HEALTH

An unprecedented public-private partnership

Fewer than 6 % of molecules at the preclinical development stage (tested on animals or cell cultures) find their way, a decade later, into pharmacies. © Shutterstock
Fewer than 6 % of molecules at the preclinical development stage (tested on animals or cell cultures) find their way, a decade later, into pharmacies. © Shutterstock

A decade ago, 70% of new medicines came from Europe. Today the figure has fallen to 30%. To stem this worrying decline, the Commission and federation of pharmaceutical industries have decided to pool the research needed to speed up sector innovation.

Two figures sum up the structural difficulties of the pharmaceutical industry. Since 1995, expenditure on research and development in the sector has increased by 80 %. Yet at the same time the number of new medicines marketed has fallen by 40 %. “This fall is due to a combination of scientific, regulatory and economic factors,” says Arthur Higgins, President of the European Federation of Pharmaceutical Industries and Associations (EFPIA). “Our companies are working to meet these challenges but it is clear that their efforts alone will not be enough.” This is why the EFPIA welcomed with enthusiasm the idea launched by the European Commission in 2007 for a new form of public-private partnership to boost the declining competitiveness of Europe’s pharmaceutical industry.

The aim of this Innovative Medicines Initiative (IMI) is not to come up with new medicines but to develop the tools, methods and know-how to facilitate future innovation. The road from a promising molecule to a medicine is long and full of obstacles, with fewer than 6 % of molecules at the preclinical development stage – that is, being tested on animals or cell cultures – finding their way, a decade later, into a pharmacy. There are three main reasons for this low success rate: the discovery of unexpected toxicity during the preclinical trials; the appearance of undesirable side effects during the phase I clinical trials – designed, in accordance with the Hippocratic precept of primun non nocere, to establish tolerance to the medicine among healthy human subjects – and, finally, insufficient effectiveness on patients during phase II and III clinical trials.

A strategic agenda

For each of these obstacles, the IMI’s strategic research agenda identifies promising avenues for research. To improve the predictability of toxicity, there is a need to develop databases that make it possible to link the undesirable effect of a molecule to the detail of its chemical structure, or biological markers that reveal quickly any problem that would only be apparent clinically several years later. To better understand the possible effectiveness of a molecule in combating one of the IMI’s five priority illnesses – cancer and cerebral, metabolic, inflammatory and infectious diseases – it is vital to identify cell models for the illness that permit the in vitro testing of a molecule’s effect, this also making it possible to reduce the use of animal experimentation, a cause to which the Commission and the EFPIA are committed.

A brief look back over recent decades reveals what can be expected of this upstream research. In the early 1990s, 40 % of molecules were rejected along the way because the testing phase revealed they were blocked by the body’s protective barriers or degraded by the immune system. Today these problems of biodisponibility are the cause of just 10 % of rejections. This is due to the progress made in modelling that makes it possible to determine in advance whether or not a molecule will be able to reach its target organ.

An original structure

All the parties involved in the medicine chain were thus invited to take part in the IMI. In addition to around 2 100 EFPIA member companies, this included academic research centres, innovative small and medium-sized enterprises (SMEs), patients’ associations, hospitals and the government agencies that grant marketing authorisations. To enable such diverse institutions to work together, an original legal structure was needed: the Joint Technological Initiative.

This Joint Technological Initiative is co-piloted by the Commission and the EFPIA, each injecting a billion euros into the IMI during the 2008- 2013 period. “The Commission is responsible for setting up and launching the IMI joint undertaking until it acquires the operational capacity needed to implement its own budget, which is planned for the third quarter of 2009,” explains Alain Van Vossel, IMI interim executive director. The two institutions are jointly represented on the Governing Board that manages the IMI and that is responsible for issuing calls for proposals. The latter are structured around four strategic pillars: forecasting the toxicity of molecules, predicting their effectiveness, improving knowledge management – in particular through the databases – and developing training of the highly skilled workforce needed by an industry that employs 500 000 people in Europe.

A unique procedure

To understand what is unique about the IMI you have to look at the original procedure for the calls for proposals. Only consortiums of public research institutes and innovative SMEs can respond and not companies seeking to benefit from the creativity of their partners. Experts appointed by the Governing Board examine the proposals and the best are submitted to a group of EFPIA companies interested in the subject. A second consortium is then created that formulates a final proposal in which research producers and their potential users are closely involved. After a further evaluation it is then this consortium that receives IMI funding. So as not to distort competition through direct aid to companies, there is a strict separation between public funds allocated by the Commission – which goes to public research bodies and innovative SMEs only – and private money from the EFPIA companies in the form of equipment, personnel and infrastructure.

Setting up projects supported by the IMI also required an imaginative legal approach to resolve the delicate question of the intellectual ownership of the research results. This was essential in persuading normally competing companies to pool their efforts. It was thus necessary to refine the legal notion of the research ‘background’ of Seventh Framework Programme projects to support the use of highly confidential information that the companies make available to their partners. It was also decided to allow each consortium a large measure of autonomy in determining the manner of sharing ownership of the research results.

Could this complex operating method in itself prove to be an obstacle to scientific creativity? It is too early to say. The IMI has already selected around 15 proposals submitted in response to its first call in May 2008, and the consortiums that will share the first €300 million should be set up in the summer of 2009. The two wise men charged with ensuring the transparency of expert appraisals and that there is no abuse on the part of the industrialists – which are both judge and party due to their participation on the IMI Governing Board – have already judged the organisation of the first call to be “well conceived and mature”. These are much appreciated words of encouragement for this unique and audacious public-private partnership.

Mikhaïl Stein



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The premises of the IMI

The reason European pharmaceutical companies have agreed to pool their pre-competitive research is that they realised the usefulness of such an approach with the Innovative Medicine for Europe (InnoMed) project, between 2005 and 2008. This consortium of 14 universities, 16 companies and 8 SMEs with a joint budget of €18 million set itself the goal of working together on two subjects: the description of biomarkers making it possible to monitor the progress of Alzheimer’s disease in man and in animal models; and the creation of databases with a vast quantity of information on the toxicity of molecules generated using techniques originating in genome sequencing. It is the success of this initiative that convinced the Commission and the industry to act on a larger scale.

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www.innomed-addneuromed.com


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