The Drugs for Neglected Diseases initiative (DNDi) is a collaborative, patients' needs-driven, non-profit drug research and development (R&D) organization that is developing new treatments for neglected diseases, notably leishmaniasis, sleeping sickness (human African trypanosomiasis, HAT), Chagas disease,Nature Outlook Chagas Disease supplement. Nature Supplement, 2010 June, Vol. 465, No. 7301 suppl. ppS3-S22 malaria, filarial diseases, mycetoma, paediatric HIV, cryptococcal meningitis, hepatitis C, and dengue. DNDi's malaria activities were transferred to Medicines for Malaria Venture (MMV) in 2015.
Led by Executive Director Luis Pizarro, DNDi has offices in Switzerland (Geneva), Brazil, the Democratic Republic of Congo, India, Japan, Kenya, Malaysia, and an affiliate in the United States.
Origins
Despite the major progress achieved in medicine during the past 50 years, many tropical diseases affecting the poorest are still neglected. More than a billion peopleWorld Health Organization, 2019. – more than a seventh of the world's population – are infected with one of the 20 diseases listed by the World Health Organization (WHO) as neglected tropical diseases.Third WHO report on neglected tropical diseases, Investing to overcome the global impact of neglected tropical diseases, 2015. Although neglected tropical diseases can be fatal, there is a lack of modern, safe and effective medications to treat these illnesses.
Evidence of the lack of new drugs for diseases that cause high mortality and morbidity among people living in poor areas has been published in the scientific literature. One publication reported that only 1.1% of new drugs were approved specifically for neglected diseases over a period of 25 years (1975 to 1999) despite the fact that these diseases represented 11.4% of the global burden."Drug Development For Neglected Diseases: A Deficient Market and a Public-Health Policy Failure" By Patrice Trouiller, Piero Olliaro, Els Torreele, James Orbinski, Richard Laing, and Nathan Ford. The Lancet. June 22, 2002. Another indicated that this trend remained the same between 2000 and 2011 with only 1.2% of the new chemical entities brought to market indicated for neglected diseases.The drug and vaccine landscape for neglected diseases (2000—11): a systematic assessment By Belen Pedrique B, Strub-Wourgaft N, Some C, Olliaro P, Trouiller P, Ford N, Pécoul B, Bradol JH. The Lancet Global Health, October 2013.
DNDi was created in 2003 to develop new treatments for neglected diseases. The organization was set up by key research and health institutions, notably from the public sector in neglected-disease-endemic countries – the Oswaldo Cruz Foundation from Brazil, the Indian Council of Medical Research, the Kenya Medical Research Institute, the Ministry of Health of Malaysia and France's Pasteur Institute, with seed funding from Médecins Sans Frontières' (MSF) 1999 Nobel Peace Prize. The WHO Special Programme for Research and Training in Tropical Diseases (TDR) acts as a permanent observer to the initiative.
DNDi's founder Bernard Pécoul led the organization from 2003 until 2022.
From 2022 until now, the organization has a new director, a Chilean doctor called Luis Pizarro.
Non-profit drug development model
As people with neglected diseases do not represent a lucrative market for pharmaceutical companies, incentives to invest in research and development are lacking for these diseases.Fatal Imbalance: The Crisis in Research and Development for Drugs for Neglected Diseases". MSF Campaign for Access to Essential Medicines and Drugs for Neglected Diseases Working Group. Geneva, 2001.«Kinetoplastida: New Therapeutic Strategies" By Croft SL. Parasite 2008; 15:522-27
Alternatives to profit-driven drug development emerged in the early 2000s to meet the needs of these neglected patients. Product development partnerships (PDPs), also called public-private partnerships (PPPs) aim to implement and accelerate research and development (R&D) into health tools (diagnostics, vaccines, drugs) for diseases that are neglected, by enabling new collaborations between private industry, academia, and the public sector.« Drug Development for Neglected Tropical Diseases : DNDi and the Product Development Partnership (PDP) Model », Julia Tuttle, A thesis submitted to the Department of Global Health for honors, Duke University, 2016. Examples of PDPs include the International AIDS Vaccine Initiative, MMV, the Global Alliance for TB Drug Development (TB Alliance), and DNDi.
PDPs act as 'conductors of a virtual orchestra',« Ten years of experience & lessons learned by DNDi », DNDi, 2014. leveraging partners' specific assets, capacities, and expertise to implement projects at all stages of the R&D process, integrating capabilities from academia; public-sector research institutions, particularly in neglected disease-endemic countries; pharmaceutical and biotechnology companies; non-governmental organizations including other PDPs; and governments worldwide.
To overcome the lack of commercial research into drug development, PDPs can apply "delinkage" principles that aim to separate the cost of research and development from the price of products. This allows the incentive for investing in a particular disease to be independent of the price at which any developed products will be sold.« Drug Development for Neglected Tropical Diseases : DNDi and the Product Development Partnership (PDP) Model », Julia Tuttle, A thesis submitted to the Department of Global Health for honours, Duke University, 2016.
Key achievements DNDi has built a large drug pipeline for neglected diseases with both improvements on existing drugs and entirely new chemical entities. To date, their 13 key achievements are
Treatments delivered to date:
ASAQ, fixed-dose combination for malaria, 2007
Launched in 2007, this antimalarial product is a fixed-dose combination of artesunate/amodiaquine (ASAQ). The result of a partnership between DNDi and French pharmaceutical company Sanofi, ASAQ, which is produced in Morocco, is affordable (available for only $0.05 for children, $1 for adults), is administered in a simple regimen (1 or 2 tablets per day for three days), meets the latest WHO guidelines for malaria treatment in Africa and was granted "pre-qualified" status in 2008. Although developed without a patent, ASAQ is included in the WHO Model List of Essential Medicines and Essential Medicines List for Children, is registered in 32 African countries, India, Ecuador, and in Colombia, and more than 437 million treatments have been distributed.
A technology transfer agreement has been signed with industrial partner Zenufa in Tanzania in order to provide an additional source of ASAQ. ASAQ was handed over to the MMV Access and Product Management Team in May 2015.
ASMQ, fixed-dose combination for malaria, 2008
The second antimalarial treatment developed by DNDi is a fixed-dose combination of artesunate and mefloquine launched in 2008. It was developed by an international collaboration within the FACT Project Consortium. It has a simple and adapted regimen, a three-year shelf-ife and a very high compliance rate. ASMQ is produced in Brazil by /Fiocruz and thanks to a South–South technology transfer, it is now also produced by Cipla. The latter was granted "pre-qualified" status by the WHO in 2012 and included on the WHO Model List of Essential Medicines and Essential Medicines List for Children in 2013. By 2015 it was registered in Brazil, India, Malaysia, Myanmar, Tanzania, Vietnam, Niger, Burkina Faso, Thailand and Cambodia. By the end of 2015 more than one million treatments had been distributed. ASMQ was handed over to the MMV Access and Product Management Team in May 2015.
NECT, improved treatment for sleeping sickness, 2009
Nifurtimox-eflornithine combination treatment (NECT), a combination therapy of nifurtimox and eflornithine, is the first new, improved treatment option in 25 years for stage 2 (advanced stage) human African trypanosomiasis (HAT) also known as sleeping sickness. It is the result of a six-year partnership between NGOs, governments, pharmaceutical companies, and the WHO. It was launched in 2009 and included on the WHO Model List of Essential Medicines and WHO Essential Medicines List for Children in 2009 and 2013 respectively. It requires shorter hospitalization than previous treatment, and is much safer than previously widely used arsenic-based melarsoprol that killed about 5% of patients. NECT is now used to treat 100% of the patients infected with HAT stage 2 in all 13 endemic countries.
SSG&PM, combination treatment for visceral leishmaniasis, 2010
SSG&PM, a sodium stibogluconate plus paromomycin combination therapy, is a shorter-course, cost-efficient treatment option against visceral leishmaniasis (VL) in East Africa available since 2010. It is the result of a six-year partnership between DNDi, the Leishmaniasis East Africa Platform (LEAP), the National Control Programmes of Kenya, Sudan, Ethiopia, and Uganda, Médecins Sans Frontières (MSF) and the WHO. It was recommended by the WHO Expert Committee on the Control of Leishmaniasis in 2010 as the first-line treatment in East Africa, and more than 10,000 patients have been treated. Sudan, Ethiopia, South Sudan and Somalia have released revised guidelines recommending SSG&PM as the first-line treatment for VL.
Combination treatments for visceral leishmaniasis in Asia, 2011
Single dose amphotericin B and paromomycin/miltefosine/amphotericin B combinations were recommended by the WHO Expert Committee on the Control of Leishmaniasis (2010). These treatments are less toxic than previous mainstay treatments, useful in areas of antimonial resistance, are shorter course and their cost is comparable with previous treatments. In 2010, a study investigating the three possible 2-drug combinations of amphotericin B, miltefosine and paromomycin was completed in India. All three combination treatments were shown to be highly efficacious (> 97.5% cure rate). A WHO Expert committee recommended these treatments to be used preferentially to current established monotherapy treatments for VL in South Asia. DNDi is working with TDR and WHO to facilitate their introduction and support VL elimination strategies. DNDi conducted more studies, including a pilot project in the Bihar State of India (2012–2015) that demonstrated the safety and effectiveness of combination therapies based on amphotericin B, miltefosine, and paromomycin at the primary healthcare level, and single dose amphotericin B at the hospital level. Based on the study results, the Indian National Roadmap for Kala-Azar Elimination in August 2014 recommended use of single dose amphotericin B as a first option treatment for the treatment of VL patients, with paromomycin and miltefosine as a second option at all levels; a policy also reflected in Bangladesh and Nepal. This removal of miltefosine monotherapy is an important policy change. This project has been a collaboration with a consortium of partners.
Paediatric benznidazole for Chagas disease, 2011