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

Replacing toxic and difficult-to-administer treatments

HAT-r-ACC

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 Stage 2 T.b. rhodesiense sleeping sickness was melarsoprol, a toxic arsenic 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’s control and elimination efforts 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 national sleeping sickness control programmes in Malawi and Uganda to raise awareness of T.b. rhodesiense sleeping sickness among affected communities 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 paves the way for the update of WHO guidelines on treatment for sleeping sickness, and distribution of fexinidazole in African countries where T.b. rhodesiense is prevalent, through Foundation S, Sanofi’s philanthropic organization
Map of Rhodesiense HAT cases in Eastern and Southern Africa (2019-2020)
Cases of human African trypanosomiasis reported from Eastern and Southern Africa (2019-2020). Source: https://doi.org/10.1371/journal.pntd.0010047

T.b. rhodesiense sleeping sickness is a terrifying disease, killing quickly if untreated. Having a simple and safer oral pill to treat this frightening disease will allow doctors to rapidly save lives.’

Dr Westain Nyirenda, Principal Investigator and physician at Rumphi Hospital in Malawi

Project updates

December 2023

The European Medicines Agency’s Committee for Medicinal Products for Human Use has adopted a positive scientific opinion of fexinidazole for the treatment of T.b. rhodesiense sleeping sickness.

2022

With the project entering its final year, the last patient in the clinical trial completed their last visit on 12 October 2022. The trial team began preparing an initial study report before the study was completed to accelerate preparation of the full dossier to be submitted to the European Medicines Agency (EMA) by DNDi industrial partner Sanofi for their opinion on extending the indication of fexinidazole to include treatment for sleeping sickness caused by T.b. rhodesiense. The first scientific article on the ethnographic studies was submitted in December 2022; three additional articles are in preparation. Case detection, training, and communication activities continued throughout the year.

2021

The Phase II/III study to evaluate the safety and efficacy of fexinidazole to treat T.b. rhodesiense sleeping sickness completed recruitment of all patients before the end of the year. The study will continue until the end of 2022 to allow for the follow-up of all patients for 12 months. Additional ethnographic studies were also conducted in Malawi and Uganda to explore the perceptions and practices of local communities and peripheral health centre staff regarding sleeping sickness, to inform interventions to improve rapid case detection and treatment. Posters and leaflets were developed within a large communication campaign to raise awareness of symptoms and the importance of rapid diagnosis and treatment.

2020

DNDi’s Phase II/III study continued in Malawi. In Uganda, the protocol was approved in December 2019, but the study was put on hold due to the COVID-19 pandemic. Recruitment will begin in 2021.

2019

To assess fexinidazole to treat HAT caused by T.b rhodesiense – the other, more virulent subspecies of the parasite affecting humans – a Phase II/III study that aims to enrol 34 stage two patients began with enrolment of the first patient in Malawi in October 2019. A total of 20 patients were enrolled by February 2020.

To provide clinical data to extend the indication to treat rhodesiense sleeping sickness with fexinidazole, we have joined with partners to form the HAT-r-ACC consortium with funding from the European & Developing Countries Clinical Trials Partnership. The consortium is working on a five-year project in Uganda and Malawi, which together account for 88% of rhodesiense sleeping sickness cases globally.

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.

Social science studies

The HAT-r-ACC consortium run two social science studies in Malawi and Uganda to explore the perceptions and practices of local communities and peripheral health centre staff regarding sleeping sickness in order to improve case detection/referral and access to treatment. Read the report from Uganda:

An ethnographic study of local community and peripheral health centre staff perceptions and practices regarding sleeping sickness (r-HAT) to improve treatment access and extend case detection in Uganda

Advocacy posters

Advocacy posters raising awareness about sleeping sickness were developed by the HAT-r-ACC consortium as part of a strategy to improve access to diagnosis and treatment of T.b. rhodesiense sleeping sickness in Malawi and Uganda.

Download advocacy posters for Uganda

Download advocacy posters for Malawi: in Chichewa / in Tumbuka

Presentations at the 10th EDCTP Forum

Strategy to improve access to diagnosis and treatment of rhodesiense human African trypanosomiasis (r-HAT) in Uganda

Sleeping sickness advocacy poster for Malawi

Additional resources

Funding

This project (grant RIA2017NCT-1846) is part of the European and Developing Countries Clinical Trials Partnership Association (EDCTP2) programme supported by the European Union.

EDCTP logo
Supported by the European Union

Other funding:

Fundação para a Ciência e a Tecnologia (FCT) logo
MSF International logo
Swiss Agency for Development Cooperation logo
UK International Development logo

Other private foundations and individuals