Stimulating research in the most neglected diseases

There is a "chronic lack of effective, affordable, easy-to-use medications for neglected diseases", asserted Els Torreele (Free University of Brussels, Belgium) last week. Torreele's audience, however, were already aware of this stark fact, since they were attending the "crisis of neglected diseases" conference on March 14 in New York, USA, organised by Médecins Sans Frontières (MSF).

This non-governmental organisation (NGO) is currently running a campaign on access to essential medicines--of which the problem of neglected diseases is a fundamental part. Recent international partnership initiatives have focused on stimulating interest in the development and provision of drugs for malaria, tuberculosis, and HIV/AIDS--"neglected diseases".

However, there are also the "most neglected diseases"--such as sleeping sickness, Chagas disease, and leishmaniasis--for which there is virtually no global drug market. Drugs for Neglected Diseases (DND) is an MSF project that started in 1999 and has brought together an international group of scientists such as Torreele, co-chair for the group, health researchers, and members of the pharmaceutical and regulatory industries.

The DND project aim has been to push forward innovative strategies to tackle neglected diseases. At the conference, the DND discussed the development of a new entity--the Drugs for Neglected Diseases Initiative (DNDi), which "would systematically harness funding, new science and technology, and public-private cooperation to develop drugs for those in need".

According to Torreele, "in the past 25 years, 1393 new chemical entities came on the market. Only 1% [13 drugs] were for tropical infectious diseases". Most of those 13 were developed for veterinary or military purposes, leaving just three that were the result of genuine effort to create drugs for neglected diseases.

This pharmaceutical market failure is also a public policy failure, said Torreele. Public policy has stimulated drug development in industrialised countries, where medicines generate profit. Central to the DNDi is the notion that drugs for neglected diseases are public goods. The initiative would therefore work to secure long-term funding from the public sector.

The public sector has historically funded health research and is still largely responsible for what is arguably the most important part of drug development--identifying useful compounds. "There are new things happening", said Ariel Pablos-Mendez, associate director of the health equity programme at the Rockefeller Foundation.

In recent decades, the academic culture has praised fundamental rather than applied research, he noted. "This of course has begun to change . . . pipelines previously dry are beginning to flow, though it takes years and lots of effort to deliver and to do it equitably", said Pablos-Mendez.

Incentive mechanisms such as tax credits or advance-purchase arrangements can be used to motivate drug development. But these efforts rely on charging market prices, which companies cannot do in the developing world.

Public private partnerships (PPPs) are an another, currently popular, "enabling environment" for neglected disease research and development. But at present "most neglected diseases are also neglected by PPPs", said Giorgio Roscigno (Global Alliance for TB Drug Development).

PPPs must shift from "sticking plaster solutions", such as donating drugs, and focus on "discovery, new diagnostics, and affordable pricing", Roscigno said. The vast majority of research and development occurs in developed countries, but emerging economies such as Thailand and India have the ability to do research from early development through production.

Although infrastructure can be fragmented in these countries, Ayoade Oduola (Special Programme for Research and Training in Tropical Diseases, WHO, Geneva, Switzerland) said we should "convince, cajole, and if necessary con" drug companies into using the existing resources in the developing world.

Intellectual property rights and regulatory standards are potential sticking points in developing nations. Reframing these issues and advocating drug-specific and disease-specific solutions may be among the most valuable of the DNDi's efforts. To expect the private sector to step in and fill these research and development gaps is a "pipe dream", noted James Orbinski of MSF and co-chair of the DND project.

"We shouldn't overlook public health responsibility to advocate for treatment drugs", he said. MSF, an organisation new to drug development, gave the DNDi US$1 million for immediate-need drugs in malaria, sleeping sickness, and leishmaniasis. DNDi will partner with organisations in Brazil, India, Thailand, and Malaysia, and with WHO's Tropical Diseases Research programme. Future funding will come from governments and international and private organisations.

The breaking down of old barriers is becoming a hallmark of new initiatives to make drugs available where they are needed rather than where they are affordable. Previously "NGOs were depicted as demagogues, industry was vilified, and governments were not doing much", noted Michel de Rosen of the biotech company, ViroPharma.

"This event would have been impossible a few years ago." Stimulating drug development clearly requires public-spirited partnerships. But how to maintain the momentum and awareness in countries where the pains of such illnesses are not routinely felt is less clear.