Reinvigorating European R&D innovation

Despite its importance to Europe, there is a feeling that the pharma industry is not as innovative as it once was and has lost ground to foreign rivals. This shift has been exacerbated by ambivalent attitudes from regional governments towards the industry; on the one hand, governments value the industry's economic contribution and its role in providing medicines, but they are also preoccupied with the rising cost of healthcare. As a result, pharma companies are under pressure to reduce their product prices.

Faiz Kermani

European companies believe that government cost containment measures have damaged the region's competitiveness, and point to R&D investment figures as evidence. In 1990, pharmaceutical R&D investment in the US was less than in Europe; however, R&D investment in Europe now is only approximately 70% of the US figure.¹ Between 1990 and 2008, R&D investment in the US grew by 5.6 times compared with 3.5 times in Europe.¹ To compound the situation, Europe also faces competition from further afield because of the rapid growth in the research environment in emerging economies, such as China and India. The European Federation of Pharmaceutical Industry Associations (EFPIA) has expressed its concern that this trend has led to the closure of European R&D sites.

Government policies alone, however, cannot be blamed for the difficult R&D conditions. Because of the inherent risks of drug development, many companies have adopted a conservative attitude to using new technologies that may add extra risk to the process, but the steady decline in new drug output suggests that this cautious approach is undermining innovation. However, although there is recognition that bottlenecks exist in the current R&D process, few solutions have been found to ease them.

EFPIA's analysis of the period 2004 to 2008 shows that, while European companies have experienced a decline in new drug output, their US counterparts have become the world leading inventors of new molecules.¹ This trend is worrying — particularly as the US pharma industry has expressed frustration at its own low level of innovation!^2,3 Similarly, the emerging markets of China and India are also considered to be far from optimal environments for R&D.^4,5

The Innovative Medicines Initiative

Many in the industry believe that there is no reason why Europe should not be able to keep pace with the US, given the existence of highquality research resources. Many also believe that the way to reinvigorate Europe's R&D lies in a collaborative approach, featuring both public and private parties. This thinking has led to the development of the Innovative Medicines Initiative (IMI), a public–private partnership designed by the European Commission (EC) and EFPIA, to find clear, practical paths to accelerating drug development and stimulate regional R&D.⁶ The initiative's Strategic Research Agenda will centre on addressing the problems identified with regional R&D by fostering collaboration across the region. This cooperative approach should reduce the risks for all those involved — particularly small companies.

The IMI's governing body is composed of ten board members — five from EFPIA and five from the EC, representing the European community. Although the IMI does not have a specific membership structure, it has a pan-European focus, with stakeholders across the region being eligible to participate in research. Once a year, the IMI also holds a stakeholder forum to disseminate information on activities and give participants the opportunity to provide input on the future direction of the organisation. In addition, the IMI holds consultative workshops with work through associations that represent participants concerned; for example, to better serve small companies, the IMI has said it will work with the European Biopharmaceutical Enterprises and EuropaBio.

The operation of the IMI is similar to that of a nonprofit organisation, with research grants being awarded to European public–private collaborations. While public money will be used to fund academic and patient participation and support SMEs, large biopharmaceutical companies will fund their own contributions.

The IMI has already identified the R&D bottlenecks as predicting safety, predicting efficacy, bridging gaps in knowledge management, and bridging gaps in education and training. From data collected, it was found that the likelihood of a drug candidate reaching the market was <6%.⁶ The most common factors for failure were lack of efficacy (25%), clinical safety concerns (12%) and toxicological findings in preclinical evaluation (20%).⁶ The best way to avoid these problems is to predict failure at the earliest stage possible in the R&D process, which necessitates placing greater importance on predictability and not becoming too dependent on promising preclinical data.

Between 1990 and 2001, predictability in the R&D process was enhanced through the development of drug metabolism studies. With time, invitro absorption and metabolism screens were validated by correlation with clinical data. The IMI aims to achieve similar clinical correlations for the factors that have been identified as the major causes of attrition. To do this, it is supporting panEuropean public and private sector collaborations so the research is not focused on products themselves, but generates tools, information and data that can be used by all companies. In this way, it is hoped that companies will be not be averse to their competitors having equal access to the results, as they stand to benefit from the outputs and sensitive product data are not being shared.

A European strategic research agenda

In 2004, the EC organised an initial consultation of stakeholders in Brussels (Belgium) where the need for better information exchange between those involved in European R&D was identified. A preliminary list of research issues to be addressed was also agreed upon. Following this initial consultation, the EC and EFPIA organised a series of workshops to further define the IMI's Strategic Research Agenda. As such, the agenda has evolved to include recommendations for the entire R&D process, as well as additional areas such as pharmacovigilance. Targeting all of these areas for improvement is a highly ambitious exercise, but those behind the IMI believe that the collaborative approach is why the initiative stands to succeed where others have failed.

To maintain control over work in these diverse fields, the Strategic Research Agenda has been organised around four strategic areas or 'four pillars' (Table 1). A total of 38 multidisciplinary recommendations, involving a combination of both new and traditional scientific approaches, have already been developed based around these four pillars.

Table 1: The IMI Strategic Research Agenda.

Despite the fourpillar structure, those behind the IMI are anxious to avoid a "silo mentality" and have stressed the interrelationships between the different strategic areas. By coordinating the activities within each of the four pillars, the IMI hopes to create synergies from the new scientific knowledge gained. For example, Pillar IV, concerning education and training, is considered essential for the safety and efficacy pillars to be supported effectively.

The IMI has stated that all "foreground" research will be owned by the participants concerned and that they may access and commercialise the outputs. However, it does not want to restrict access to this work and will seek to make it available to third parties as appropriate ("under fair and reasonable terms"). Although bigger companies might be able to make use of the information generated from the IMI projects without necessarily being involved, they probably stand to gain more from participating. Collaboration would allow the bigger players to contribute to the scientific direction of the IMI projects, which would allow them to better determine how to use the information generated. This set up will probably be too enticing for the major companies to pass up on. Besides, if they don't participate then there is always a chance that their rivals will.

Outlook

The European pharmaceutical industry has long expressed its concern that the R&D environment in which it operates is less than ideal; however, the factors hampering innovation cannot be solely attributed to government policies, such as cost-containment initiatives. If European companies want to justify the high prices of their drugs and have a valid argument to counter cost-containment policies, they will need to make major medical advances — a continuing output of 'me-too' products and line extensions will do nothing to help the industry's case.

With the launch of the IMI, it looks as if many of the factors holding back innovation will finally be addressed. Those behind the initiative have emphasised the project's urgency, particularly as the US already has its own initiatives to promote innovation, such as the US Biomarker Consortium and initiatives under the FDA's Critical Path. What stakeholders will be looking for is a deadline for the IMI to deliver upon its promises. However, it will be up to the companies themselves to make the most of its outputs.

The author says...

• The European pharma industry has lost ground to foreign rivals — R&D investment in Europe is now only approximately 70% that of the US.

• To reinvigorate R&D, the Innovative Medicines Initiative (IMI) has been established to find clear, practical paths to accelerating drug development and stimulating regional R&D.

• The IMI will help to foster collaborations across the region, which should reduce the development risks for all those involved.

• The IMI's Strategic Research Agenda is organised around four areas: predictability of safety evaluation, predictability of efficacy evaluation, knowledge management, and education and training.

References

1. EFPIA, "The pharmaceutical industry in Europe: key facts and figures" (2008). www.efpia.org

2. Pharmaceutical-Technology, "Lilly CEO Criticises Lack of Biopharma Innovation" (2009). www.pharmaceutical-technology.com

3. The In Vivio Blog, "Innovation Is the Pharmaceutical Industry's Only Salvation" (2009) http://invivoblog.blogspot.com

4. Private Sector Roles in Global Public Health, "Shaping incentives for private sector biotech innovation in China" (2009). http://stanford.edu

5. RNCOS, Indian Pharma to Get Rs 2,500 Crore Investment (2009). .www.rncos.com

6. IMI, The Innovative Medicines Initiative: Scientific Priorities/Research Agenda (2009). www.imi-europe.org