Tropical diseases such as chloroquine-resistant malaria, leishmaniasis, lymphatic filariasis, Chagas disease, human African trypanosomiasis, dengue fever and schistosomiasis continue to cause significant morbidity and mortality. With few new treatments that tend to be unaffordable and poorly adapted to the field, physicians are forced to use old tropical medicines that are increasingly ineffective due to inevitable drug resistance. Together with tuberculosis and HIV/AIDS, these disabling and/or life-threatening diseases represent an enduring unmet medical need and are collectively called “neglected diseases”.

Of the 1,556 new drugs approved between 1975 and 2004, only 21 (1.3%) were specifically developed for tropical diseases and tuberculosis, even though these diseases account for 11.4% of the global disease burden.

With exponential progress made in the basic knowledge of many infectious diseases, it is ironic that the drugs currently used to treat kinetoplastid diseases were discovered decades ago. With few exceptions, the wealth of basic research knowledge of these parasites is not being translated into practical applications.

In 1999, Médecins Sans Frontières, in response to the lack of drugs for neglected diseases, convened an interdisciplinary group of experts – the Drugs for Neglected Diseases Working Group – who proposed the Drugs for Neglected Diseases Initiative (DNDi) as a new approach to address this crisis, and DNDi was established in July 2003. In addition to MSF, DNDi’s founding members include five research institutions: the Kenya Medical Research Institute, the Indian Council of Medical Research, the Oswaldo Cruz Foundation in Brazil, the Ministry of Health in Malaysia, the Institut Pasteur. The TDR Special Programme for Research and Training in Tropical Diseases (UNICEF, UNDP, World Bank, WHO) acts as a permanent observer to the initiative.

Why are some diseases more neglected than others?

Market failure: Drug development has largely been confined to the research and development (R&D) based pharmaceutical industry, which has grown into one of the most prosperous industries by focusing on lucrative markets. The reliance on market-based incentives and commercial actors to make new medicines has transformed drugs into consumer goods and has skewed investment toward diseases and patients that guarantee significant financial returns. With North America, Europe and Japan accounting for 80% of the world pharmaceutical market yet only 15% of the world’s population, the health needs of the majority of the world’s population are being sidelined.

Publicly-financed research institutions are involved in the early-stage drug R&D, but the private commercial sector holds the expertise, infrastructure and management capacity to take early-stage findings through the drug development pipeline. Hence, while multimillion-dollar investments fund research aimed at developing highly profitable drugs for prosperous markets, drug R&D for neglected diseases is stifled as little knowledge or technology is transferred from the public to the private sector.

A distinction between “neglected” and “most neglected” diseases can be made (Figure 1). The World Pharmaceutical Market is made up predominantly of global diseases and lifestyle conditions such as male pattern baldness, obsessive shopping, stress and jet-lag, which represent a highly profitable market segment in wealthy countries, even thought these diseases are not purely disease based. Global diseases include cancer as well as cardiovascular, metabolic, bone and joint diseases; affect people around the world; and constitute the main focus of the R&D-based pharmaceutical industry. Neglected diseases such as malaria and tuberculosis primarily affect people in poor countries but secondarily affect people in industrialized countries (e.g. people who contract malaria while travelling). Therefore, a small market exists, as do some R&D efforts. Most neglected diseases include human African trypanosomiasis (also known as sleeping sickness), South American trypanosomiasis (also known as Chagas disease), Buruli ulcer, dengue fever, leishmaniasis, leprosy, lymphatic filariasis, and schistosomiasis. These diseases predominate in developing countries, where people are too poor to pay for any kind of treatment and do not represent a viable market. Therefore, these diseases fall outside the scope of the drug industry's R&D efforts.

Public policy failure: Market failure has been compounded by failure of public policy – both globally and within endemic countries – to ensure the development of drugs for neglected diseases. Industrialized countries who subsidize basic and discovery research at universities and public research institutes have developed a series of enabling incentives to foster private R&D investment that can transform scientific advances into medical products. Such incentives include the patent system and various forms of public purchasing to pay for health tools (e.g. national health care and insurance systems).

In neglected disease-endemic regions, the public sector has not adequately cultivated drug development expertise and capacity. In countries with drug R&D potential, governments lack financial resources and political will to invest in long-term health development. They have also failed to establish public policy incentives that foster viable domestic drug R&D industries.

This balance between public and private capacity, investments and interests has worked reasonably well to provide important health tools for populations in industrialized countries, but it has not been effective in providing new or adapted health tools for diseases occurring almost exclusively in the developing world.

In response to the public policy failure, DNDi launched a campaign in 2005 to wake up governments on health tools’ R&D for neglected diseases.

An Alternative Model in the New Millenium

In recent years, awareness of the lack of effective treatments for neglected diseases has been growing, and some novel approaches have emerged to stimulate R&D and to produce needs-adapted health tools. One such approach is that of product development partnerships that seek to foster R&D for neglected diseases by building partnerships - based on existing capacity, expertise and resources - in both the public and the private sector. Typically, these initiatives act as coordinators in setting a disease-specific R&D agenda and portfolio, raising funds, and managing R&D projects. Examples include the Medicines for Malaria Venture, the Global Alliance for TB Drug Development, the International Aids Vaccine Initiative, and the Foundation for Innovative Diagnostics.

As a product development partnership whose aim is to develop 6-8 new treatments for the most neglected diseases by 2014, DNDi currently includes in its R&D portfolio: 22 projects on visceral leishmaniasis, human African trypanosomiasis, Chagas disease, and malaria. DNDi does not conduct R&D to develop drugs by itself. Instead, DNDi capitalizes on existing, fragmented R&D capacity, especially in the developing world, and utilizing additional expertise as needed. This “virtual organization” model helps cut costs.

DNDi fosters collaboration both among developing countries and between developing and developed countries. Blending centralized management for a clear project-specific focus with decentralized operations that mimic modern drug companies, DNDi has built regional networks of scientists actively involved in the research of new drugs for neglected diseases in Asia, Africa and Latin America.

These regional networks, coordinated by DNDi regional liaison officers, are vital to the success of DNDi. Not only do they gather information on available regional expertise, capacity, and patients’ needs but also actively advocate for DNDi, encourage scientists to submit proposals to DNDi’s call for letters, and organize regional scientific meetings. DNDi currently has representatives in Brazil, Democratic Republic of Congo, Kenya, India, Japan, and Malaysia and will have a representative office in the US by Q2 2007.

Public Leadership Needed for Success

Product development partnerships have become increasingly prominent in a field that had been largely deserted. Mainly supported by philanthropy, the major driver is the Bill and Melinda Gates Foundation. Growing investments from wealthy governments to support R&D for neglected diseases are still insufficient to provide a sustainable response that meets the needs of the most neglected. In the recent past, institutional financial support for R&D for neglected diseases (mainly the Big Three of HIV, TB, and malaria) has grown, but is still far from the requisite US$ 3 billion per year, as documented by the WHO’s Commission on Macroeconomics and Health in 2001.

To ensure that product development partnerships and other players deliver new drugs that could fundamentally change the way neglected diseases are treated, governments must support and facilitate translational research, support additional medicinal chemistry capacities through their own academic institutes, and define the most neglected diseases in their research priorities. To bring the best science for the most neglected, this public leadership is crucial.

*Bernard Pécoul has been Executive Officer of the Geneva-based Drug for Neglected Diseases Initiative (DNDi) since its inception in 2003. He is coordinating the entire research and development initiative and managing a team of project managers and scientists located in various parts of the world, in particular Asia, Africa and Latin America, who are working on DNDi projects. Contact: bpecoul@dndi.org, www.dndi.org.