Development of Acoziborole for the Treatment of Human African Trypanosomiasis

Human African trypanosomiasis (HAT), also known as sleeping sickness, is a life-threatening parasitic disease that is widespread throughout sub-Saharan Africa. HAT spreads through the bite of an infected tsetse fly. In the early stages of infection, parasites in the blood cause mild, nonspecific symptoms. In later stages, the parasites move into the brain, causing severe headaches, disorientation, psychosis, and the characteristic sleep disorders that can lead to coma and death. If left untreated, HAT is fatal. Current treatment varies depending on the stage of infection and requires specialized medical facilities and trained staff, limiting the ability to reach patients in more rural areas. The goal of this project was to develop a single treatment for HAT that is effective in both stages of infection and that will be simpler to dispense, even in resource-limited settings.

Scientific Synopsis

HAT is transmitted by a vector, the tsetse fly, that introduces trypanosomes — free-living extracellular parasites — into the bloodstream, body fluids, and lymph and cerebrospinal fluid. The Trypanosoma brucei species is pathogenic to humans and endemic to sub-Saharan Africa. T.b. gambiense accounts for more than 98% of cases of HAT (gHAT), and T.b. rhodesiense accounts for about 2% of cases (rHAT). The disease progresses through two stages of infection, first in the blood and lymph and then into the central nervous system (CNS). While in the blood and lymph, clinical signs and symptoms are mild and nonspecific, including headaches, fatigue, and intermittent fevers. By contrast, infection in the CNS is marked by pronounced neuropsychiatric signs, including disrupted sleep/wake cycles, hallucinations and aggression, abnormal reflexes, seizures, and coma. When infection has progressed to the CNS, HAT is more difficult to treat, requiring drugs to cross the blood-brain barrier, making early diagnosis and treatment imperative.

Until recently, first-line treatment for late-stage HAT relied on a combination of two drugs (nifurtimox and eflornithine) administered over a course of 10 days, requiring intravenous injection in a clinical setting. To reach wider patient populations in poorer, more remote areas with little health care infrastructure, the lead collaborators developed fexinidazole, an oral therapy taken once daily for 10 days that can treat both early and late stages of infection. To further simplify the treatment regimen, the lead collaborators developed acoziborole, which also treats both stages of infection, but requires only a single oral dose in lieu of a multiday course.

Lead Collaborator

Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland
Laurent Fraisse, Ph.D.

Public Health Impact

HAT mostly affects poor populations in Africa, typically in remote regions outside of major population centers. Endemic to sub-Saharan Africa, 8.5 million people are estimated to be at risk of HAT infection across 37 countries. Current therapies can be too complex to administer in resource-poor areas without sufficient health infrastructure, and left untreated, HAT infection is fatal. Through this project, TRND has opened the door for DNDi to deliver an effective, easy-to-use treatment for this devastating disease.


TRND scientists completed Good Laboratory Practice–compliant nonclinical toxicology studies necessary to support the registration of acoziborole with health regulatory authorities to treat HAT patients in Africa. Phase 2/3 trials have concluded and DNDi is moving toward registration, with agreements from the World Health Organization and Sanofi to provide acoziborole for free to patients through their countries’ public health systems.