and improve results for both projects. In particular, this agreement defines the framework for enhanced collaboration and exchange of information.
Benefits resulting from the collaboration between SAFE-T and PSTC will include reducing the cost of research while boosting efficiency; maximising the strengths of both projects; increasing communication with regulatory bodies and the projects’ scientific influence; the creation of a dataset with wide dissemination possibilities, and higher chances of the application of safer biomarkers.
- Read the press release
Smart SAFE-T strategy spots drug-induced liver injury
IMI project SAFE-T has devised a simple strategy that is able to identify patients with drug-induced liver injury before serious damage has occurred.###Writing in the journal PLoS ONE, the project team points out that 1 in 100 hospitalised patients experience liver injury as a result of an adverse drug reaction, but many cases are missed, especially in non-hepatology departments. The SAFE-T scientists used a common indicator of liver damage, namely alanine aminotransferase (ALT) levels. Using the SAFE-T strategy, all patients with ALT levels three times higher than the top end of the ‘normal’ range were referred to an experienced hepatologist. The SAFE-T strategy was compared to the hospital’s standard strategy, in which non-hepatologists refer suspected cases of drug induced liver injury (DILI) to experts. The results show that the SAFE-T strategy is much more sensitive, picking up 12 times more cases than the standard strategy and detecting cases of DILI while they are still in the earlier stages. ‘These results therefore strongly suggest that the centralized [SAFE-T] method could prevent very severe complications,’ the researchers write.
Major kidney ‘SAFE-T’ studies get underway
The IMI project SAFE-T has enrolled the first patients into 4 major studies that aim to boost scientists’ ability to determine whether or not a potential drug will be toxic to the kidney.###Drug-induced kidney injury is a serious problem in drug development and the treatment of patients. All too often, currently-used tests only detect kidney damage when it is already irreversible. The new SAFE-T studies aim to assess the potential of biological markers (biomarkers) that could allow doctors and researchers to detect kidney damage while it is still in the early stages. People participating in the studies include patients treated with medicines known to be toxic to the kidney; people with kidney diseases; and kidney transplant recipients who take immunosuppressant drugs that could be harmful to the kidney. According to the team, putting together studies of this scale would not have been possible without intense interdisciplinary and cross-institutional collaboration. The first results from the studies are expected in six to nine months. In addition to drug-induced kidney injury, SAFE-T researchers are also working on improving tests to pick up on drug-induced liver and vascular problems. Large-scale studies in these areas have also been initiated by the consortium.
- Novartis Pharma AG, Basel, Switzerland
- Laboratorios Almirall S.A., BARCELONA, Spain
- Amgen, Bruxelles, Belgium
- AstraZeneca AB, Södertälje, Sweden
- Bayer Schering Pharma AG, Berlin, Germany
- Boehringer Ingelheim International GmbH, Ingelheim, Germany
- Eli Lilly And Company Limited, Basingstoke, UK
- GlaxoSmithKline Research and Development LTD, Brentford, UK
- Pfizer Limited, Sandwich, UK
- F. Hoffmann-La Roche AG, Basel, Switzerland
- Sanofi-Aventis Recherche & Developpement, Chilly Mazarin, France
Universities, Research Organisations, Public Bodies & Non-profit
- Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen, Reutlingen, Germany
- Charite - Universitaetsmedizin Berlin, Berlin, Germany
- Assistance Publique - Hopitaux De Paris, Paris, France
- Consorci Institut Català de Ciències Cardiovasculars, Barcelona, Spain
- The Foundation For Medical Research Infrastructural Development And Health Services, Tel Aviv, Israel
- Firalis S.A.S., Huningue, France
- Argutus Medical LTD, Dublin, Ireland
- EDI Experimentelle und Diagnostische Immunologie GmbH, Reutlingen, Germany
- Interface Europe, Bruxelles, Belgium
Facts & Figures
|IMI funding||13 901 971|
|EFPIA in kind||17 855 120|
|Other||4 113 964|
|Total cost||35 871 055|
Novartis Institutes for Biomedical Research
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