IMI – Innovative Medicines Initiative
SAFE-T Project: researchers search for biomarkers to improve the early detection of drug-induced organ damage
Pharmaceutical researchers and physicians want to be sure that a drug gives the patient the best help possible. And patients must be able to rely on the pharmaceutical industry and physicians having – and using – the necessary information to ensure that they get the most effective and safest treatment. The development of a new drug takes ten to twelve years and costs about €800 million. It is essential for a research-based pharmaceutical company to know as early as possible whether a new active ingredient can cause serious side effects – such as organ damage – in certain patients.
It is therefore in everyone's interest to be able to make predictions on possible side effects as early as possible. Biomarkers in the blood, urine or tissue samples are excellent indicators in this context.
Biomarkers as an early indicator of possible side effects
| Background IMI |
|
The Innovative Medicines Initiative (IMI) was set up jointly in 2008 by the European Commission and the European Federation of Pharmaceutical Industries and Associations (EFPIA) to accelerate the research and development of new and better drugs in Europe through cooperation between the pharmaceutical industry, academic research, hospitals, regulatory authorities and patient organizations.
|
A biomarker might be a known blood parameter (such as the level of glucose or lipids) that is significantly altered by the drug. Or it might be a hardly noticed or not-yet-identified protein that appears as a result of the damage. At present there are very few biomarkers that have been clinically tested as early indicators.
To identify such a biomarker, it is important to be certain that it really was triggered by administration of the active ingredient and not, for example, by a disease. "This requires comprehensive studies, for example both on kidney patients and on other patients with healthy kidneys," says Dr. Matthias Gottwald from Bayer Schering Pharma. He is currently helping to set up the IMI organization in Brussels as a member of the IMI Governance Task Force of the European Federation of Pharmaceutical Industries and Associations (EFPIA). For, if the markers also occur in healthy people, they are 'interfering signals' – caused, for example, by certain underlying diseases – which make it impossible to recognize the so-called safety biomarker. Similarly, the validity of the marker must not be affected by lifestyle factors (diet, alcohol or tobacco consumption) or the patient's age and gender.
Using biomarkers to improve treatment options
| Aims of IMI |
|
The IMI's aim is to dismantle barriers to innovation in order to make the development of new therapies faster and more efficient.
This is to be achieved by:
- by developing methods and technologies that more precisely predict the safety and efficacy of new active ingredients,
- by means of knowledge management, and
- by promoting advanced and further training.
The IMI has been equipped with a research budget of €2 billion over a six-year period, half of which comes from the EU Commission and half from the pharmaceutical industry.
|
The identification of biomarkers involves the respective development of robust and high-throughput test systems (assays), so that marker identification can be implemented quickly, reliably and cost-effectively and quickly find its way into hospitals and doctors' practices. "Our aim is to ensure that validated markers are incorporated into the treatment guidelines," says Matthias Gottwald.
A physician can then use biomarkers to determine which drug is the most suitable for his/her patient in order to maximize safety.
Europe-wide search for new biomarkers: the SAFE-T project
The aim of the IMI's SAFE-T project (Qualification of Translational Safety Biomarkers) is to identify new, sensitive biomarkers that help reliably predict a drug's safety as early as possible, i.e. when the trials of a new active ingredient are just beginning. The focus is on biomarkers that provide unequivocal evidence of kidney, liver or vascular damage.
A further aim is to then have these biomarkers included as a criterion in treatment guidelines by the EMEA (European Medicines Agency). EMEA representatives have therefore been integrated into the project from the outset.
Bayer Schering Pharma's involvement in SAFE-T
Bayer Schering Pharma is taking part in two SAFE-T sub-projects. One area our researchers are concentrating on is kidney damage triggered by active ingredients. Although such damage can be created in animals under controlled laboratory conditions, corresponding observations in humans are extremely difficult.
Severe organ damage caused by drugs are rare and often only occur as a result of drug abuse (a typical case is the abuse of painkillers). Only a few such cases a year are comprehensively documented worldwide. "It's therefore a great advantage that our work is coordinated Europe-wide, because this enables us to pool these cases for the first time," Gottwald emphasizes.
Our researchers are also working on the related bio-banking project. Patient samples are crucial for identifying and validating new biomarkers. This also involves concrete logistical questions: How are clinical samples archived and comprehensively documented? How are the partners all over Europe informed quickly about which test is available for which purpose and from which partner? 'Double inventions' are avoided because the partners share their knowledge on all available measurements and the methods used.
Extensive partnership for more security
SAFE-T is the IMI's biggest project so far with a budget of €33 million. The participants on the industry side are Astra-Zeneca, Boehringer Ingelheim, Eli-Lilly, Amgen, Glaxo-Smith-Kline, Pfizer, Hoffmann-La Roche, Sanofi-Aventis, Novartis, and Bayer Schering Pharma.
The academic partners include the Charité (university hospital) in Berlin, the Natural and Medical Science Institute at the University of Tübingen (NMI), the AHPA hospital consortium (Paris), the Barcelona Cardiovascular Research Center, the Tel Aviv Medical Center, and the Argutus and Viralis biotech companies.
