The World Health Organization (WHO) has included Fexinidazole Winthrop as the first-choice treatment for the acute form of sleeping sickness in its latest Guidelines for the treatment of human African trypanosomiasis (HAT), updated on 28 June 2024.
Fexinidazole Winthrop is the first oral-only treatment for Trypanosoma brucei (T.b.) rhodesiense sleeping sickness, an acute and lethal form of the parasitic disease found in Eastern and Southern Africa. While most cases of sleeping sickness are caused by the gambiense form of the disease, endemic in West and Central Africa, there have been outbreaks of rhodesiense cases in Malawi and Zambia in 2019-21. A recent localized rhodesiense outbreak in Ethiopia has been linked to climate and environmental changes that bring humans and animals (like cattle) in closer proximity to the tsetse flies that carry the disease.
‘Until today I’ve only been able to use old and very toxic treatments that have to be administered in a hospital under strict surveillance. This is a radical change: I now have a simple oral pill with a demonstrated safety profile to offer my patients. The inclusion of Fexinidazole Winthrop in WHO’s guidelines is a crucial step to ensure patients in places like Malawi can benefit from the new treatment,’ said Dr Westain Nyirenda, physician at Rumphi Hospital in Malawi and site principal investigator of the clinical trial led by the non-profit medical research organization Drugs for Neglected Diseases initiative (DNDi).
Fexinidazole Winthrop is recommended in adults and children six years of age or older, and weighing at least 20kg, of both first-stage (haemo-lymphatic) and second-stage (meningo-encephalitic) of T.b. rhodesiense sleeping sickness.
The treatment was developed by an innovative partnership bringing together Sanofi, DNDi, and the HAT-r-ACC consortium. DNDi conducted a Phase II/III clinical trial in Malawi and Uganda that showed it is an effective alternative to existing drugs. The results led the European Medicines Agency to issue a positive scientific opinion in December 2023, and the regulatory authorities of the Democratic Republic of the Congo to approve its use in June 2024 – which are important steps for endemic countries in Eastern Africa to approve the use of Fexinidazole Winthrop for T.b. rhodesiense and make it available for patients and clinicians.
Sanofi is responsible for the industrial development, registration, production and distribution of the medicine. Fexinidazole Winthrop is donated to WHO by Foundation S, Sanofi’s philanthropic organization.
‘This WHO updated guidance is another step forward for Fexinidazole Winthrop as first oral-only treatment for the acute and lethal form of sleeping sickness. This highlights Sanofi’s continuous commitment to deliver innovative treatments to vulnerable patient communities impacted by sleeping sickness. By working with WHO and DNDi, we have made tremendous progress in improving treatment outcomes and simplifying treatment delivery. This partnership and our donation of Fexinidazole Winthrop through Foundation S reflect our mission to provide innovative treatments to patients, no matter where they live,’ said Philippe Neau, Head of the Neglected Tropical Diseases (NTDs) Program at Foundation S, the Sanofi collective.
Sleeping sickness, or human African trypanosomiasis (HAT), is usually fatal without treatment. It causes neuropsychiatric symptoms, including aggressiveness, psychosis, a debilitating disruption of sleep patterns that have given this neglected disease its name, and ultimately, coma and death. T.b. rhodesiense progresses more rapidly than T.b. gambiense.
‘DNDi’s mission is to deliver innovative treatments to all patients, wherever they are, however neglected they are. Having brought about major therapeutic advances for the more common form of sleeping sickness, we did not want to leave these patients behind even if they are living with a rarer form of the disease,’ said Laurent Fraisse, Research & Development Director at DNDi.
While humans are the main host of T.b. gambiense, T.b. rhodesiense is a zoonotic disease, meaning the infection can spread from animals to humans. Cattle and wild animals such as bushbucks and zebras are the most common known reservoirs for this disease. Movements of these animals – potentially sparked by droughts or changes in climate or land use – could put new populations at risk of T.b. rhodesiense sleeping sickness.
Fexinidazole Winthrop has been registered as the first-line treatment against T.b. gambiense in the Democratic Republic of the Congo (in 2018) and Uganda (in 2021), and has been recommended for use in a further 10 African countries: Angola, Burkina Faso, Central African Republic, Chad, Congo, Côte d’Ivoire, Equatorial Guinea, Gabon, Guinea, and South Sudan. However, it was not recommended for the T.b. rhodesiense form until this year.
Fexinidazole Winthrop has many advantages and does not require intravenous or intramuscular injections, reducing costs both for the health system and for the patients who may access treatment closer to their home, wrote the WHO in its guidelines.
‘Climate and environmental changes could lead to the resurgence of this terrifying disease, so it is crucially important for better and health tools to be in the hands of doctors and patients,’ said Jerome Salomon, Assistant Director-General on Universal Health Coverage and Communicable and Noncommunicable Diseases at the WHO.
The DNDi clinical trial for T.b. rhodesiense was conducted by the HAT-r-ACC Consortium, with funding from the European and Developing Countries Clinical Trials Partnership Association (EDCTP2) programme supported by the European Union (through the grant RIA2017NCT-1846); Fundação para a Ciência e a Tecnologia from Portugal; Swiss Agency for Development and Cooperation (SDC), from Switzerland; Médecins Sans Frontières International; and UK International Development, United Kingdom; and other private foundations and individuals.
About DNDi
The Drugs for Neglected Diseases initiative (DNDi) is a not-for-profit medical research organization that discovers, develops, and delivers safe, effective, and affordable treatments for neglected people. DNDi is developing medicines for sleeping sickness, leishmaniasis, Chagas disease, river blindness, mycetoma, dengue, paediatric HIV, advanced HIV disease, cryptococcal meningitis, and hepatitis C. Its research priorities include children’s health, gender equity and gender-responsive R&D, and diseases impacted by climate change. Since its creation in 2003, DNDi has joined with public and private partners across the globe to deliver 13 new treatments, saving millions of lives. dndi.org
About HAT-r-ACC
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. The consortium partners include the Malawi Ministry of Health (MMoH), the Uganda National Health Research Organisation (UNHRO), the Makerere University in Uganda, Epicentre (MSF) in France, the Lisbon Institute of Hygiene and Tropical medicine (IHMT) in Portugal, the Institut de Recherche pour le Développement (IRD) in France, the WHO, and the Swiss Tropical and Public Health Institute (Swiss TPH).
Media contacts
DNDi
Frédéric Ojardias
+41 79 431 62 16
fojardias@dndi.org
Paul Barasa (in Nairobi)
+254 719 703 195
pbarasa@dndi.org
Photo credit: Lameck Ododo-DNDi
