A tsetse fly bite can transmit the parasite that causes sleeping sickness, a disease that can progress from mild symptoms to death within weeks if untreated. A new drug, acoziborole, has received a positive opinion from a committee of the European Medicines Agency and could be in use by early next year, offering a major advance toward the World Health Organization’s goal of eliminating the disease by 2030.
Acoziborole is taken as three pills swallowed together in a single dose, replacing older treatments that required intravenous administration and caused severe reactions, including a burning sensation in the veins and a roughly 5% fatality rate in some cases. The current oral first-line treatment, fexinidazole, must be taken for 10 days and can cause nausea, vomiting and heart-rhythm disturbances. Clinical trials of acoziborole reported only one significant side effect: mild to moderate headache.
Dr. Gerardo Priotto, who leads WHO’s efforts against sleeping sickness, notes that past therapies were difficult to use because they required staff, equipment and reliable infrastructure—barriers especially acute in the remote, rural areas where most cases occur. Dr. Stéphane Hugonnet of the Drugs for Neglected Diseases Initiative (DNDi), which developed the drug with Sanofi and partner funding, says harsh side effects of earlier medications discouraged people from seeking care.
The parasite Trypanosoma brucei gambiense causes more than 90% of cases and is the target of acoziborole. The illness has two phases: an early stage with fever and headaches, and a later stage after the parasite crosses the blood-brain barrier, producing neurological effects such as confusion, convulsions and disruption of sleep-wake cycles—patients become sleepy by day and awake at night. Without treatment, the disease can lead to coma and death. Acoziborole treats both stages.
Sleeping sickness largely affects poor, rural populations in warm savanna woodlands and vegetation along lakes and streams where tsetse flies thrive. Sustained control efforts—tsetse fly control, diagnostic testing and treatment—have drastically reduced cases from hundreds of thousands historically to about 1,000 annually today, with nearly two-thirds in the Democratic Republic of Congo (DRC). Yet the disease has historically ebbed and resurged.
Dr. Wilfried Mutombo Kalonji of DNDi calls acoziborole “transformative,” and DNDi has been working since 2003 to develop treatments for neglected diseases neglected by market-driven pharmaceutical R&D. Kalonji, who helped lead clinical trials in South Ubangi province in the DRC, is now overseeing research to determine whether serologic blood tests could allow immediate treatment rather than waiting for confirmatory tests that are slower, more expensive and often unavailable in the field.
Monica Mungier of Johns Hopkins notes that the parasite can sometimes evade detection, so negative tests don’t always rule out infection. But if blood tests prove reliable for guiding care, testing and treatment could start the same day, increasing the number of patients treated and reducing the human reservoir that sustains transmission.
Next steps include review of acoziborole by the DRC Ministry of Health and by WHO to consider updating treatment guidelines, which would help other countries authorize its use. Global health experts caution that cuts to U.S. and Western funding could hinder access to the drug in countries that need it most.
Much of the progress toward elimination depends on African researchers and trial participants working under difficult conditions—remote locations often lacking electricity, water and infrastructure. Trial teams had to set up facilities, train health workers and provide connectivity and safe transport to testing sites. Researchers say these challenges were overcome through concerted effort.
If acoziborole scales up alongside improved testing and sustained support for control programs, the single-dose, well-tolerated treatment could markedly simplify care, expand access in remote areas, and accelerate efforts to eliminate sleeping sickness.