Fexinidazole: First Global Approval.

Fexinidazole Winthrop (hereafter referred to as fexinidazole) is a DNA synthesis inhibitor developed by the Drugs for Neglected Diseases initiative (DNDi), in collaboration with Sanofi, for the oral treatment of human African trypanosomiasis (HAT) [commonly known as 'sleeping sickness'] and Chagas' disease. The drug is a 5-nitroimidazole derivative first discovered by Hoechst AG (now part of Sanofi) and was identified by the DNDi in 2005 as having activity against Trypanosoma brucei gambiense and T. b. rhodesiense. Under Article 58 of Regulation (EC) no. 726/2004 (a regulatory mechanism for reviewing new medicines destined for use outside of the EU), fexinidazole has been granted a positive opinion by the EMA for the treatment of both the first-stage (haemo-lymphatic) and second-stage (meningo-encephalitic) of HAT due to T. b. gambiense (g-HAT) in adults and children aged ≥ 6 years and weighing ≥ 20 kg. This approval will facilitate and support marketing authorization application in endemic countries in 2019; following registration, fexinidazole will be distributed via the WHO to endemic countries for g-HAT. Phase 3 evaluation of fexinidazole for g-HAT is ongoing in the Democratic Republic of the Congo and Guinea and the drug is also in development for Chagas' disease, with a study currently ongoing in Spain. Clinical development for visceral leishmaniasis is discontinued. This article summarizes the milestones in the development of fexinidazole leading to this first approval for g-HAT.