Concept and Preliminary Proposal
The concept paper introducing the DNDi, a needs-driven global drug development network that will seek to correct the current market and public policy failure in R&D for neglected diseases. This paper describes the basic characteristics of the DNDi, and outlines prospective actors and financial support.
Drug research and development for developing country diseases is at a virtual standstill. Of the 1393 new drugs approved between 1975 and 1999, only 16 (or just over 1%) were specifically developed for tropical diseases and tuberculosis, diseases which account for 11.4% of the global disease burden.
Neglected diseases are seriously disabling or life-threatening diseases which mainly affect people in developing countries, and for which treatment options are inadequate or do not exist. Neglected diseases do not constitute a valuable enough “market” to stimulate adequate R&D for new medicines by traditional drug developers – the R&D-based pharmaceutical industry.
In 1999, through its Campaign for Access to Essential Medicines, Médecins Sans Frontières (MSF) convened a team of international experts – the Drugs for Neglected Diseases Working Group (DND-WG) – to study the crisis in drug research and development (R&D) for neglected diseases. This working group has focused on identifying the social, economic, technical and political factors that contribute to the present crisis, and has worked towards developing innovative strategies to ensure the development of new and affordable medicines for neglected diseases.
The DNDi: Beyond Market Mechanisms
Recent international efforts to revive pharmaceutical R&D for neglected diseases have focused mainly on malaria, tuberculosis and HIV/AIDS. These have relied heavily on market-based incentive mechanisms, including public-private partnerships. The DND-WG’s analysis clearly shows that this strategy will have limited impact for what we describe as the “most neglected diseases”. These are diseases such as sleeping sickness, Chagas disease or leishmaniasis, for which a global drug market is virtually non-existent. Ensuring the development and availability of treatment for these diseases will require a paradigm shift from market-driven to needs-driven drug development, with public responsibility and leadership in both developing and developed countries.
One such potential strategy is the creation of a needs-driven global drug development network – the Drugs for Neglected Diseases Initiative (DNDi) – that will seek to correct the current market and public policy failure in R&D for neglected diseases. The DND-WG and potential partners in developing and developed countries are currently exploring this concept and its viability, and defining enabling conditions for such an initiative. The basic elements of the DNDi concept are outlined below.
The DNDi will be an independent, needs-driven, not-for-profit entity with a vision to seek equitable access to new drugs, and an explicit mission to lead research and development for new drugs for the most neglected diseases. To fulfil its aims, the DNDi will establish working partnerships between researchers in developing and developed countries (both North-South and South-South networks), and seek sustainable ways to transfer technology and build capacity for drug research and development in developing countries.
Characteristics of the DNDi
Not-for-profit and needs-driven
The DNDi will differ from market-driven drug development in two critical respects: it will be guided by a clear focus on the most neglected diseases, going where others cannot or choose not to go; and it will be driven by need rather than return on investment. Because the DNDi will not seek profit, drugs will be available at cost.
The DNDi’s primary focus is to develop drugs for the most neglected diseases of the most neglected patients, but it is also open to developing diagnostic methods and / or vaccines as needs and means demand. In addition to identifying and developing new chemical entities, the DNDi will seek to develop and register novel combinations and indications of existing drugs, and reformulate existing products to improve use. In particular, DNDi will adapt treatments to meet patient needs, and the actual requirements of delivery infrastructure and capacity in developing countries. A complementary focus of DNDi will be to invest in sustainable capacity and leadership in developing countries at all stages of R&D.
Although the DNDi will build relationships with government, industry, and public sector research entities, its decision-making will be operationally, financially, and politically independent of each. Its choice of research portfolios, R&D partners, compounds, and ‘go/no go’ decisions will be made independently, based on sound scientific and merit criteria.
Developing countries: key players
Developing countries will be key players at all levels of the DNDi, particularly those countries directly affected by the diseases addressed through the DNDi. Their public research and technology institutions will contribute actively to R&D efforts and they may conduct clinical trials and manufacture drugs.
The DNDi will proactively build R&D networks around specific drug development projects, and co-ordinate project management to take drug candidates through the development pipeline. Rather than seeking collaborators and research innovations through a “call for projects”, the DNDi will identify research groups worldwide that produce quality relevant research, and invite them to collaborate on new research initiatives.
Public leadership in and responsibility for the DNDi will be vital. Political support from developing and developed country governments must translate into sustainable financing and pragmatic operational assistance. In concrete terms, this will mean that public institutions will need to offer direct financial support, secondment of experienced personnel and in-kind contributions.
Relations with pharmaceutical companies
The DNDi may wish to enter into collaborations with pharmaceutical and biotech firms in both developing and developed countries, particularly when specific expertise or tools are not available in the public sector. Private sector collaborations will be on a contractual basis, even when pro bono collaboration is possible. Needs may include, for example, access to compound libraries to test a potential drug target, high capacity screening, medicinal chemistry, new technologies and expertise in scaling-up, or industrial production development.
Regulatory and registration needs will be explored primarily with registration authorities in the developing countries concerned by the diseases. The standard of studies and documentation will match relevant authoritative scientific and drug registration requirements.
Intellectual property rights
The DNDi seeks to develop drugs for neglected diseases as global public goods. Intellectual property rights will be dealt with as needed on a project-by-project basis, with the sole objective of securing equitable access to drugs in developing countries.
Pharmaco-economic analysis for DNDs
The choice between competing projects will not be based on return on investment, but other economic factors will need to be considered. On the drug R&D side, the DNDi will consider different options for development in order to achieve minimum cost of R&D. On the demand side, the DNDi will conduct needs assessment and prospective sales revenue to try to secure a market for its products.
For new medicines produced by the DNDi to reach patients in need, all Founder Members, Associate Members and countries will need to join efforts to proactively address production, distribution, import conditions and pricing.
The DNDi will be supported by both public and private funding. It will manage drug development through targeted co-ordination, collaboration, and information sharing among a wide range of partners in developing and developed countries. These will include biotechnology and pharmaceutical enterprises, academic and public research centres, and R&D networks associated with newly emerging public-private partnerships.
The DNDi has already embarked upon four pilot projects to develop specific treatments for chloroquine-resistant malaria, leishmaniasis, and human African trypanosomiasis. Building on this experience, the DNDi will develop other drug development portfolios for these and other neglected diseases.
Organization and Management of DNDi
The DNDi will be led by a small team working directly with drug R&D networks. Management of operations will be decentralised, particularly to developing countries. DNDi staff will be highly skilled individuals committed to developing medicines in ways that can also build sustainable drug R&D capacity and leadership in developing countries.
An Executive Director and management team with clearly delineated responsibilities and decision-making authority will lead the day-to-day workings of the DNDi. These duties will include target disease selection, management of drug development portfolios, and advocacy. The Executive Board will provide overall guidance to ensure adherence to the mission and will work with the Executive Director as public advocates. Scientific Advisory Committees will inform executive decisions on individual projects.
The DNDi will use existing external physical resources wherever possible, for instance making use of donated laboratory and office facilities, equipment, research services, and personnel seconded from public and private organizations. In-house basic research capacity will be supported only in instances where other research avenues are not feasible.
The DNDi will be composed of Founder Members, Executive Board Members, Associate Members, and financial supporters. Founder Members will determine the mission of the initiative and contribute to the project’s launch and implementation (human and financial resources, science and technology, in kind). They will each select an Executive Board Member to govern the initiative. Executive Board Members will serve for a limited period of time in their capacity as individuals and experts, and will not represent the direct interests of Founder Members. The Executive Board will invite Associate Members to join the DNDi. Associate Members will participate in the projects’ implementation through human and financial resources, science and technology, and in kind contributions. Funds will be sought primarily from the public sector and complemented by support from private foundations and fund-raising campaigns. Financial supporters will be distinct and independent of the governance and decision-making processes of the DNDi.
DND Working Group
The DNDi will use the DND Working Group’s expertise as needed, benefit from the DND Working Groups’ advocacy activities and contribute to this by bringing specific questions to the table. The DND Working Group will continue to conduct analyses and advocate for the DNDi and other initiatives stimulating R&D for neglected diseases.
Co-ordination with TDR
Collaboration in agenda-setting and technical partnership with the UNDP/World Bank/WHO co-sponsored Special Programme for Research and Training in Tropical Diseases (TDR) will be necessary to ensure complementary in both actions and financing. It is also vital that TDR continue to use its partners (including the DNDi) to foster capacity building in, and technology transfer to, the developing world. This will be particularly relevant with regard to new science and technologies.
The DNDi will require intense public sector backing. In preliminary discussions, government representatives from both developing and developed country governments have expressed strong support for the DNDi’s aims, and have responded positively to their envisaged collaborative role in the DNDi.
To support a pipeline of projects and allow early, promising leads to mature, stable, predictable, multi-year funding will be needed. At maturity, it is anticipated that private sources will provide approximately 30% of DNDi’s annual budget, with the remainder originating in the public sector. A business plan for the DNDi, as well as investigations on legal and fiscal issues, are currently underway as part of the DNDi feasibility study.
We must act now to create a long-term solution to the crisis in research for drugs for neglected diseases. The Drugs for Neglected Diseases Initiative will ensure development of drugs by managing R&D networks which prioritise need over profitability. The DNDi’s mission, structure and actions will be governed by one imperative: to meet the R&D needs for the most neglected diseases of the most neglected patients.