Disease, Disorders, Medical Disciplines
The Drugs for Neglected Diseases initiative (DNDi), North America supports DNDi's global vision and mission to develop new drugs, or new formulations of existing drugs for patients suffering from the most communicable diseases. Acting in the public interest, DNDi bridges existing R&D gaps in essential drugs for these diseases by initiating and coordinating drug R&D projects in collaboration with the international research community, the public sector, the pharmaceutical industry, and other partners.
Rachel M Cohen
40 Wall Street, 24th Floor
New York, NY 10005 USA
Neglected diseases, Chagas, Trypanosomiasis, leishmaniasis, malaria, sleeping sickness, drugs, mycetoma, hepatitis C, antibiotic resistance, antimicrobial resistance
Diseases, Disorders, Medical Disciplines N.E.C. (G99)
Research Institutes and/or Public Policy Analysis (H05)
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What are the organization's current programs, how do they measure success, and who do the programs serve?
SOURCE: Self-reported by organization
Human African Trypanosomiasis (HAT)
At its inception, DNDi’s short-term strategy was to make better use of existing treatments by combining drugs already in use. In September 2009, DNDi and partners launched the first new treatment for sleeping sickness in 25 years: nifurtimox and eflornithine combination therapy (NECT). NECT is included on the WHO Essential Medicines Lists (EML) for adults (since 2009) and children (since 2013), and all countries with endemic T. b. gambiense are now using NECT as first-line treatment for stage 2 HAT.
As a medium-term strategy, DNDi initiated a compound mining effort to identify existing chemical compounds with potential against kinetoplastid diseases, resulting in the rediscovery of fexinidazole, currently undergoing evaluation in a pivotal Phase II/III study in stage 2 HAT, with two complementary studies examining efficacy and safety in adults with stage 1 and early stage 2 HAT, and in children aged 6-14 years. Sanofi is the industrial partner.
In order to build a strong pipeline for long-term drug discovery, DNDi established a HAT Lead Optimization Consortium resulting in identification of the oxaborole SCYX-7158, which successfully progressed through pre-clinical development. Phase I clinical development is due for completion in 2015. Other backup compounds were evaluated by the consortium and remain available for further development if necessary.
In addition, DNDi supports the HAT Platform that was launched in Kinshasa, Democratic Republic of the Congo (DRC) in 2005. The HAT Platform is a clinical research and access-supporting network that brings together key players in the fight against sleeping sickness in endemic countries and those involved in HAT from the international research arena.
Ideally a new treatment for adults and children would be effective against both stages of the disease and both parasite sub-species, non-toxic, at least 95% efficacy at 18 months follow-up, safe for pregnant and breastfeeding women, easy to use (short-course or once a day), oral, requiring no monitoring, affordable and adapted to tropical climates.
By 2018, DNDi aims to deliver from its HAT-specific portfolio:
- An oral, safe, effective treatment to be used for both stage two and stage one HAT
DNDi’s short-term approach for visceral leishmaniasis was to develop new treatments by combining existing drugs and/or shortening treatment duration in order to increase tolerability, reduce burden on health systems, and offer greater affordability, whilst also preventing or delaying emergence of resistance. Another objective is the geographical extension of existing drugs in other countries and regions. In 2010, DNDi and LEAP partners delivered the SSG&PM combination therapy for East Africa, now recommended as first-line treatment for VL in the region. SSG&PM has been included in the national guidelines of Sudan, South Sudan, Ethiopia, and Kenya. PM is registered in Uganda (2011) and Kenya (2013), and is in the process of registration in Sudan and Ethiopia. In India, a Phase III trial demonstrated the efficacy of combination therapies of already registered drugs. In 2014, the government of India recommended use of single-dose AmBisome® as a first option and paromomycin/miltefosine combination as the second option for treatment instead of using miltefosine as monotherapy. DNDi has collaborated with the National Control Programmes of India and Bangladesh, MSF, the Bihar State Health Society, and the Indian Council for Medical Research to assess the effectiveness and safety of these new treatments at the primary healthcare level and facilitate their introduction. In Latin America, DNDi is participating in a study sponsored by the Brazilian Innovation Agency (FINEP) to evaluate the safety and efficacy of Glucantime®, AmBisome®, and amphotericin B as monotherapies, and of AmBisome®/Glucantime® combination to treat VL patients. The national control programme has extended the use of AmBisome® as second-line treatment based on the interim safety data from this trial.
Leishmania and HIV co-infection is a growing problem, difficult to manage clinically due to poor response to treatment with frequent relapses of disease, and is eventually fatal. DNDi is working with partners towards better treatment for HIV/VL co-infected patients in Africa using existing drugs at different dose/regimen and in combination, and is collaborating with ITM-Antwerp in a secondary prophylaxis study.
In the medium term, DNDi is assessing the combination of fexinidazole and miltefosine for the treatment of visceral leishmaniasis patients in terms of efficacy and safety. This could be the first oral-only combination therapy for visceral leishmaniasis.
DNDi’s long-term strategy for visceral leishmaniasis is to bring new oral drug candidates into clinical development through its lead optimization programme with the ultimate goal of improving the safety profile and efficacy of the existing tools with a second oral-only combination treatment.
In addition, DNDi supports the Leishmaniasis East Africa Platform (LEAP). A new visceral leishmaniasis treatment for adults and children based on a new chemical entity would ideally be efficacious against all species of Leishmania in all regions as well as against resistant strains, have at least 95% efficacy, be short course (once a day for 10 days oral; or 3 shots over 10 days), easy to use, compatible for combination therapy, safe in pregnant and breastfeeding women and for immunocompetent/immunosuppressed patients, affordable, and adapted to tropical climates.
By 2020, DNDi aims to deliver from its VL-specific portfolio:
- Potentially a safe, effective, low-cost, and short-course oral combination treatment
- A new treatment for PKDL that is shorter course and better tolerated than current options
- Treatment options for HIV/VL co-infected patients
- A new first-line treatment regimen for visceral leishmaniasis in Latin America
For cutaneous leishmaniasis, DNDi’s objective is to develop short, safe, efficacious, affordable, and field-adapted treatments, at least for lesions caused by L. tropica and L. braziliensis. As a short-term strategy, DNDi is developing a topical treatment based on amphotericin B, and aims to improve treatment strategies using currently available treatment modalities in combination.
In the medium to long term, DNDi aims to develop an oral drug and an immunemodulator for use in combination with chemotherapy. This novel approach aims to initially eliminate parasites with chemotherapy, followed by enhancement of the patient’s immune response with an immune-stimulating agent.
A new topical or oral treatment for cutaneous leishmaniasis would ideally be efficacious against all species, show at least 95% efficacy, be easy to use, short course (14-28 days), compatible for combination therapy, produce minimal scarring, be safe in pregnant and breastfeeding women, affordable and adapted to tropical climates.
By 2020, DNDi aims to deliver from its CL-specific portfolio:
- A safe, effective, and shorter-course treatment for cutaneous leishmaniasis
DNDi’s short-term goal was to make better use of existing treatments, for example through the development of a paediatric dosage form of benznidazole – a goal which was achieved in 2011. The treatment is registered in Brazil (2011), and was included on the WHO Essential Medicines List for children in 2013. An agreement signed in 2013 with the Mundo Sano Foundation will ensure a second source of the treatment previously solely manufactured by LAFEPE. Collaborative activities will continue to support country registration and adoption, and greater treatment availability to patients.
As a medium-term strategy, DNDi has been assessing known families of compounds such as the new azole antifungal drug, E1224, for activity against T. cruzi in adult chronic patients. Results from a proof-of-concept trial showed E1224 monotherapy to have some short-term effect on parasite clearance but with insufficient long-term efficacy, and the current regimen of benznidazole to be efficacious in the long term, but with side effects. Alternative benznidazole regimens, including reduced dosing and duration of treatment in monotherapy and combination treatment with E1224 are being explored. Fexinidazole, also in development for HAT and VL, is also being evaluated. Additionally, DNDi continues to search for potential biomarkers of treatment response to enhance clinical trial capabilities for evaluation of new compounds.
As part of its long-term strategy, DNDi continues to identify and engage partners from private and public sectors in order to identify, characterize, and advance the development of promising compounds as well as to pursue discovery efforts for innovative therapies.
In addition, DNDi supports clinical research capabilities and access through the Chagas Clinical Research Platform, which was launched in 2009.
Ideally, a new treatment would be for both acute and chronic phases of the disease, useful against most parasite species in all regions, with a better safety profile than existing drugs, non-inferior efficacy to benznidazole, easy-to-use (oral, once-a-day for less than 30 days, requiring no hospitalization and little or no monitoring), affordable, and adapted to tropical climates.
By 2020, DNDi aims to deliver from its Chagas-specific portfolio:
- An effective and safe new oral treatment regimen of chronic indeterminate Chagas disease, ideally also effective against the acute form of the disease
- Biomarkers to gain understanding of disease progression and ease the development of tools for evaluation of treatment response to support drug development
DNDi’s strategy is to develop a new compound with macrofilaricide activity for use as a safe and field-adapted macrofilaricidal drug for patient case management and possibly later MDA if needed.
As a medium-term strategy, DNDi is assessing emodepside, a potent antihelminthic drug used in combination with praziquantel to treat parasitic worms in cats and dogs, as a clinical candidate to treat humans.
As a long-term strategy, DNDi is assessing additional opportunities through an active screening programme of drug compounds emanating from animal health/ pharmaceutical companies and academic institutions, with the goal of selecting one or two candidates to move into clinical development.
Ideally a new treatment for adults and children will be a macrofilaricide (efficacious
against the adult form of worms), oral, short-course treatment, well tolerated, affordable, and adapted to tropical climates.
In 2010, DNDi was called on by various organizations, including Médecins Sans Frontières, WHO, and UNITAID, to apply its expertise to the development of paediatric HIV treatments. DNDi’s position, notably that paediatric HIV is a neglected disease, was published as a ‘Perspective’ in the New England Journal of Medicine in August 2011.
DNDi is pursuing two objectives to address the needs of HIV-infected children:
Develop and register two solid first-line 4-in-1 LPV/r-based fixed-dose combinations (FDCs) with two NRTIs. All components of the combination will be developed in the form of tastemasked granules, stable with no need for refrigeration, presented in a single unit with appropriate strengths to accommodate weight band dosing.
Develop and register a heat stable stand-alone ritonavir booster formulation that is well taste-masked and can be added to any PI-based paediatric ARV regimen and can be used to counteract the negative drug-drug interactions between PIs and rifampicin-containing TB treatments.
Before these formulations are made available however, as a short-term strategy, DNDi will start testing the use of PI-based treatment with existing LPV/r-based solid formulations before the availability of the 4-in-1 FDC, in order to provide better treatment for infants today and promote in-country adoption. The heat-stable pellets are already a great improvement, however the bitter taste remains and is a barrier to use in treating this chronic disease. DNDi participated in the CHAPAS-2 trial that compared LPV/r sprinkles (hereafter referred to as pellets) to the LPV/r liquid formulation. These pellets will be used in combination with NRTI dispersible tablets in implementation studies (LIVING Study).
In the longer-term, DNDi is working with its industrial partner, Cipla Ltd., on combining taste-masked LPV/r granules with two NRTIs into a single unit dose. This modular concept is flexible, so that any of the components can eventually be substituted to provide new fixed-dose combinations.
In addition, in order to address the needs of HIV/TB co-infected children, DNDi is developing a formulation of ritonavir for superboosting LPV/r at a 1:1 ratio. As a short-term strategy, DNDi is conducting a study to establish the pharmacokinetics, efficacy and safety of superboosted LPV/r in children in South Africa with the existing ritonavir solution.
The ideal first-line treatment for paediatric HIV would be a protease inhibitor-based all-in-one antiretroviral regimen for HIV-infected children which is a safe and efficacious, is an adapted formulation suitable for infants and children, is an easy-to-use fixed-dose combination, is palatable, addresses drug-drug interaction with medicines for tuberculosis, and is adapted to tropical climates (no refrigeration needed).
By 2019, DNDi aims to deliver from its paediatric HIV portfolio:
- Two new four-in-one paediatric formulations containing a PI (LPV/r) and two NRTIs (ABC or AZT and 3TC)
- One stand-alone paediatric booster RTV for HIV-TB co-infected children
People Living with HIV or AIDS - PLWHA
Infants/Babies (under age 5)
Fosravucoazole (E1224) is a potent orally-available triazole which is under development for Chagas’ disease. Recent evidence suggests that it could be an effective treatment for fungal Mycetoma which would also be affordable. The efficacy of E1224 will be compared to the current treatment (itraconazole) in a randomized controlled clinical trial, examining its effect on moderate mycetoma lesions.
1. Regional R&D:
Short term (2 years) - Prove alternative regimens:
DNDi and partners aim to conduct Phase III clinical trials
proving the efficacy of sofosbuvir (SOF) + daclatasvir
(DCV) as a public health tool in Malaysia and Thailand.
Medium-term (5 years) - Developing a pipeline: License
most promising compounds from patent holders to
combine with other drugs to develop a novel regimen
for HCV to be used as a public health tool.
2. Support affordable access:
Create an actively engaged project Hep C Advisory
Group that can advise the project on the rapidlychanging
HCV treatment access landscape. The
group will be comprised of both Access and
Scientific experts. The project will be both informed
by and inform the project Hep C Advisory Group.
DNDi believes there are many avenues for access
including but not limited to: developing alternative
treatments with favorable licensing / access terms,
patent oppositions, compulsory licensing and
Global Antibiotic Research & Development Partnership (GARDP)
The mission of the Global Antibiotic Research and Development Partnership (GARDP) is to develop new antibiotic treatments addressing antimicrobial resistance and to promote their responsible use for optimal conservation, while ensuring equitable access for all in need. GARDP is being incubated by the Drugs for Neglected Diseases initiative (DNDi) in collaboration with the World Health Organization (WHO) and in support of the Global Action Plan for Antimicrobial Resistance.
A partnership model for product development based on the experience gained from the field of neglected diseases can provide an important element of the overall strategy for R&D in the field of antibiotics. Such a partnership can test new incentives that also contribute to conservation of and access to new antibiotic treatments. By doing so, it can provide an important alternative to the traditional market-driven pharmaceutical approach, by focusing on products that the pharmaceutical industry will likely not develop for lack of profitability.
Launched in May 2016, GARDP is now in its incubation, or start-up phase, hosted by DNDi. This means that until the end of 2017, GARDP will build up its team, establish a legal entity, and set out its long-term strategy and roadmap. In addition, GARDP aims to have at least two projects that address urgent global health needs ready for implementation by the end of 2016, and two more by the end of 2017.
Where we workNew!
Five powerful questions that require reflection about what really matters - results.
SOURCE: Self-reported by organization
What is the organization aiming to accomplish?
What are the organization's key strategies for making this happen?
What are the organization's capabilities for doing this?
How will they know if they are making progress?
What have and haven't they accomplished so far?
DNDi's primary objective is to deliver 16 to 18 new treatments developed with a total investment of EUR 650 million by 2023 and to continue establishing a strong R&D portfolio that addresses neglected patients' needs. In doing this, DNDi wishes to use and strengthen capacities in disease-endemic countries via project implementation and to raise awareness about the need to develop new drugs for neglected diseases and advocate for increased public responsibility.
In the Business Plan for the period 2015-2023, DNDi maintains its commitment to develop treatments for African sleeping sickness, leishmaniasis, and Chagas disease as well as filarial diseases and paediatric HIV. Having transferred its malaria activities to the Medicines for Malaria Venture (MMV), DNDi is also undertaking new research and development (R&D) projects for hepatitis C and mycetoma, two very different diseases that share one key challenge: the existing system of biomedical innovation has failed to deliver safe, effective, quality products that are affordable to poor populations.
The Business Plan 2015-2023 was elaborated through a 24-month process and in-depth consultation with DNDi's founding partners, governments, key stakeholders, and experts in global health research. It was approved by the Board of Directors in June 2015. The new plan emphasizes DNDi's commitment to addressing the needs of neglected patients, while allowing for more flexibility to extend the scope of diseases to address current and future unmet and/or urgent patient needs as they arise. A range of operating and support models has been designed to ensure DNDi's engagement is tailored and appropriate to the need.
DNDi has taken concrete steps to invest in the expansion and development of its Regional Offices, particularly those in neglected-disease-endemic regions. To ensure its activities are carried out in close proximity to the patients who DNDi was created to serve, regional R&D projects, networks of excellence, capacity strengthening programmes, access activities, and advocacy will be taken up increasingly by Regional Offices.
DNDi's budget nearly tripled over the past 8 years. To reach the targeted objectives of the organization, the projected growth for the next Business Plan period will stabilize, reaching approximately 30% over a period of nine years. The dynamic portfolio approach will lead to a balance of investment between the initial disease areas and new programs. Overhead costs will remain low, at approximately 12.5%, other social missions – including advocacy and capacity strengthening – will remain stable at 15%, with the remaining 72.5% for R&D activities.
Upon analyzing its model – including accounting for the attrition rate for drug discovery, development in the field of infectious diseases, and the inherent risk of failure – DNDi estimates the development cost range to be EUR 10-40 million for an improved treatment and EUR 100-150 million for a new chemical entity. These estimations do not include the in-kind contributions from DNDi's many partners.
The 2023 vision relies on an estimated budget of EUR 440 million for the 2015- 2023 period, including EUR 340 million associated to the current portfolio of diseases and activities (with 'other social missions') and EUR 100 million for new opportunities.
As of September 2015, EUR 140 million of the EUR 440 million needed to develop 10-12 additional treatments by 2023 has already been secured. DNDi aims to continue raising unrestricted or portfolio-wide funding and to maintain a balance between public and private sources, with no single donor contributing more than a quarter of the overall budget. It is expected that emerging economies and innovative funding mechanisms will play an increasingly important role in the donor landscape.
The majority of human resources growth will occur in the Regional Offices (80% of new staff), to reach over 210 staff (up from currently 150) by 2023. The ratio of DNDi staff and individuals at other institutions working on DNDi projects will remain stable at approximately 1:4. Building on its 'virtual model', DNDi remains committed to coordination and facilitation roles with partners and stakeholders.
None of the organization's work is possible without the passionate, motivated, and diverse people, spanning public, private, and non-governmental sectors. The people and partners behind the success of DNDi worldwide embody the organization's values in its patient-driven approach, best science and quality for the most neglected, commitment to building partnerships, pragmatism and responsibility, and spirit of entrepreneurship and innovation.
Every four to five years, DNDi reviews and updates its Business Plan in order to ensure the organization stays attuned to current and emerging patient needs. Since its inception, DNDi has advocated for public leadership and a sustainable, publicly-driven framework for essential health R&D. In 2010, a Business Plan review for the period of 2011 to 2018 was conducted, at which time two new disease areas were added to DNDi's portfolio (filarial diseases and paediatric HIV), with a renewed commitment to its core disease activities (human African trypanosomiasis, leishmaniasis, and Chagas disease).
A plan was put in place to complete and transfer malaria activities to partners. The plan also aimed to substantially increase the role of Regional Offices and better define DNDi's engagement in facilitating patient access to treatments.
In 2014, DNDi initiated the process for its next Business Plan to cover the period from 2015 to 2023. Through an extensive consultation exercise involving founding partners and key stakeholders worldwide, DNDi analyzed the R&D landscape, assessed new and emerging R&D gaps, explored the involvement of other players in addressing these needs, and identified future trends. As a result, an adapted decision-making process has been implemented to ensure that the organization remains responsive to neglected patients' needs and the appropriate models were designed.
DNDi has over 30 projects spanning 6 disease areas in their pipeline, including 15 entirely new chemical entities. DNDi works closely with roughly 600 individuals across 130 institutional partnerships, the majority of which are in disease-endemic countries. More than half of the organization's team of 150 staff are in disease endemic countries. As of September 2015, DNDi has raised EUR 350 million equally from public and private sources. Since 2003, DNDi has delivered six new treatments:
- Malaria: 2 two (2) fixed-dose combination (FDC) treatments: artesunate-amodiaquine (ASAQ FDC) and artesunatemefloquine (ASMQ FDC).
- Human African trypanosomiasis: nifurtimox-eflornithine combination therapy (NECT)
- Visceral leishmaniasis in Africa: sodium stibogluconate and paromomycin combination therapy (SSG&PM)
- Visceral leishmaniasis in Asia: a set of therapies, including drug combinations with paromomycin and miltefosine, and liposomal amphotericin B
- Chagas disease: a paediatric dosage form of benznidazole
DNDi has yet to develop a new chemical entity (NCE). To this date, DNDi has successfully relied on two techniques to develop NCEs
- Repurposing compounds for new indications of existing treatments in other diseases (therapeutic switching).
- New combinations of formulations of existing drugs that are better adapted to field conditions and patient needs (paediatric dosage forms, long-acting forms, new route of administration, fixed-dose combinations, co-packaging, or co-administration).
Better Business Bureau Wise Giving Alliance
Drugs for Neglected Diseases Initiative, North America Inc.
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The people, governance practices, and partners that make the organization tick.
as of 2/21/2017
Bennett Shapiro MD
Partner, PureTech Ventures; former Executive Vice President, Merck
Managing Director, External Relations, GAVI Alliance
Instructor, Harvard School of Public Health; Advisor, Medicines Patent Pool; Member, Board of Directors, Doctors Without Borders/ Médecins Sans Frontières (MSF) USA
President, Board of Directors, The Alliance for International Medical Action (ALIMA) USA; former Secretary General, Doctors Without Borders/Médecins Sans Frontières (MSF) International
Executive Director, DNDi
Family Medicine Attending/Teaching Faculty, Residency Program in Family and Social Medicine, Montefiore Medical Center and Family Health Center; Former President, MSF USA
Independent Consultant, global health-related drug discovery and development; former Research & Development Director, DNDi
Partner, PureTech Ventures; former Executive Vice President, Merck
SOURCE: Self-reported by organization
GuideStar worked with BoardSource, the national leader in nonprofit board leadership and governance, to create this section, which enables organizations and donors to transparently share information about essential board leadership practices.SOURCE: Self-reported by organization
Does the board conduct a formal orientation for new board members and require all board members to sign a written agreement regarding their roles, responsibilities, and expectations?
Has the board conducted a formal, written assessment of the chief executive within the past year?
Have the board and senior staff reviewed the conflict-of-interest policy and completed and signed disclosure statements in the past year?
Does the board ensure an inclusive board member recruitment process that results in diversity of thought and leadership?
Has the board conducted a formal, written self-assessment of its performance within the past three years?