Drugs for Neglected Diseases Initiative

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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,[1] malaria, paediatric HIV,[2] and specific helminth infections.

Acting in the public interest and to respond to patients’ needs, DNDi bridges the existing R&D gaps in essential drugs for these diseases by leading drug R&D projects in collaboration with the international research community, the public sector, the pharmaceutical industry, and other relevant partners.[3] The initiative’s primary objective is to deliver 11 to 13 new treatments by 2018 for these diseases and to establish a strong R&D portfolio. In doing so, DNDi is also working to use and strengthen existing capacities in disease-endemic countries, and advocate for the need to develop new treatments for the most neglected diseases. To date, DNDi has built the largest ever R&D portfolio for the kinetoplastid diseases (leishmaniasis, HAT, and Chagas) and has delivered 6 new treatments: 2 for malaria, 1 for HAT, 2 for visceral leishmaniasis, and 1 for Chagas disease.

Led by its Executive Director Bernard Pécoul,[4] DNDi’s headquarters are in Geneva, Switzerland, with offices in Kenya, India, Brazil, Malaysia, Japan, the Democratic Republic of Congo, and an affiliate in the USA.


Despite major advances in drug development in recent decades, essential medicines to treat many diseases that affect the world’s poor are either too expensive, no longer produced, highly toxic, or ineffective. Well aware of these issues from its field experience in poor and remote areas, the humanitarian organization Médecins Sans Frontières committed its 1999 Nobel Peace Prize funds to develop an alternative model for the research and development (R&D) of new drugs for neglected diseases.

As a result, in 2003, seven organizations from around the world joined forces to establish DNDi: • five public sector institutions – 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 • one humanitarian organization, Médecins sans Frontières (MSF) • one international research organization, the Special Programme for Research and Training in Tropical Diseases (TDR), which acts as a permanent observer to the initiative.

DNDi won 2012 BBVA Foundation Frontiers of Knowledge Award in the Development Cooperation category for developing and delivering new, effective and affordable treatments for poverty related diseases including Chagas disease, sleeping sickness, malaria and leishmaniasis affecting the world’s most vulnerable populations.

Current projects[edit]

Working in partnership with private industry, public institutions, academia and NGOs, DNDi has built the largest ever R&D portfolio for the kinetoplastid diseases and has currently underway six projects in Implementation stage, seven in the clinical,[5][6][7] and nine in the pre-clinical.

Adverse Effects and Patient Compliance[edit]

Some anti-infective agents are known to have some side effects, which limits their use for mono-therapies only. This poses a limitation for their use in combination therapy, for overcoming drug resistance. Also, some of the side effects may lead to a low level of compliance by the patient, i.e. not completing the full course of treatment. This creates conditions within the patient that enable drug resistance to arise or even to become prevalent. In view of such situations it is often recommended that novel anti-infective agents need to be discovered and developed.

Drug Resistance[edit]

Drug resistance occurs for several reasons, often as a natural consequence of gene mutations and selection, as a consequence of drug-efflux mechanisms, or due to drug modifying enzymes. Under conditions of medical treatment, mutants that are resistant to the drug may escape the drug's action, survive and multiply further. This is one of the reasons why combination therapies are often essential for treating most infectious diseases. In view of the contagious nature of infections, drug resistance is considered to be a serious public health issue.

Combination Therapies[edit]

Investigational New Drugs[edit]

Investigational new drugs (IND) are clinical candidates that are safe and efficacious in the animal models of infection. Usually, these are new chemical entities (NCE) with a novel mechanism of action. Investigational new drugs have to be approved by the national or international medical regulatory authorities, for clinical testing and development in humans. IND's are usually discovered and developed to overcome the limitations of drugs that are or have been in clinical use.

Clinical Research[edit]

The Pathogen Box[edit]



Genomes of protist pathogens[edit]

Structural Genomics Consortium[edit]

in silico Drug Discovery[edit]

Research & Development Centre[edit]

Research and Development Centres (R&D) for infectious diseases usually are staffed with scientists and physicians in the fields of biology, chemistry, physics, mathematics, pharmacology, veterinary science and medicine. Depending on the number of projects, it is a common practice for these research and development Centres to be staffed with about 150 scientists and physicians, with an organizational framework that is appropriate for pharmaceutical research and development. In very specialized areas, the services of contract research organizations are exploited. Thereby new assets and intellectual property are developed and patented, and are published in leading scientific and medical journals. Keynote lectures are presented at scientific and medical conferences in the field of infectious diseases, worldwide.

Animal Health and Veterinary Medicine[edit]

In view of the similarities between the parasite species that affect humans and animals the high scope for synergy in discovering new medicines for veterinary infections is of special significance and importance. This is of special interest for live-stock such as cattle, poultry, and companion animals.




To date, DNDi has made available 6 new treatments for neglected diseases:

ASAQ for malaria, 2007

Launched in 2007, this antimalarial product is the fixed-dose combination of artesunate/amodiaquine (ASAQ). It is the result of an innovative partnership between DNDi and Sanofi. Produced in Marocco, this product is cheap (available at only 0.5$ for children, 1$ for adults), administered in a simple regimen (1 or 2 tablets once a day for 3 days) and meets the latest WHO guidelines for the treatment of malaria (recommendation of treating malaria with Artesunate-based Combination Therapies – ACTs). End 2011, ASAQ was registered in 30 sub-Saharan countries, in India, and in Colombia, and more than 120 million treatments had been distributed.[8][9]

ASMQ for malaria, 2008

The second antimalarian treatment developed by DNDi is a fixed-dose combination of artesunate and mefloquine launched in 2008. Developed by a collaboration between DNDi, Brazil and South-East Asia within the FACT Project Consortium, this product consists of a 2-in-1 combination ensuring that both drugs are taken together in correct proportions. It has a simple and adapted regimen, a 3 years shelf life and a very high compliance rate. ASMQ is produced in Brazil by Farmanguinhos/Fiocruz and was registered there in 2008. Thanks to a South-South technology transfer, it is now also produced by Cipla and registered in India (2011).[10]

NECT for sleeping sickness, 2009

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.[11] Result of a six-year partnership between NGOs, governments, pharmaceutical companies, and the WHO, it was launched in 2009 and included in the WHO Essential Medicines List. It is cheaper and requests shorter hospitalization than previous treatment. It is much safer than the previously widely used arsenic-based Melarsoproll that kills 5% of the patients. In 2011, it was available in 12 African countries that account for 99% of reported HAT cases.[12][13]

SSG&PM for visceral leishmaniasis, 2010

SSG&PM, a sodium stibogluconate plus paramomycin combination therapy, is a shorter-course, cost-efficient treatment option against Visceral Leishmaniasis 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 World Health Organization (WHO).[14]

Visceral leishmaniasis treatments in Asia, 2011

In 2010, a study investigating the three possible 2-drug combinations of amphotericin B (AmBisome), miltefosine and paromomycin was completed in India. All three combination treatments were shown 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.[15]

Paediatric benznidazole for Chagas disease, 2011

It is the only paediatric dosage treatment for Chagas disease, launched in 2011 through a collaboration between DNDi and LAFEPE (Laboratório Farmacêutico do Estado de Pernambuco). It is designed for infants and young children under 2 years of age (20 kg body weight) infected congenitally. Thanks to its age‐adapted, easy‐to‐use, affordable, and non‐patented tablet, the new treatment contributes to improved dosing accuracy, safety, and adherence to treatment. Paediatric benznidazole was granted registration by Brazil’s National Health Surveillance Agency (ANVISA), with further endemic countries targeted for obtaining registration.

Disease-specific regional platforms[edit]

DNDi works closely with partners in disease-endemic countries to strengthen existing clinical research capacity as well as to build new capacity where necessary. DNDi helped in setting up and works with 3 regional disease-specific platforms in Africa and Latin America:

• The Leishmaniasis East Africa Platform (LEAP) on leishmaniasis

• The HAT Platform on sleeping sickness, or human African trypanosomiasis

• The Chagas Clinical Research Platform (CCRP) on Chagas disease

Their mission is to define patients needs, taking into consideration the local conditions, bring together key regional actors in the field of health, reinforce clinical capacities in endemic regions, address infrastructural requirements where necessary and provide on-site trainings. These platforms contribute to increase the chances of registration, uptake, and sustainable access of new treatments.

See also[edit]


  1. ^ Nature Outlook Chagas Disease supplement. Nature Supplement, 2010 June, Vol. 465, No. 7301 suppl. ppS3-S22
  2. ^ Pediatric HIV - A Neglected Disease ? by Lallemant M, Chang S, Cohen R, and Pécoul R. The New English Journal of Medicine. 2011 August. 365:581-583.
  3. ^ Future Medicinal Chemistry, "DNDi model of drug development for neglected diseases: current status andfuture challenges" - September 2011
  4. ^ The Lancet, "Bernard Pécoul: championing the cause of neglected diseases" - August 2010
  5. ^ SCYX-7158, an Orally-Active Benzoxaborole for the Treatment of Stage 2 Human African Trypanosomiasis by Jacobs R.T, Nare B, Wring S.A, Orr M.D, Chen D, Sligar J.M, Jenks M.X, Noe R.A, Bowling T.S, Mercer L.T, Rewerts C, Gaukel E, Owens J, Parham R, Randolph R, Beaudet B, Bacchi C.J, Yarlett N, Plattner J.J, Freund Y, Ding C, Akama T, Zhang Y-K, Brun R, Kaiser M, Scandale I, Don R. PLoS NTD. 2011 June. e1151. doi:10.1371/journal.pntd.0001151
  6. ^ Synthesis of 2H- and 14C-labeled fexinidazole and its primary metabolites labeled with 2H by E. Fontana, Alberto Pignatti, Serena Venegoni, and Michael A. Bray. The Journal of labelled compounds and radiopharmaceuticals. August 30, 2011. doi:10.1002/jlcr.1914
  7. ^ Novel 3-Nitro-1H-1,2,4-triazole-based Aliphatic and Aromatic Amines as anti-Chagasic Agents by Maria V. Papadopoulou , Bernadette Bourdin , William D Bloomer , Caroline McKenzie , Shane R. Wilkinson , Chaiya Prasittichai , Reto Brun , Marcel Kaiser , and Els Torreele. Journal of Medicinal Chemistry, Online, October 24, 2011
  8. ^ Innovative public-private partnerships to maximize the delivery of anti-malarial medicines: lessons learned from the ASAQ Winthrop experience by Bompart F, Kiechel J-R, Sebbag R, Pecoul B. Malaria Journal. May 2011, 10:143 doi:10.1186/1475-2875-10-143
  9. ^ The initial pharmaceutical development of an artesunate/amodiaquine oral formulation for the treatment of malaria: a public-private partnership by Lacaze C, Kauss T, Kiechel J-R, Caminiti A, Fawaz F, Terrassin L, Cuart S, Grislain L, Navaratnam V, Ghezzoul B, Gaudin K, White N.J, Olliaro P, Millet P. Malaria Journal. May 2011, 10:142 doi:10.1186/1475-2875-10-142
  10. ^ Krudsood, S.; Looareesuwan, S.; Wilairatama, P.; Leowattana, W.; Tangpukdee, N.; Chalermrut, K.; Ramanathan, S.; Navaratnam, V. et al. (2011). "Effect of artesunate and mefloquine in combination on the Fridericia corrected QT intervals in Plasmodium falciparum infected adults from Thailand". Tropical Medicine & International Health 16 (4): 458. doi:10.1111/j.1365-3156.2010.02714.x. 
  11. ^ The Guardian, "New treatments raise hope of cutting sleeping sickness deaths" - May 2010
  12. ^ NECT Is Next: Implementing the New Drug Combination Therapy for Trypanosoma brucei gambiense Sleeping Sickness by Yun O, Priotto G, Tong J, Flevaud L, Chappuis F. PLoS NTD, 2010 May, 4(5):e720
  13. ^ Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial by Priotto G, Kasparian S, Mutombo W, Ngouama D, Ghorashian S, Arnold U, Ghabri S, Baudin E, Buard V, Kazadi-Kyanza S, Ilunga M, Mutangala W, Pohlig G, Schmid C, Karunakara U, Torreele E, Kande V. In Lancet. 2009; 374:56-64.
  14. ^ Visceral leishmaniasis treatment: What do we have, what do we need and how to deliver it? By Lucio H. Freitas-Junior, Eric Chatelain, Helena Andrade Kim, Jair L. Siqueira-Neto. International Journal for Parasitology: Drugs and Drug Resistance, Volume 2, December 2012
  15. ^ Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: an open-label, non-inferiority, randomised controlled trial by Sundar S, Sinha P.K, Rai M, Verma D.K, Nawin K, Alam S, Chakravarty J, Vaillant M, Verma N, Pandey K, Kumari P, Lal C.S, Arora R, Sharma B, Ellis S, Strub-Wourgaft N, Balasegaram M, Olliaro P, Das P, Modabber F. Lancet, 2011 January, doi:10.1016/S0140-6736(10)62050-8.

External links and publications[edit]