Eight New Treatments For World’s Most Neglected Diseases: DNDi’s Pécoul Reflects On Milestones At 15 Year Mark

The Drugs for Neglected Diseases Initiative (DNDi) celebrates its 15th anniversary this week, as a non-profit drug R&D organization that sought to create an alternative model for developing drug treatments for the most neglected diseases and the world’s poorest populations. Since DNDi’s launch in 2003, the organization has developed eight new treatments, including the first-ever oral drug for sleeping sickness, fexinidazole. Executive Director Dr Bernard Pé‏‏‏coul, who has guided the organization since its creation in 2003, looks back on the mission and its progress.

Dr Pécoul holds the malaria treatment artesunate and amodiaquine (ASAQ), DNDi‘s first treatment successfully brought to market.

Health Policy Watch: You are celebrating the 15th anniversary of DNDi.  How did DNDi come about and what gap has it filled in the R&D landscape?

Bernard Pé‏‏‏coul: We were created in 2003 and started operations in 2004 based on an assessment that the R&D for neglected diseases was totally abandoned. At the time I was director of [the Médecins Sans Frontières (MSF) Campaign for Access to Essential Medicines]. We documented this imbalance in a publication, saying that it’s time to create a different model, at the time the gap was big, and they were trying to find other solutions. The three gaps we documented included:

  1. The lack of new drug candidates. So [in DNDi] we created a consortium to not only screen [candidate molecules] but also to lead optimization [of those molecules] until we have clear chemical entities ready to enter into clinical development.  In our portfolio we [now] have 22 chemical entities in this process, some led by us and some by other partners as leads.
  2. Barriers to clinical development. Typically, the private sector was not ready to enter these complicated clinical settings. This is really the phase in which DNDi is very active.  Typically, we are in charge of the clinical development, and we develop most of the phase 2 and phase 3 studies. We are not alone because we always work in partnership with institutions at the country level, with global health, institutions. At the same time, we try to secure a partnership with Pharma, or with several pharma companies, as this is also a phase where we need to consolidate industry partners for the next phase – which is registration of the product and distribution. So, while we collaborate with pharma to identify the molecules, we “de-risk” pharma because we oversee the clinical studies.
  3. The gap between product and treatment. There is a still a gap at the end of the pipeline, or a lack of incentives to complete the development of new formulations in ways that are more adapted to the field. This means combining creating formulations for children or combining drugs into fixed-dose formulations, which is what we did for malaria. That’s why we talk about treatments and not products.  Our objective is to respond to patient needs, and treatments respond better than products.

HP-Watch: Can you summarize the 3-4 biggest breakthroughs you have experienced in drug development – up to the recent approval of the new drug fexinidazole for sleeping sickness?

Pécoul: Fexinidazole was the first time we developed a product from beginning to the end. The previous successes have been improving new drugs from new formulations.  Altogether there have been another 7 initial treatments that we developed.

The first breakthrough was a malaria treatment combining [the two most effective malaria drugs]. We completed development of that in 2007, with registration and prequalification, and in the last 10-12 years more than 500 million people have received this this treatment in Africa. Our partner in this was Sanofi; they accepted non-exclusivity in the contract, so that there are also generic companies producing the combinations.

Then there was a new formulation for children for Chagas disease [a chronic and disabling disease transmitted by the triatomine bug in Latin America]. Many children are affected, but when we entered this portfolio, the only formulation available was an adult formulation. We were not able to deliver a proper dose for children affected with Chagas. [People would have to split the pill into pieces]. We partnered with pharma companies in Brazil and in Argentina to devise two sources of a paediatric formulation.

A child with HIV takes a paediatric dose of antiretroviral medication, a formulation which DNDi developed.

Then, we achieved something similar in developing paediatric formulations [of antiretroviral drug combinations] for HIV. The existing formulations could be very difficult to take, or they would need special handling, such as refrigeration. So, we are developing a new formulation adapted to kids that was just submitted to the US Food and Drug Administration (FDA) in October this year.  That is a four-in-one combination of the first-line drugs recommended by WHO, but for which today there is no formulation adapted to the kids. We have done this in partnership with the Indian-based generic company CIPLA.  This required a lot of research work, going back to pre-clinical studies.

HP-Watch: What are the key lessons you think have been learned from DNDi’s model, in terms of:  sustainable financing, ensuring more returns on public investments, an end to end approach?

Pécoul: We are releasing today a “model paper”, [a report] on lessons we have learned over our 15 years.  These include lessons about how to facilitate the regulatory process; on how important it is to be very strongly linked with governments and to have public leadership on R&D reflecting commitment from the affected country; and the importance of target [drug candidate] profiles. I think having access [and therefore affordability] in mind from the beginning is very important, this influences your choice of partners but also the candidates you will develop.

Because we are a not-for-profit, and we position access as a key element of our investment, we are trying to develop public goods (i.e. generics) as much as possible. This means that the fruit of the innovation will go back to the public at an affordable price.  The return on investment is more about benefits for the population.  At the same time, because we are not making any profit from what we invest, we have very few mechanisms to secure sustainable funding.

When we are investing on treatments for very neglected populations, so the opportunities to establish sustainable funding to finance our investments are very few:  the populations we serve, by definition, have no purchasing power.

you had stable insulin that you could use in tropical conditions, this would be an interesting innovation.

HP-Watch: So, are you looking at some aspects of NCDs as another future gap or opportunity?

Sample preparation at bio-repository CEADES-DNDi, a partner for DNDi’s clinical studies on Chagas in Bolivia

Pécoul: Not for the time being, but we are not closing the door.  A few years ago, we revisited our mission statement, and we talk about neglected populations [a broader concept than neglected diseases]. But at DNDi we have so far not had the capacity to respond to the big issue of access. We have tried to demonstrate that a different R&D model could work. But we are not the only solution to the problem of innovation and access.

HP-Watch: At the same time, with regards to R&D costs, DNDi’s assessment of its own R&D experiences indicates that costs are not necessarily as high as some of the industry estimates that are out there.  Can you describe and explain why the gap is so high?

Pécoul: We have estimated the cost of improving the treatment of existing drugs to be on the order of US$ 10-30 million. When we talk about developing wholly new chemical entities from scratch, and including attrition, then we are more talking about US$ 60-200 million. True, we are still far away from the US$ 2 billion [quoted by pharmaceutical industry sources].

But we need to be careful about comparing things that are not comparable. We are developing treatments in a field that is very abandoned; we [only] must demonstrate superiority against treatments that are very bad.

Much of the new research is industry documenting that their drug is slightly better than the previous one, and that is very costly. Most of the big companies have abandoned the field of communicable diseases. Secondly industry includes their opportunity costs or costs of capital for investing for years in a product. What we calculate is the real cost of developing. So, the way that we calculate is not the same.

The DNDi model is more cost-effective because it is tailored to achieving the goal that we are trying to pursue. But I don’t think that we could expect that a large pharma company would do the job [in the same way]. What we have achieved is to get a lot of support and commitment from [big] Pharma to pursue our goal.

HP-Watch: What challenges lie ahead?  Do you see DNDi continuing to address infectious diseases only, or could NCDs also be a target, insofar as they are an increasingly large proportion of the burden in LMICs but receive very little investment for treatments geared to low-income populations.

Pécoul: We still have a big challenge with leishmaniasis, it is very prevalent in many parts of the world, and we still use old products that are very difficult to use. We have identified a series of new chemical entities and we want to complete the development of an oral treatment for leishmaniasis. [As of now, there are no all-oral treatments.].

HP-Watch: Are there diseases that might be ripe for elimination?

A doctor dispenses fexinidazole, the first-ever oral treatment for sleeping sickness, which was developed by DNDi.

Pécoul: The best example is sleeping sickness. Fexinidazole, the new oral treatment developed for DNDi in 2018 is taken for 10 days, and is already a massive improvement on early options. But we have one project in the portfolio [pipeline] that would be a single dose treatment for sleeping sickness. If we are successful in developing a single dose, we could be successful in eliminating the Gambiense form of the disease, which is the most common one, and where the reservoir is primarily other human beings, although tsetse flies are vectors.

HP-Watch: What about malaria? Can you explain your involvement with that disease?

Pécoul: We were involved initially in malaria, where we developed two combination dose formulations, as mentioned.  But we completed the job and then transferred to Medicines for Malaria Venture.  They are a close partner of MMV, and they continuing to monitor these projects.

HP-Watch: And other disease frontiers where you see DNDi playing a role?

Pécoul: We will remain focused on NTDs, but not exclusively. For instance, in the last few years we have worked on paediatric formulations for HIV, and we also worked on adult medications for hepatitis C. We could at some point include some NCDs or other issues. For instance, there is the issue of snakebites. It is a neglected disease area.

But in all choices, we would have to assess the needs and the science to see if the scientific background is there to create the basis for success. We are not going back to basic research and we also must look if others are better positioned to do the job.

Concerning antimicrobial resistance, together with WHO we helped incubate GARDP, in which we are trying to use the model of DNDi to develop a new generation of treatments for AMR.

HP-Watch: Recently, DNDi worked with the European Medicines Agency [EMA] to make use of a special section of its regulatory code, known as “Article 58” to help fast-track regulatory approval of the new drug for sleeping sickness, fexinidazole, bringing African regulatory authorities into the process. Can you describe why that process represents a precedent that can help get new treatments to patients more rapidly?

Pécoul. Article 58 is an agreement between WHO and EMA, and in this agreement EMA reviews a dossier for a product that will be used outside of Europe, and they agree to include regulatory authorities from the countries involved.  So, in this case, representatives of the Democratic Republic of Congo (DRC), [which is one of the primary areas affected by sleeping sickness], were involved. That, in turn, helped expedite the national regulatory process, since DRC representatives sat on the EMA body that approved the drug. It’s a good example of collaboration on regulatory issues.


Dr Bernard Pécoul has led the Drugs for Neglected Diseases initiative (DNDi) since its founding in 2003. Under his guidance, DNDi – a not-for-profit research and development organization – with hundreds of public and private partners, has delivered eight new treatments for the most neglected diseases (leishmaniasis, sleeping sickness, and Chagas disease) and for malaria. It has developed a robust portfolio of projects spanning from discovery to implementation for these diseases as well as filaria, paediatric HIV, mycetoma, and hepatitis C. As part of DNDi’s dynamic portfolio approach, Dr Pécoul also led the creation with WHO of GARDP, a new product development partnership to address R&D for new antibiotic treatments.

DNDi aims to deliver a total of 16 to 18 new treatments for neglected patients by 2023. The initiative, through its R&D work, also builds capacity in disease endemic countries through research platforms and technology transfers and advocates for greater public leadership to sustainably address the health needs of neglected patients.

Prior to DNDi, Dr Pécoul was Director of the Médecins Sans Frontières (MSF) Campaign for Access to Essential Medicines from 1998 to 2003, a position he took on after that of Executive Director of MSF-France. While working with MSF, Dr Pécoul carried out field missions in Africa, Latin America, and Asia. In 1988, he co-founded Epicentre, an MSF-affiliated NGO specialized in epidemiology.

Image Credits: Paul Kamau/DNDi, FBBVA, Ana Ferreira/DNDi, Xavier Vahed/DNDi.

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