The first ever all-oral cure for all stages of sleeping sickness developed by a DFID-funded research programme
Catherine Jeffery, Health Adviser, Research and Evidence Division
Last year, researchers announced a breakthrough: fexinidazole (fexi), the first oral sleeping sickness treatment was approved by the European Medicines Agency. This simple 10-day course of pills is the culmination of ten years public-private partnership by the Drugs for Neglected Diseases initiative (DNDi), with their partners, Sanofi and African research teams, supported by a number of donors including UKAid funding from DFID.
Sleeping sickness is a deadly and neglected disease. It is caused by parasites (Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense) and is called sleeping sickness because patients suffer from sleep disturbances in late stages of the disease, when the parasites cross over into the patient’s nervous system. Patients also experience changes in their behaviour, including aggression and psychosis, confusion, sensory disturbances, poor coordination and ultimately coma. If it is not treated, it is usually fatal within two to three years.
The parasites are spread by the tsetse fly, and the disease is most common in remote and rural areas in sub-Saharan African countries where populations depend on agriculture, fishing, animal husbandry or hunting and have limited access to healthcare. Over 65 million people are at risk of the disease, across 36 countries. In the last year there were 1,447 cases reported, but this may be an under-estimate due to the limited access to healthcare and weak surveillance systems in the affected countries. Over the last 10 years, 70% of cases of disease have been detected in the Democratic Republic of Congo (DRC) with a large proportion of the rest reported in the Central African Republic (CAR). Concerted efforts to control the disease have substantially reduced the number of new cases in recent years and it seems that the elimination of the disease is in sight. However, in the last century several epidemics of sleeping sickness have followed apparent declines in the disease, highlighting the importance of remaining vigilant.
Until relatively recently sleeping sickness was often treated by a toxic drug, that killed one out of every twenty patients. Previously, DNDi and partners developed a new treatment, nifurtimox‐eflornithine combination therapy (NECT), which is safe and effective, but complex to administer, requiring trained staff and well-equipped health facilities. For the patient, treatment requires an unpleasant lumbar puncture procedure to establish the stage of the disease and 14 days in hospital, which includes 56 painful treatment injections in addition to oral drugs.
By contrast, Fexinidazole, is a simple ten-day course of pills. It treats Trypanosoma brucei gambiense sleeping sickness, which accounts for 98% of cases of sleeping sickness and is effective for patients at any stage of the disease. In clinical trials, with people with severe sleeping sickness, it was as effective as the NECT combination therapy and demonstrated good safety for adults and children over six years old. This simple and effective treatment offers the potential to reach and treat many more people suffering from sleeping sickness — a major step towards the elimination of the disease.
The DNDi website showcases a series of film clips of patients explaining the positive impact that the drug has had on their lives.
So how do you discover a molecule, develop a drug, and conduct clinical trials in remote locations of the Democratic Republic of Congo?
Public-private partnerships for developing products to treat diseases, where there is a market failure, are a key feature of the DFID health research portfolio. Fexinidazole is a derivative of a compound first developed in the 1980s by the pharmaceutical company Sanofi. It was ‘rediscovered’ in 2005, by DNDi. DNDi had been searching the compound libraries of pharmaceutical companies, looking for anything with anti-parasitic activity. DNDi collaborated with a range of partners, including the Swiss Tropical and Public Health Institute and the pharmaceutical company, Sanofi, to identify the compound and then develop the drug.
Running clinical trials in the remote and rural settings where sleeping sickness patients live required investigators to overcome challenges such as poor infrastructure, limited laboratory equipment, low levels of clinical research training and political instability. DNDi conducted three clinical trials involving 749 patients in DRC and CAR, funded by public and private donors, including DFID. Use of cars, boats, electricity generators, microscopes, internet, satellites, and the training of 200 people in how to run clinical trials to international standards was required for the Congolese principal investigator Dr Kande, and DNDi, to run the trial and register the drug according to international standards.
The development of Fexinidazole is a great example of the impact that UKAid funded research can have on controlling diseases that affect poor populations across sub-Saharan Africa. From 2019, the new treatment will be available in countries where the disease is present. To have reached this point in the journey towards effective, safe and accessible treatment, and towards elimination of sleeping sickness, is a proud achievement for all involved. As a health adviser in DFID’s Research and Evidence Division, what I find most exciting about Fexinidazole is the great potential if offers to reach the most remote and vulnerable populations who experience the greatest barriers to accessing healthcare.
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