Acoziborole is the latest in a series of dramatic improvements in the treatment of sleeping sickness, largely thanks to the work of the Drugs for Neglected Diseases Initiative (DNDi), a Switzerland-based nonprofit. For almost 60 years, the only available drug was melarsoprol, a derivative of arsenic developed in the late 1940s that had such severe side effects it killed one in every 20 patients. In 2009, a regime called NECT that combines two drugs given by infusions and pills was introduced, based in large part on DNDi research. In 2019, NECT was replaced by a drug called fexinidazole, also developed by DNDi—but only for mild and intermediate cases. To distinguish between those and severe cases, doctors check whether the parasite has infected the nervous system, which requires a lumbar puncture, where a needle is inserted into the spinal cord to sample the cerebrospinal fluid.
Because acoziborole can treat both mild and severe forms of the disease, it eliminates the need for this painful and invasive procedure. The pills can be easily transported, allowing them to reach the remote regions most affected by the disease, and health workers don’t have to monitor whether a patient takes a pill each day for 10 days. “It’s a game changer,” says Wilfried Mutombo, a sleeping sickness expert who heads DNDi’s clinical operations in West and Central Africa.
Things could get even simpler in the future. Because current treatments are so complicated, they are given only to people confirmed to have parasites in their blood, a process that requires microscopes and trained technicians—not easy in poor, remote regions—and that misses an estimated 15% of infections. Experts hope acoziborole could be given to all people who test positive on a rapid test for antibodies to the parasite, doing away with the need for microscopy. Mutombo is currently helping lead a clinical trial of 2500 people in the DRC to test whether acoziborole administration based on antibody tests is safe and lowers transmission rates. (Another trial is testing the treatment in children under age 14.)
DNDi researchers discovered the compound that gave rise to acoziborole in a library of potential drugs developed by Anacor Pharmaceuticals, a California biotech acquired by Pfizer in 2016. Scientists modified it so it more effectively reached the brain, and phase 1 trials in France showed it was safe in humans. A phase 2/3 clinical trial in 208 patients in Guinea and the DRC, published in 2022, showed the drug cured all mild and intermediate cases and 95% of severe cases. Side effects were generally mild, with headache the most common.
Sanofi, which has worked with DNDi on sleeping sickness treatments for 2 decades, helped coordinate the application to EMA, which reviewed it under a special procedure for drugs intended for use outside the European Union. Today’s “positive opinion” opens the way for countries like the DRC to approve its use and for WHO to add it to its list of recommended treatments. Sanofi will donate the drug to the agency for distribution, and it will be free for patients.
Acoziborole could help WHO reach its goal to drive T. brucei gambiense, which primarily infects humans, to extinction. (T. brucei rhodesiense rarely infects humans and is mostly found in wild animals, which makes it very unlikely that it could be completely eradicated.)
Still, experience with other diseases shows eradication is hard. As a disease becomes more and more rare, both health workers and community members are less likely to recognize it, and undiagnosed cases can continue to spread the pathogen. The symptoms of sleeping sickness may make things even more difficult. “This is a disease that looks like spirits attacking you, alcoholism, PTSD [post-traumatic stress disorder], or malaria, and these are things that don’t always prompt people to go to a health center,” Palmer says. Continuing screening programs and ensuring treatment is available, even when infections become extremely rare, is crucial, she says.
Despite those challenges, “We need to go for elimination,” says Lejon, who is assisting with the ongoing trial in the DRC. “With acoziborole, we can really do it.”
