DNDi: Drugs for Neglected Diseases Initiative

Drugs for Neglected Diseases (DNDi) is a not-for-profit organization founded in 2003 on the combined initiative of seven public and private institutions: Médecins Sans Frontières/Doctors Without Borders, the Indian Council for Medical Research, the Kenya Medical Research Institute, the Malaysian Ministry of Health, France’s Institut Pasteur, Brazil’s Oswaldo Cruz Foundation (Fiocruz), and the Special Program for Research and Training in Tropical Diseases of the World Health Organization.

A 120-strong team working out of its offices in Switzerland, Brazil, the Democratic Republic of the Congo, Kenya, India, Malaysia, the United States and Japan, coordinate a partnership network of around 600 engaged individuals who liaise with the public and private institutions involved in each project. Its mission is to discover and develop new treatments for neglected diseases and other poverty related conditions, and to ensure that patients in the most vulnerable countries enjoy equitable access to the results.

Since it was founded, DNDi has come up with six new treatments for forgotten patients by improving, reformulating or combining existing drugs. These include two treatments against malaria – ASAQ, developed in partnership with Sanofi, manufactured in Africa and distributed in 32 countries, and ASMQ, based on a technology transferred from Brazil to India; one to combat sleeping sickness – NECT, replacing previous toxic or more expensive treatments; a further two against visceral leishmaniasis – of shorter duration and now being distributed in East Africa and Asia; and a sixth against Chagas disease – a new pediatric dosage form of an existing treatment developed with a public laboratory in Brazil.

DNDi is currently promoting research in two other conditions: filarial parasitic worm diseases and pediatric HIV. It also has 30 projects at different stages of the development pipeline, 11 of which are totally new drug candidates. DNDi draws its funding in equal measure from public agents – governments and institutions – and the private sector – foundations, NGOs and other organizations.

Sleeping sickness, endemic in 36 African countries, causes tens of thousands of deaths a year. The last great epidemic was in the late 1990s with half a million people infected. The most widely employed treatment, a drug called melarsoprol, is so toxic it can kill. And, till recently, the only alternative was an extremely expensive, hard-to-administer compound whose manufacturer halted production at one point because it wasn’t making money. All that has now changed. Thanks to the efforts of the Drugs for Neglected Diseases Initiative (DNDi), a cheaper, more effective, more easily deliverable drug is now available; the first new sleeping sickness treatment in 25 years. The DNDi is this year’s recipient of the BBVA Foundation Frontiers of Knowledge Award in Development Cooperation.

This is not the DNDi’s only success. The organization and its partners have developed and distributed, “new effective and affordable treatments for poverty related diseases including Chagas disease, sleeping sickness, malaria and leishmaniasis affecting the world’s most vulnerable populations,” according to the award citation. “DNDi,” it goes on to say, “represents an institutional model of good practice, translating scientific research to development cooperation through knowledge management and the delivery of results to disadvantaged populations suffering from neglected diseases.”

The World Health Organization (WHO) has classed 17 diseases to the “neglected” bracket, because they are not in the main sights of pharmaceutical and biomedical research. These conditions are reckoned to account for 90% of the global disease burden – affecting over one billion people worldwide, half of them children – but attract only 10% of health research expenditure. The result is that of the 1,556 new drugs approved between 1975 and 2004, only 21 – a bare 1.3% – had been developed specifically for tropical diseases, including malaria and tuberculosis.

All this adds up to an economic as well as a health problem. As DNDi director Bernard Pécoul writes in his ‘“Manifesto” for Advancing the Control and Elimination of Neglected Tropical Diseases’, these conditions “are an important reason why the world’s poorest 1.4 billion people who live below the poverty line cannot escape destitution and despair; they are the most common infections of the world’s poorest people and the leading causes of chronic disability and poverty.” And this precisely is where the vicious circle kicks in, for a population doomed to perpetual misery is not an attractive market. “They are also diseases which kill or prevent their young sufferers from working, depriving the country of their potential,” Pécoul adds, “and that imposes a heavy economic burden. The victims cannot sustain a lucrative market so the private sector will not invest.”

It was to find a way out of this poverty-disease-poverty cycle that DNDi was founded as a non-profit organization in 2003 on the combined initiative of seven public and private institutions: Médecins Sans Frontières/Doctors Without Borders, the Indian Council for Medical Research, the Kenya Medical Research Institute, the Malaysian Ministry of Health, France’s Institut Pasteur, Brazil’s Oswaldo Cruz Foundation (Fiocruz), and the Special Program for Research and Training in Tropical Diseases of the World Health Organization. It now has a 120-strong team working out of its offices in Switzerland, Brazil, the Democratic Republic of the Congo, Kenya, India, Malaysia, the United States and Japan, and a partnership network of around 600 engaged individuals.

Its strategy is to detect the need for a particular treatment, then coordinate and synergize the efforts of public and private partners – including pharmaceutical companies – in its production and distribution, under strict quality standards, while working to relocate research and development capacity to the countries affected. The aim, ultimately, is to obtain cheap, effective, short-course treatments that are easy to administer, thereby facilitating compliance, with maximum attention to patient safety.

In sleeping sickness, for instance, the safest, most effective drug, until DNDi came on the scene, had to be injected every six hours over two weeks of hospitalization. The result was that many countries, put off by the cost, continued to rely on the highly dangerous melarsoprol. So the arrival of the new medicine in 2009 marked “a huge change,” Pécoul recalls. “I spent over 20 years with Médecins Sans Frontières, and it was tough walking into a hospital and knowing that the drug in use – an arsenic derivative – was so toxic that it killed 5 percent of the patients it was supposed to cure. But we had no alternative because the disease killed 100 percent.”

Besides this new drug, DNDi has come up with five treatments for forgotten patients that improve on existing drugs. These include two treatments against malaria – ASAQ, developed in partnership with Sanofi, manufactured in Africa and distributed in 32 countries, and ASMQ, based on a technology transferred from Brazil to India; a further two against leishmaniasis; and a sixth against Chagas disease – a new pediatric dosage form of an existing treatment developed with a public laboratory in Brazil.

The organization now has its sights on filarial parasitic worm diseases and pediatric HIV, and has a further 30 projects in the pipeline, eleven of which are new drug candidates. “We have signed contracts with a good number of pharma companies, some of them at quite early drug development stages,” Pécoul informs. “They know that they’re not going to make a profit, but the projects are supported by the people in their own teams and they are also aware that the countries affected are the market of the future.” Among DNDi’s partners is the Spanish plant of pharmaceutical giant GSK, which concentrates on global health priorities.

Neglected tropical diseases affect the poorest among the poor, “without political or economic power.” Their health, however, is an indicator of our own, Bernard Pécoul reminds us. And he illustrates his point with the words of Mahatma Gandhi: “A civilization is to be judged by how it treats its minorities.”