For the past decade the pharmaceutical industry has struggled with the impact of fiscal pressures, cost containment by payers, increased R&D costs coupled with an overall decline in R&D productivity and ever greater regulatory hurdles. There is therefore an urgent need to increase the `probability of success' of R&D projects.
Figures from McKinsey show that 89 per cent of molecules in development fail, 42 per cent of phase III trials fail and 70 per cent of launched products do not recoup their initial investment.
As a first step it is vital that companies have a better disease understanding and for many that means greater investment in applied genetics and fundamental biology research.
The next stage is to turn this understanding into tools and processes to accelerate projects that can deliver superior value. At the same time unproductive projects need to be terminated faster.
The key to achieving both the first and second stages is long-term networked collaboration between academic researchers, clinicians, pharmaceutical and biotechnology companies.
Isaac T Kohlberg, senior associate provost and chief technology development officer from Harvard University, said: “We encourage and welcome collaborations with pharmaceutical companies that push the boundaries of translational science and advance basic research discoveries from the lab to the clinic, thus working together to progress the science beyond the initial research that brought the company and scientist together.”
A two-way communication between academia and pharma companies throughout the research phases and product development should be the goal, as both parties can learn from each other, enabling longer term ideas and developments to flourish.
The importance of translational research in product development was suggested as the way forward by Ismail Kola and John Landis in Nature Reviews back in 2004.
“Bringing the right drugs to the right patients in the shortest time frame is the primary mission of translational medicine – we need to rapidly establish if the drug sufficiently interacts with the target in the relevant tissue and if the target is critical for the disease process,” stated Ismail Kola, executive vice president of UCB Pharma and president of UCB New Medicines.
But how much attention have pharma companies paid to this approach during the intervening eight years?
Some pharma companies are forward-thinking in their approach to academic/research interaction, while others need to consider what can be achieved through collaboration even at an early stage of research.
Translational research can ensure a higher probability of success prior to the molecule's entry into large and expensive mid- and late-stage clinical development. By conducting small but robust studies with clear biomarkers, companies can make data-driven 'go/no go' decisions based on changes to those biomarkers. For example, a study in 50 patients could determine if the candidate therapeutic sufficiently modulated the target to a level where researchers would be confident that the outcome would be a meaningfully differentiated product.
But even before the human experimentation stage, translational medicine can have a role. If scientists can engineer preclinical models that better mimic the human condition, especially via a genetic mutation that is well understood, early indications of the value of the research can be assessed.
“At its best, translational research enables ground-breaking research to evolve more rapidly from the laboratory to the patient and it's an area of strength for British science,” asserts Mark Samuels, managing director of the National Institute for Health Research's Office for Clinical Research Infrastructure.
What is it?
Translational research is a way of conducting scientific research 'from bench to bedside' and also 'from bedside to bench', making the results applicable to the relevant patient population.
Why is it important?
It translates research findings more quickly and efficiently into medical practice and, thus, indicates meaningful health outcomes, whether those are physical, mental, or social.
How has its role changed/developed in recent times?
Governments and pharma have spent vast amounts on basic research but achieved less-than-anticipated return on investment. Translational research is seen as the key, missing component.
Why is it coming to the fore?
Forward-thinking pharma companies recognise that action needs to be taken to improve R&D success rates. Governments too are aware of competition from the US and China and are supporting incentive programmes for public-private collaboration.
A good example of this 'bench to bedside' approach has been the translational research into the protein sclerostin, mutations of which are associated with the syndrome sclerosteosis. This is a rare inherited genetic disorder in which there is an excessive formation of normal quality bone when sclerostin is completely absent from birth. Heterozygous carriers of sclerosteosis do not have any of the bone complications due to bone overgrowth, but do have bone mineral density values that are consistently higher than those of normal, healthy individuals. Through foundations built on translational research, a sclerostin antibody for the treatment of low bone mass disorders is being developed.
In addition to the goal of improving patients' lives, another motivator for improving R&D success rates is financial. Pharma needs to see a better return on its investment in R&D, while at the same time operating in a research market that is better supported by public funds.
The EU invests nearly a third less in R&D than the US, at 1.9 per cent of its GDP compared with 2.8 per cent in the US. It is also losing competitiveness to emerging markets such as China, which is now the third country in the world for primary research publications.
At the same time there is a huge unmet medical need in Europe, with too many patients suffering from severe diseases. Plus, people are living longer. Currently for every elderly person in the EU there are four working-age citizens. By 2050 that ratio will be halved.
The catalyst may come from the Innovative Medicines Initiative (IMI), a public-private partnership between the EU and the European Federation of Pharmaceutical Industries and Associations (EFPIA), which promotes innovation through collaboration. Its aim is to make drug development more efficient and bring safer and better medicines to patients more quickly. [Editor's note: See our interview with IMI executive director Michel Goldman].
So far, 225 different research groups from 23 major pharmaceutical companies are collaborating with 298 academic teams, 47 small and medium-sized companies, 11 patient organisations and the European Medicines Agency.
But Ismail Kola warns that private, usually pharma, money alone is not enough to finance such initiatives: “It is important that governments across Europe continue to support academic life science departments. As long as these academic institutions flourish, there will be scientists at the universities for pharma to work with. If, however, government funding diminishes and scientists leave academia to seek alternative careers, the quality and choice of researchers will not be available and pharma will not seek to work with them. It's a continuous loop in which every stakeholder – academia, pharma and government – must play its part.”
At the end of 2011 the UK government launched the first two of the National Institute for Health Research (NIHR) Translational Research Partnerships (TRPs) for early-stage research in inflammatory respiratory disease and joint and related inflammatory diseases.
The inaugural TRPs include input from NHS trusts and universities/colleges, with 26 participating organisations in the Inflammatory Respiratory Disease Partnership (addressing conditions such as asthma, allergy, chronic obstructive pulmonary disease, cystic fibrosis, acute lung injury and respiratory infection) and 27 in the Joint and Related Inflammatory Diseases Partnership (tackling conditions such as rheumatoid arthritis, osteoarthritis and synovitis).
Access to the Partnerships is via the NIHR Office for Clinical Research Infrastructure, providing an easy and consistent point of entry for industry.
The participating universities and NHS trusts have also all signed one legal agreement to work together using a single set of business processes that will encourage collaboration with industry on translational research.
In a recent press release from the Department of Health, Sir John Bell, president of the Academy of Medical Sciences and regius professor of medicine at Oxford University, said that the TRPs “demonstrate that the NHS is ready and willing to work with industry in early development, the most difficult but most important part of the development pathway.”
Translational research enables government health departments, university clinical researchers and pharmaceutical companies to work closely together, combining resources and expertise to give new therapies the best possible chance of rapidly advancing into treatments.
However, it will only work effectively as long as all sides invest both time and money in the process. In particular European governments must continue to invest in life sciences departments within universities to ensure that high-calibre researchers can be attracted and retained, creating a high value resource for collaboration and innovation.
Roger Palframan is global project leader at UCB Pharma