Highly effective and safe all-oral cure for an acute and lethal form of sleeping sickness

Replacing toxic and difficult-to-administer treatments

Fexinidazole, the first all-oral drug for sleeping sickness, also known as human African trypanosomiasis (HAT), was developed in clinical trials led by DNDi. It was added to the World Health Organization’s List of Essential Medicines for adults and children in July 2019 and was initially only indicated as a treatment for T.b. gambiense sleeping sickness, the most common form of the disease.

Less common, T.b. rhodesiense sleeping sickness is an acute form of the disease, occuring primarily in Eastern and Southern Africa. T.b. rhodesiense sleeping sickness progresses more rapidly than T.b. gambiense sleeping sickness, and often causes death within weeks or months if untreated.

In 2018, DNDi joined with partners (see below) to form the HAT-r-ACC consortium to provide clinical data to assess the use of fexinidazole as a treatment for both stages of T.b. rhodesiense. Better treatment for T.b. rhodesiense sleeping sickness was needed: the only treatment available for advanced T.b. rhodesiense sleeping sickness was melarsoprol, a toxic arsenic-based drug dating from 1940s, that contributed to the death of up to 10% of patients it was meant to cure. While the treatment option for Stage 1, suramin, was less toxic, it was difficult to administer, requiring five intravenous injections given every seven days for over a month. 

Starting in 2019, DNDi led a Phase II/III study in Malawi and Uganda to provide evidence to extend the indication for fexinidazole to T.b. rhodesiense and support WHO efforts to control and eliminate the disease as a public health problem in Eastern Africa. When the project began, Malawi and Uganda accounted for 93% of T.b. rhodesiense cases globally. Data from the study showed that fexinidazole is highly effective in treating T.b. rhodesiense and is a safe alternative to the existing drugs.  Following these results, the European Medicines Agency’s Committee for Medicinal Products for Human Use adopted a positive opinion of fexinidazole for the treatment of T.b. rhodesiense in December 2023.

The HAT-r-ACC consortium also supported ethnographic research that led to the development of adapted communication materials to raise awareness of T.b. rhodesiense sleeping sickness among affected communities in Malawi and Uganda and increase early detection of cases.

DNDi’s long-term goal for sleeping sickness is to develop and register two new drugs that are effective against both Stage 1 and Stage 2 of the disease and both subspecies of the parasite, T.b. gambiense and T.b. rhodesiense.

Treatments regimens

• Indication: Stage 1 and Stage 2 T.b. rhodesiense sleeping sickness (human African trypanosomiasis)
• Dosage: 10-day, once-daily oral treatment

Impact

• The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion of fexinidazole for the treatment of T.b. rhodesiense in December 2023
• The CHMP opinion also paves the way for the distribution of fexinidazole in African countries where T.b. rhodesiense is prevalent, through Foundation S, Sanofi’s philanthropic organization
• WHO treatment guidelines changed in 2024 to recommend fexinidazole as first-line treatment for T.b. rhodesiense sleeping sickness
• Approved for treating T.b. rhodesiense sleeping sickness by Democratic Republic of Congo (DRC) in 2024

HAT-r-ACC consortium

The HAT-r-ACC consortium brings together a broad range of partners with expertise in sleeping sickness and capacity building in remote health settings. This research, training, and community engagement experience is essential to run the clinical trial in remote settings with a very small target population.