Sleeping sickness A trial in Africa found fexinidazole to be 91% effective at treating sleeping sickness. Though less effective than
nifurtimox with
eflornithine in severe disease, fexinidazole has the benefit that it can be taken by mouth.
Efficacy and safety In cell culture, fexinidazole has an
IC50 of around 1–4 μM against
Trypanosoma brucei. In the mouse model, fexinidazole cures both the first, hemolymphatic, and the second, meningoencephalitic stage of the infection, the latter at 100 mg/kg twice daily for 5 days. In patients, the clinical trials managed by DNDi and supported by Swiss TPH mainly conducted in the
Democratic Republic of the Congo demonstrated that oral fexinidazole is safe and effective for use against first- and early second-stage sleeping sickness. Based on the positive opinion issued by the European Medicines Agency in 2018, the WHO has released new interim guidelines for the treatment of HAT including fexinidazole as the new therapy for first-stage and non-severe second-stage sleeping sickness caused by
Trypanosoma brucei gambiense (gHAT) Recently, a study of the safety and efficacy of oral fexinidazole in children with gambiense human African trypanosomiasis was accomplished and concluded that orally administered fexinidazole showed high efficacy across all stages of gambiense human African trypanosomiasis infection in children aged 6 years and older and weighing more than 20 kg. The benefit-to-risk ratio of fexinidazole for treating children with gambiense human African trypanosomiasis, regardless of disease stage, is positive. Current interventions for diagnosing, staging, and treating gambiense human African trypanosomiasis require resources, trained personnel, equipment, and hospital infrastructure. These potentially costly procedures are therefore difficult to implement in remote areas or in those that might be mired in conflict, which could prevent the goal of eliminating gambiense human African trypanosomiasis by 2030. Simplified oral treatments such as fexinidazole or single-dose oral treatments such as
acoziborole (currently in clinical trials) that can cure both disease stages of gambiense human African trypanosomiasis and circumvent the need for systematic disease staging with lumbar puncture (a procedure associated with complications and anxiety, particularly in children) would benefit both patients and health-care professionals Furthermore, Damasio
et al. evaluated the
in vivo oral efficacy of self-emulsifying drug delivery systems (SEDDS) containing fexinidazole in the experimental treatment of visceral leishmaniasis (VL). The developed FEX-SEDDS formulation presented as a clear, yellowish liquid without precipitate. In the simulated gastric and intestinal media, the FEX-SEDDS had a size of 97±1 and 106±9 nm, respectively. The FEX retention in droplets after SEDDS dilution in simulated gastrointestinal media was almost 100%. Antileishmanial efficacy studies showed that FEX-SEDDS was the only treatment able to significantly (p < 0.05) reduce the parasite burden in the liver and spleen of animals experimentally infected with
Leishmania infantum. ==Mechanism of action==