Fexinidazole: a chink in the armor of human African trypanosomiasis

Human African trypanosomiasis (HAT) is a life-threatening neglected tropical endemic disease (NTD) in Sub-Saharan Africa caused by subspecies of the protozoan parasite Trypanosoma brucei and transmitted through tsetse flies. Few therapeutic options are available for this pathology, and most of them require a skilled professional, as they have to be administered intravenously. Additionally, they are usually associated with severe adverse outcomes. Notably, in 2018 and 2021, fexinidazole was approved by the European Medicines Agency (EMA) and the United States Food and Drug Administration (U.S. FDA), respectively, as the first all-oral treatment for both the first and second stages of the disease. This chapter aims to present an overview of the discovery, development, and approval of this drug. Special emphasis is placed on the clinical trials conducted that have evidenced the efficacy and safety of fexinidazole.