DNDi and New Drugs for Neglected Diseases

May 24, 2011

This article is part of the Spring 2011 issue of the MSF Alert newsletter.

Founded in 2003, the Drugs for Neglected Diseases initiative (DNDi) brings together the academic, medical, public health, and pharmaceutical worlds to create effective drugs to treat neglected diseases like Chagas disease, sleeping sickness, and visceral leishmaniasis. DNDi has developed an innovative not-for-profit model for drug research and development that is patient-centered and based on needs rather than profits. In just seven years, under the leadership of former General Director of MSF in France, Dr. Bernard Pecoul, DNDi has introduced four new treatments: two treatments for drug-resistant malaria that have already reached 80 million people; the first new treatment in 25 years for the advanced stage of sleeping sickness; and a new combination therapy for treatment of visceral leishmaniasis in Africa.

Rachel Cohen, the Regional Executive Director of DNDi’s North America office—and previously MSF’s Head of Mission in South Africa and Lesotho and US Director of MSF’s Campaign for Access to Essential Medicines—talks about DNDi’s current projects and goals.

How did DNDi get started?

DNDi shares the same roots as MSF’s Access to Essential Medicines Campaign: doctors and nurses who were increasingly frustrated by the lack of medicines and diagnostics to treat diseases patients present with in their clinics and hospitals.

At first, the Campaign focused on five main diseases: HIV/AIDS, tuberculosis, malaria, visceral leishmaniasis (or kala azar), and sleeping sickness (or Human African trypanosomiasis). But it became clear that for the most neglected diseases it was not a matter of advocating for reduced prices and overcoming patent barriers on existing drugs, as was the case with HIV/AIDS, but rather that safe, effective, and easy-to-use drugs didn’t exist. Existing drugs were either highly toxic or very difficult to administer—or both. The people suffering from neglected diseases in Africa, Asia, and Latin America were not an interesting enough market for a pharmaceutical industry that bases its success in large part on its ability to generate profits.

So in 2003 MSF brought together five prominent public sector research institutes—Brazil’s Oswaldo Cruz Foundation, the Indian Council for Medical Research, the Kenya Medical Research Institute, the Ministry of Health of Malaysia, and France’s Pasteur Institute—and the UNDP/World Bank/World Health Organization’s Special Program for Research and Training in Tropical Diseases to create DNDi.

Part of what’s so interesting is not just that we have created a successful nonprofit model for making lifesaving drugs for people who need them, but that we are strengthening research and development capacity in countries where these diseases are endemic. To date, DNDi has delivered four treatments and has five other projects in clinical development. And we’ve built the most robust pipeline that exists for the specific group of neglected diseases we focus on.

The World Health Organization lists 17 neglected diseases. Why does DNDi focus on three?

Quite simply because these are the most neglected and are fatal if left untreated. There were no adequate medicines or diagnostics, and they affect the poorest, most vulnerable communities.

Sleeping sickness, for example, is transmitted by the bite of the tsetse fly that puts victims into a coma before they die. It’s endemic in 36 African countries. For decades the most widely available treatment was melarsoprol, an arsenic-derivative that killed one in 20 patients. Eflornithine, a far more effective treatment, went out of production for a while because the producer could not make a profit.

DNDi decided to see whether using existing drugs in new combinations would improve treatment options—a short-term strategy that goes hand-in-hand with our longer-term strategy to look for new compounds. The result was NECT, a combination of nifurtimox and eflornithine, the first new treatment for sleeping sickness in 25 years. It reduces the number of intravenous infusions of eflornithine from 56 to 14 days and shortens hospitalization from 14 days to 10. NECT has been added to the WHO’s Essential Medicines List and is being used in 10 African countries right now.

How does DNDi go about its work?

Our approach is patient-centered. It’s not just a matter of finding a drug that works against a particular parasite but a matter of finding a less toxic, better tolerated, easy-to-take drug appropriate for poor women in rural areas, for example, or children. We bring together many different players, particularly from disease-endemic countries, in a process to create what we call “target product profiles.”

Take Chagas. It is endemic in the Americas, where 100 million people are at risk and 8 million are affected annually. Chagas is tough to diagnose. It’s transmitted by something called the kissing bug because its bite is so gentle that you don’t know it bit you. Some people live for years without showing symptoms. Then they can develop organ failure—usually the heart is most affected—but the disease goes undiagnosed. In the acute phase, one in 20 infected people die, primarily children. Current treatments—benznidazole and nifurtimox—only work for acute and early symptomatic Chagas. It takes 30 to 60 days to treat and is quite toxic. There’s no treatment for the chronic phase, and no pediatric formulation, despite the fact that children are the disease’s main victims in its early stages.

A key focus of DNDi’s work on Chagas is developing treatments that work for and are adapted to children—treatments that taste OK, come in small tablets, and so forth. To tackle this, DNDi brought together a state pharmaceutical lab in Brazil, a hospital in Argentina, an R&D center in Argentina, the University of Liverpool in the UK, biotech companies and screening companies in Australia, Barcelona, and the US into an incredible virtual network.

What is the role of the North American office?

A bit like MSF, DNDi is an international network of people working toward the same goals. In the US, our most important role is facilitating good strategic relations with policy-makers, civil society organizations concerned with global health and R&D, academia, the pharmaceutical and biotech industries, and advocating for the US government to finance research into neglected diseases and adopt policies that will enable greater needs-driven R&D. We also need financial support from private US donors–foundations, certain corporations, and individuals who believe in what we are doing.

Why does DNDi include pediatric HIV in its portfolio?

DNDi fights for new treatments for neglected patients, not just neglected diseases. If we see a glaring gap and think we are uniquely situated to help, we’ll get involved. Some 2.5 million children under the age of 15 have HIV. More than 90 percent of them are in Africa. Without treatment, one-third will die by the age of one, and half will die by the age of two. Yet only a fraction has access to antiretroviral therapy, partly because diagnosis is difficult in children, and partly because of a lack of child-friendly formulations. There are not many children with HIV in wealthy countries, which means children with HIV are not a lucrative market for the pharmaceutical industry.

Our first step is to identify key experts and potential partners in this field, and to create a target product profile to guide our strategy. It’s already clear that first-line treatments for children under the age of three are what is most needed right now.

How is MSF field work different from drug development with DNDi?

The time horizon is different, but the needs are just as urgent. There is definitely an MSF heritage in DNDi, a similar drive coupled with a realistic sense of how long it will take to bring improvements to patients. We need to make sure neglected diseases are on the political agenda, that the money is there for R&D, that the pharmaceutical industry, policy-makers, academic researchers, and governments get the message. We are talking about developing drugs for the future, but the actual needs are for today.

To learn more and find out how to support DNDi, go to DNDi.org

 

Tags: Access to Medicines, Neglected Diseases, Chagas Disease, Malaria, Paediatric Care, HIV/AIDS