Mentoring organizations:
Sanofi and Drugs for Neglected Diseases initiative (DNDi)
Fellowship highlights:
Development of fexinidazole, the first all-oral drug for sleeping sickness. Fexinidazole distribution in DRC began in January 2020.
Treatments for some neglected tropical diseases (NTDs) have seen a transformation, thanks to the ambition of dedicated scientists and increased political will. For sleeping sickness (Human African Trypanosomiasis), for example, treatments were toxic or cumbersome, and nothing had changed for decades. This prompted Dr Wilfried Mutombo Kalonji to research new treatments. He helped develop fexinidazole, the first all-oral drug for sleeping sickness and a game-changer in the control of the disease.
Wilfried really helped us understand how to conduct the best possible study and how to accommodate our GCP needs in light of the local constraints.
- Dr Nathalie Strub-Wourgaft, Director of Neglected Tropical Diseases, DNDi
Kalonji started this work as a recipient of a TDR Clinical Research and Development Fellowship (CRDF), which placed him as a trainee at Sanofi in Paris for six months from December 2010. There, he learned the theoretical underpinnings of clinical trials – everything from protocol development and site set-up to Good Clinical Practice and regulatory approval. Kalonji went on to spend his second six months with the not-for-profit Drugs for Neglected Disease initiative (DNDi).
The aim of the CRDF is to support researchers from low- and middle-income countries to acquire essential skills in clinical research and development through placements in host training organizations. With this approach, Fellows get a firm grounding in learning how to undertake a clinical trial at a pharmaceutical company before putting those lessons into practice. The combination of working at both Sanofi and then DNDi proved to be critical in developing a new treatment for sleeping sickness.
The challenge in treating sleeping sickness
Sleeping sickness is spread by the bite of the tsetse fly that sends a parasite into the bloodstream, the lymph nodes and the central nervous system. The symptoms include fever and extreme sleepiness during the day and insomnia at night.
Previous treatments were extremely toxic. Melarsoprol, for example, is an arsenic derivative that killed one in 20 patients from toxicity. Later, an improved treatment was a combination of nifurtimox and eflornithine. The problem was that the whole treatment kit weighed 40 kg and had to be sent in large boxes from cities to remote regions where they were needed. In addition, patients had to be in hospital for seven days to receive intravenous infusions of the medicine. This clearly was not a sustainable way to try and eliminate the disease.
Conducting clinical trials in rural Africa
Kalonji and his team at DNDi partnered with Sanofi (who had the patent for the drug) to test fexinidazole in clinical trials in DRC, his home country, and the Central African Republic.
However, they couldn’t just go in and start up clinical trials – in a region with poor infrastructure, they had to set things up from scratch, installing electricity, microscopes, transportation, internet, satellites, and trained staff.
“The reality is the medical reality, the political reality, the environmental reality,” says DNDi’s Dr Nathalie Strub-Wourgaft, who selected Kalonji to be the clinical coordinator of the trial for the duration of his fellowship. “Wilfried really helped us understand how to conduct the best possible study, and how to accommodate our GCP needs in light of the local constraints.” Part of DNDi’s mission, Strub-Wourgaft adds, is to strengthen countries’ capacity in clinical research, and Kalonji’s training surely contributes to that.
She stresses that DNDi, too, has learned from the experience, “by understanding where the patients are, the complexity of their treatment, their nutrition, their whole medical setting – a lot of the things we need to take into account to build a study that works.”
The road to eliminating sleeping sickness
The story of the development of fexinidazole demonstrates how treatment can be transformed when there is a determination to find better solutions. The drug had already been discovered in the 1980s but had been abandoned because of a lack of interest in developing medicines for people who lived in rural parts of Africa. The story of the drug’s development is so extraordinary that DNDi turned it into a film that won the Grand Prix at WHO’s Health for All film festival in 2020.
In 2018, fexinidazole was recommended for approval by the European Medicines Agency and has “changed the lives of patients,” says Kalonji. “We are going from a heavy regimen with more than two weeks of treatment to an easy-to-use treatment that can be used outside of the hospital. It has transformed things for people who can’t access treatment easily.”
Fexinidazole is now being donated by Sanofi to the World Health Organization (WHO) for distribution to national sleeping sickness control programmes in countries where the disease is endemic. In January 2020, fexinidazole distribution began in DRC.
This is especially timely given WHO recently launched the 2030 Neglected Tropical Diseases (NTD) Roadmap, which gives NTDs more global visibility and emphasis, says Kalonji. The push to eliminate sleeping sickness is important because cases of sleeping sickness are declining, and that can give people the false impression that the problem is solved, he says. Focusing efforts on the final stage of elimination is crucial to see it through.
Looking to the future of NTDs
Developing a treatment that is just one pill a day for ten days was a significant achievement, but Kalonji is not content with that. His team at DNDi is now working on developing acoziborole as a single-dose treatment.
Many researchers have had their work affected by the COVID-19 pandemic, and managing a team of scientists who are all working from home is a “new and interesting experience,” he says, especially with four children at home. On top of that, electricity cuts out at random times.
Kalonji and his team are also working on a drug for onchocerciasis that will be tested in clinical trials in DRC and a potential drug for HIV infection in children. While COVID-19 has delayed the onchocerciasis trial by a few months, Kalonji and his team will push ahead with efforts to transform the future of NTDs.