REMAINING RESPONSIVE TO EVOLVING RESEARCH AND PATIENT NEEDS
Message from Dr Bernard Pécoul, Executive Director and Professor Marcel Tanner, Chair of the Board of Directors
DNDi is rooted in an ideal: to mobilize scientific innovation to create new medicines for the world’s most neglected diseases and malaria. Our aim was to provide the structure to take the most promising projects ignored by commercial drug development through the pipeline, by capitalizing on existing capacity and expertise, particularly in affected countries.
Since its inception in 2003, DNDi has defined itself as an experiment in ‘innovation for access,’ a laboratory for alternative mechanisms that deliver affordable products answering to an unaddressed medical need. Our scale is by definition small: our purpose is not, and never has been, to act as the solution to systemic failures of biomedical R&D.
Our six achievements to date, attained in collaboration with our partners, bear witness to the pertinence of that initial ideal and the success of the model – with two new antimalarial fixed-dose combinations, the world’s first child-friendly medication for Chagas disease, and changes to national or international guide lines, thanks to successful clinical trials for sleeping sickness and for visceral leishmaniasis treatments in Africa and Asia.
More than a decade later, it is our pleasure to take stock once again.
An unchanged vision, an expanded mission
In 2014 and 2015, we embarked on an extensive consultation exercise with our founding partners and key stakeholders, as well as with leading global health actors, to ensure the organization remains attuned to current and emerging patients’ needs and the evolving R&D landscape.
The outcome of the consultation, enshrined in the new Business Plan for 2015 to 2023, maintains our focus on the most neglected diseases by adopting a dual strategy: on the one hand, pursuing incremental innovation to bring therapeutic benefits to patients by repurposing, reformulating, or combining existing drugs; and on the other, seeking to discover and develop entirely new chemical entities, with the aim of bringing radically improved oral treatments without which sustainable control or elimination of these diseases can never become a reality.
Discovering and developing treatments to respond to neglected tropical diseases like sleeping sickness, visceral and cutaneous leishmaniasis, Chagas disease, and filaria remain at the core of our work. Adding to this focus on the most neglected of the neglected, a new research and development project will focus on new treatments for mycetoma, a devastating infection – recently introduced on the official WHO list of neglected tropical diseases – which, left untreated, eventually results in amputation.
While our core focus remains unchanged, we acknowledge that the shortcomings of the existing system of research and development extend far beyond the neglected diseases at the core of DNDi’s portfolio. From our consultations, three main findings emerged to help us draw lessons for the future of DNDi’s model and operations: first, R&D priorities do not sufficiently originate from low- and middle-income countries (LMICs);
secondly, patients’ needs are not prioritized, and many treatment needs, for example for Ebola or mycetoma, are left unaddressed; and finally, market incentives that solely rely on intellectual property and exclusivity rights do not adequately address health needs in LMICs, with certain public health needs like antimicrobial resistance left unanswered as a result.
We also noted changes in global health epidemiology, with for example the emergence of new infectious disease risks and LMICs facing a double burden of both communicable and non-communicable diseases. The political context of global health is also evolving, with the lack of equitable access to new health tools increasingly seen as a problem, including in high-income countries as, for example, in hepatitis C. The challenge is therefore better understood as one of “neglected diseases, neglected patients and populations in neglected health and social systems”– that is, of ensuring that the global R&D system meets the needs of all, especially of the poorest and most vulnerable populations in the most neglected settings.
A dynamic and pragmatic approach to ensure DNDi can respond to changing needs
Given the complexities of drug discovery and development, the timelines of a research and development organization are lengthy. By essence, our commitments and objectives are long term. The challenge lies in continuing to meet these, while also ensuring DNDi remains relevant and responsive to the evolving needs of patients.
Within this rapidly changing landscape, DNDi’s new Business Plan for 2015 to 2023 aims to give the organization the flexibility to address urgent unmet patients’ needs, by introducing the concept of a dynamic portfolio as a tool to guide the evolution of DNDi’s activities. This will involve identifying and selecting new opportunities through a detailed decision-making and evaluation framework, as well as for phasing out projects when they reach completion and/or are not part of our core activities, as was recently the case for our malaria portfolio that was transferred to the Medicines for Malaria Venture.
Ultimately, decisions to enter into new projects will always be based on patients’ needs, existing R&D opportunities, an absence of other actors in the field, and ability to engage operational partners.
This is what led DNDi to include paediatric HIV into its portfolio in 2011. Even though there is a strong R&D effort to develop better HIV/ AIDS treatments for adults, very little research is done for HIV-positive children. Current treatment options are insufficient, as little investment has been made to ensure the safety and efficacy of antiretrovirals in treating children. They are neglected patients.
We now tackle hepatitis C: Despite an abundant pipeline of potential new drugs, developing country research needs are largely unaddressed, and existing products are unaffordable. The therapeutic advances brought about by direct-acting antivirals are not reaching patients. In an exciting new project launched in April 2016, DNDi aims to foster a public health approach to the disease, by facilitating the development of an affordable pan-genotypic treatment.
DNDi will also change how it does things. Not every disease area will require the same amount of effort and investment. A range of different operating models can be used, from integration into DNDi’s R&D portfolio, to various levels of more time-limited support such as knowledge sharing, advocacy, building new resource platforms, or serving as an incubator for an idea that may ultimately be externalized. By allowing for more flexible and diversified operational models, DNDi can tailor the breadth and depth of its engagement to a specific global health R&D need as it arises without jeopardizing our focus or draining resources. Resistance to antibiotic treatments, for example, emerged as a key unmet medical need in our landscape analysis, and was considered best addressed through an incubator model, with a dedicated team.
The roadmap towards 2023
In our 13 years of existence, DNDi has developed, implemented, or delivered six new treatments, for malaria, sleeping sickness, Chagas, and leishmaniasis, and developed a pipeline of over 30 projects. By our 20th anniversary in 2023, our ambition is to have delivered 16 to 18 new treatments, including two to three new chemical entities.
Reaching this ambitious objective relies on an estimated budget of EUR 650 million covering the 20-year period since the creation of DNDi until 2023, of which close to EUR 400 million has already been secured to date.
We will stay focused on the key elements that have been essential to our success: our partnerships with private sector actors, key for us to access the necessary expertise and data to bring a treatment through to the hands of patients; the support of public actors, which has been the lifeline of our endeavours; and the participation of research communities and civil society in endemic countries to ensure patients’ needs remain at the forefront of our efforts. For this particular reason, this business plan will be translated into a regional strategic plan, with the expansion and development of DNDi’s regional offices, particularly those in neglected disease-endemic regions. These close associations, for some now more than a decade long, will remain a fundamental part of the set-up of DNDi and assure the process of mutual learning for change for the benefit of the most neglected populations in the most neglected health and social systems.
Dr Bernard Pécoul Professor Marcel Tanner
Executive Director Chairman