More creative thinking needed on drug R&D

Trypanosome parasite among red blood cells Copyright: University of Glasgow

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Proposals for a global treaty to boost research and development for neglected diseases by sidelining large pharmaceutical companies may appear utopian. But they highlight the urgent need for new ways of producing the medicines needed by the poor.

For every headline-hitting disease such as SARS and bird flu, there are dozens that rarely make the news but which threaten the populations of developing countries daily, infecting and killing millions because little research is done into ways to halt them.

Globally speaking, investment in health-related research and development (R&D) is higher than ever; annual spending is estimated to have risen from US$85 billion in 1998 to US$106 billion in 2001. But diseases affecting the developing world see relatively little of this money, partly because of the lack of commercial incentives for pharmaceutical companies to invest in an area that does not offer substantial profits. According to the Global Forum for Health Research, for example, despite several years of lobbying, only ten per cent of the resources is spent on research into the problems that afflict 90 per cent of the world’s population.

In the commercial world, one strong incentive for drug development is the ability to patent — and thus hold the intellectual property rights to – a new product. The World Trade Organization’s TRIPS (trade-related aspects of international property rights) agreement, which all member countries must sign up to, requires governments to provide patent protection for new inventions such as drugs for at least 20 years.

In principle, after this time a previously-patented drug could be produced by other companies as a ‘generic’ — or non-brand name drug — that sells for a fraction of the price of its brand name equivalent. In practice, governments often offer patent extensions on lucrative drugs to large pharmaceutical companies to encourage them to invest in R&D into another drug (whose patent is also likely to be extended).

This is among the reasons why, during the past 30 years, just one per cent of new compounds marketed have been for developing world diseases. And even within these, research priorities (and funding) are skewed towards HIV/AIDS, malaria and tuberculosis. One reason for this is that such diseases have a crossover with the developed world — for example, the travellers’ market for malaria — thus ensuring a market from which to recoup costs. In contrast, diseases such as Chagas disease, which kills 45,000 a year in Latin America, and visceral leishmaniasis, which kills 200,000 a year, receive little global attention, even within research priorities on developing world diseases.

Furthermore, under the current system, the key role played by patents and patent production has led to a proliferation of patentable ‘me-too’ drugs (that mimic existing ones and provide little if any new therapeutic value). As a result, the role of the patent system in boosting innovation has evolved into merely encouraging imitation; in 2002, ‘me-too’ drugs accounted for a staggering 92 per cent of medicines approved by the US Food and Drug Administration (FDA).

A new global R&D treaty

All this has put the issue of patents under the spotlight, and made it a central focus of efforts to boost research into neglected diseases. Some campaigns, such as the Drugs for Neglected Diseases Initiative, and the non-profit pharmaceutical Institute for OneWorld Health, seek to do this directly. But many believe that more substantial changes (including a radical rethink to the whole concept of patents) are needed to stimulate R&D for non-commercial diseases.

Two such individuals are Jamie Love of the Consumer Project on Technology, a non-governmental organisation focused on intellectual property issues relating to healthcare, which is based in Washington DC, United States, and Tim Hubbard of UK-based Sanger Institute in Cambridge, United Kingdom, who believe they have come up with an alternative to the "policy straitjacket" of TRIPS.

Their solution is to propose a novel treaty that would centre on requiring countries to commit themselves to making minimum levels of investment in R&D, based on their national income. Flexibility would be allowed in meeting such obligations. For example, it could be achieve through directly funding R&D projects (as the US National Institutes of Health does), by buying drugs at high costs, by creating innovation fund prizes, by setting up public-private partnerships, or by extending tax credits for companies that invest in R&D.

As with the terms of Kyoto Protocol that sets out ways of reducing global warming, countries would also be able to redeem ‘credits’ against their funding commitments by providing services. These could include technology transfer, R&D for neglected diseases, and the creation of ‘open-access’ medical databases.

As an example of such an innovation-focused award, the two campaigners point to the proposed US Medical Innovation Prize Fund, which is currently being considered by the US Congress, which proposes allocating 0.5 per cent of US gross domestic product for such incentives. Under this scheme, once the FDA approved a drug it would immediately become a generic — in other words it could be copied and produced by anyone. The innovator would be rewarded from the prize fund (spread out over the first ten years of a medicine’s use) rather than by recouping costs through selling the drug at a high price. The amount of prize money awarded would also be linked to the relative therapeutic benefits of the new drug — drugs for neglected diseases that affect poor countries would be given a higher reward. Thus, ‘me-too’ medicines with little new therapeutic benefit would be less of an R&D priority.

Backlash from industry

Unsurprisingly, many see the proposed treaty as an attack on the international patent system, especially TRIPS. Its proponents deny that this is true. Instead, they say, the intention is to make global R&D more pluralist, so that countries – particularly (but not exclusively) in the developing world — have the possibility of adopting an alternative way of promoting pharmaceutical innovation to the patent system.

Nevertheless, the proposal clearly originates from growing dissatisfaction with the constraints of the patent system, and its apparent failure to create adequate incentives for research into diseases of the poor. More than 160 public-sector scientists, including public health experts, economists and representatives of non-governmental organisations, have given it their support. And this public sector focus will inevitably be viewed as a strong critique of the pharmaceutical industry.

Equally unsurprising has been the fierce opposition that the proposals have drawn from the private sector. In particular, the International Federation of Pharmaceutical Manufacturers and Associations has rejected the treaty outright. Last month, the federation’s director-general Harvey Bale labelled the treaty’s proponents "anti-innovation activists", and said that they needed to acknowledge that 90 per cent of medicines on the World Health Organization’s (WHO’s) essential drug list were developed under the patent system.

Industry representatives also argue that, in building strategies for combating neglected diseases, there is currently too much of a focus on developing new drugs. In particular, they point out that infrastructure — such as effective healthcare and good transport links — in regions such as Africa is often weak. And strengthening this infrastructure, they say, is the task of the governments of developing countries themselves; its absence is not something for which the industry should be blamed.

Disagreement between the two sides has surfaced in a WHO online discussion forum, which has seen much heated debate between several of the players involved. In contributions to this forum, Love has pointed out that the public sector has played a major — and sometimes unrecognised — role in carrying out the research that eventually led to drugs for which pharmaceutical companies have subsequently filed patents. Trevor Jones, himself formerly the R&D director for one such company, argued in response that despite the public sector input, the key discoveries leading to the drugs in question were made by the companies concerned (forming the basis on which they justified their claim to a patent).

Stimulating innovation

That the current system creates few incentives to develop drugs for neglected diseases is clear. Public-private partnerships, often kept afloat by donations from organisations such as the Bill and Melinda Gates Foundation, are making inroads into widening the drugs ‘pipeline’ of R&D for non-commercial diseases. But, with little government support, at least in their current form, these partnerships merely act as a small sideshow to the R&D system.

Other approaches are already being explored for stimulating R&D for developing world diseases. One strategy being closely examined is ‘advance purchase commitments’, under which countries would make sufficient advance promises to buy vaccines for such diseases to guarantee an adequate return on substantial investments in research.

Last November, for example, Britain’s finance minister Gordon Brown pledged millions of pounds toward buying up potential malaria vaccines in advance. But critics point out that such a strategy disproportionately favours large pharmaceutical companies over small ones or not-for-profit organisations, and could perpetuate the current problem of an overly narrow research focus.

The treaty being proposed by Love and Hubbard takes a radically different approach. It makes several valid points. Developing country governments should certainly feel a responsibility for investing in R&D, for setting research priorities (in terms of which diseases to address) and for ensuring that the poorest of its population have access to cheap and effective drugs.

Both the lack of innovation in R&D today and a situation in which pharmaceutical companies only invest in drugs for which they see a sizeable return has held back progress in neglected diseases for too long. Indeed, whether something is a good idea or not is no guarantee that it will be taken up.

Where next?

There is a general consensus that the imbalance between R&D investments for diseases affecting developed and developing countries needs to be tackled if we are to meet the Millennium Development Goals for diseases such as HIV/AIDS and malaria, and for reducing child mortality and improving maternal health.

In principle, the proposals from Love and Hubbard could represent a significant step in this direction. But at present, obtaining the backing of national governments seems a distant prospect. In particular, it is unlikely that the United States, one of the key players in global R&D and drug manufacture, which has a history of refusing to sign up to treaties — such as the Kyoto Protocol — that would restrict industry, would sign up to this new treaty.

Perhaps reflecting this lack of enthusiasm, the WHO has so far declined to comment on the proposals. Indeed they do not even feature on the agenda of this month’s meeting of the World Health Assembly — the WHO’s decision-making body. 

The main stumbling block remains the likely opposition of powerful pharmaceutical companies. And although many developing country governments agree that better access to effective drugs is key to improving health — and thus enabling individuals to climb out of poverty — few are likely to be prepared to do so at what the industry would argue will be a considerable cost to their own economies; the furthest they are likely to go is supporting efforts to combine private and public resources, rather than pitting them against each other.

The proposed treaty, with its suggested displacing of pharmaceutical companies from their dominance of R&D on new drugs, is therefore unlikely to win enough political support (at least in its current form) to become reality. But it has helped to focus the debate over how best to direct R&D efforts at fighting diseases that affect most of the world’s population.

And this debate has itself helped to increase awareness of the ways in which, under the current model of R&D, the diseases of the rich continue to claim the majority of global investment in health research, while the poor continue to die of diseases for which medicines are either non-existent or too expensive. This is something that governments need to take more seriously if they are truly committed to tackling world poverty.