MSF's Drugs for Neglected Diseases initiative (DNDi) will address what MSF-USA executive director Nicolas De Torrente called "a fundamental mismatch, expressed as millions of lives lost each year, between human needs and scientific innovation." Planning began in 1999, when MSF gathered international experts to identify contributing social, political, economic, and technical factors, and to suggest solutions. The March unveiling, in a packed auditorium at the Graduate Center of the City University of New York, attracted almost 400 people—an eclectic mix including government scientists from the United States and European Union, representatives of MSF and the World Health Organization (WHO), activists and health care workers, a brave few from the pharmaceutical industry, and interested others.
The challenge is clear. "Old drugs are becoming less effective, existing drugs aren't being made, and no new drugs are on the horizon," summed up James Orbinski, working group co-chair and a researcher at the Munk Centre of International Relations at the University of Toronto.
Defining the Problem
To assess Big Pharma's commitment to neglected diseases, in spring 2001 the DNDi working group and the Harvard School of Public Health surveyed 20 large pharmaceutical firms in the United States, Europe, and Japan. Of 11 responders, eight had done no research over the past year in tuberculosis, malaria, African sleeping sickness, leishmaniasis, or Chagas disease; seven spent less than 1% of their research and development budget on any of these disorders. In contrast, the Pharmaceutical Research and Manufacturers of America's New Medicines in Development survey3 found that, of 137 drugs in the pipeline to treat infectious or parasitic disease, one targeted sleeping sickness and one malaria. Yet eight drugs are in clinical trials for erectile dysfunction, seven for obesity, and four for sleep disorders. The most neglected diseases affect predominantly people in the southern hemisphere who do not contribute to the pharmaceutical market.
Torreele identified gaps in the drug pipeline that fuel the crisis. The most important gap is the first, between basic research and preclinical investigations, which coincides with the public-to-private sector transition, she said. Added Paris-based Yves Champey, director of the feasibility study for DNDi, "Public research is producing a wealth of new knowledge on the agents of parasitic diseases, but the ideas are not being developed into medicines. We need a means to deploy new knowledge."
The second gap is from preclinical work to clinical trials, which requires a strategic decision and commitment within a company. "If there is a candidate drug to treat Alzheimer's and one to treat African sleeping sickness, it is easy to understand which one will go on to be developed," Torreele said. The final gap arises between clinical research and delivery to patients. Said Navaratnam, "Sitting in New Jersey or Geneva and trying to understand the dynamics of an illness in Botswana is very difficult. We need to get development of drugs to the people right where they need it." And that's exactly what the DNDi will do.
Approaches to flag economic interest include the "pull" of higher royalties for neglected diseases, and the "push" of government subsidy of basic research in certain diseases. Increasingly, public-private partnerships, such as the collaboration among GlaxoSmithKline, the University of Liverpool, WHO, and the UK's Department for International Development, are working to find new treatments for multidrug-resistant malaria. David Brandling-Bennet, deputy director of the Pan American Health Organization of WHO, listed such partnerships working to target a half dozen neglected diseases.
Funding for the DNDi will come from what Orbinski called "charity replacing duty." It will rely mostly on fundraising, support of foundations such as the Pasteur Institute, and philanthropy. "DNDi is not a public-private partnership in the way it has been defined over the past few years, but a partnership for public response to the crisis of neglected disease. The partners will be close to the need, and they are willing and able to assume responsibility as part of their public duty. No pharmaceutical companies will be founding members, although DNDi can still have contracts with industry on focused projects," he explained.
This reliance on giving is necessary because many industrial and government efforts seem out of sync with reality. For example, five drug companies offered to cut HIV drug prices to MSF, but these costs are still three times Cipla's $350 yearly price tag. Navaratnam put this into a sobering perspective: "When someone's income is 10 cents a day, a medication reduced to $5 is still unaffordable." Varmus pointed out that the US government gives one-eighth of 1% of its gross national product (GNP) for the most neglected diseases, although that may change.
How Scientists Can Help
He concluded, "Advances in biology and medicine can and must be used to combat disease in the developing world." With the framework that the DNDi will provide, that hope is one giant step closer to reality.
1. D. J. Ncayiyana, "Africa can solve its own health problems," British Medical Journal, 324:688-9, March 23, 2002.
2. K. Wengelnik et al., "A class of potent antimalarials and their specific accumulation in infected erythrocytes," Science, 295:1311-4, Feb. 15, 2002.
4. G. Yamey, "US trade action threatens Brazilian AIDS programme," British Medical Journal, 322:383, 2001.
5. H. E. Kettler, R. Modi, "Building local research and development capacity for the prevention and cure of neglected diseases: the case of India," Bulletin of the World Health Organization, 79:742-7, 2001.
6. P. Jha et al., "Improving the health of the global poor," Science, 295:2036-9, March 15, 2002.