Sanofi Announces FDA Approval of Fexinidazole as First All-Oral Treatment for Both Stages of Trypanosoma brucei gambiense Human African Trypanosomiasis

Sleeping sickness (Image source:Focus Medica）

SanofiSanofi recently announced that the U.S. Food and Drug Administration (FDA) has approved fexinidazole as the first all-oral treatment for patients aged 6 years and older weighing at least 20 kg, for the treatment of both stages of human African trypanosomiasis (HAT, sleeping sickness) caused by *Trypanosoma brucei gambiense*. Fexinidazole is a 5-nitroimidazole derivative and a DNA synthesis inhibitor, and is the first all-oral formulation for the treatment of human African trypanosomiasis (HAT or sleeping sickness).

Sleeping sickness is a parasitic disease and a fatal neglected tropical disease transmitted through the bite of infected tsetse flies. It primarily affects populations living in remote rural areas of sub-Saharan Africa, where approximately 65 million people are at risk of infection. If left untreated, sleeping sickness is almost invariably fatal. The disease causes neuropsychiatric symptoms, including a debilitating disruption of sleep patterns, uncontrollable aggression, and psychosis. Through collaboration with Sanofi, the number of sleeping sickness cases reported to the World Health Organization (WHO) decreased by approximately 97% between 2001 and 2020. DNDi, Sanofi, and their partners are committed to ensuring access to fexinidazole in all countries where sleeping sickness is endemic.

Although current treatment regimens for sleeping sickness are effective, the need for intravenous infusion or injection and hospitalization imposes a heavy burden on patients and healthcare workers, posing even greater challenges for those living in remote areas.

Fexinidazole is indicated for: use as a once-daily, 10-day treatment for sleeping sickness caused by Trypanosoma brucei gambiense. This is the most common form of sleeping sickness and is found in West and Central Africa. Importantly, fexinidazole is the first all-oral treatment indicated for both stage 1 (early stage) and stage 2 of the disease, when the parasite has crossed the blood-brain barrier and causes neuropsychiatric symptoms in patients. Therefore,fexinidazoleCan eliminate the need for routine hospitalization and potentially reduce the number of lumbar punctures.

fexinidazoleChemical Structure (Image Source:chemdiv.com）

     fexinidazoleis a type of5-Nitroimidazole derivatives, originally byHoechst(Predecessor of Sanofi) in20Century80Developed in the [decade/era], later abandoned due to strategic reasons. In non-profit research and development organizations“Drugs for Neglected Diseases Initiative (DNDi）”During the search for compounds with anti-parasitic activity, the drug was2005Determined in collaboration with the Swiss Tropical and Public Health Institute in [year].2009Year,DNDiand possessfexinidazoleIn collaboration with Sanofi on the patent, research on the drug was restarted for the treatment of sleeping sickness. Among them,DNDiResponsible for preclinical, clinical, and pharmaceutical development, while Sanofi is responsible for the industrial development, regulatory registration, manufacturing, and commercialization of the drug.

     fexinidazoleAs andDNDideveloped as part of an innovative partnership between [entities], and the organization conductedThe key to this drugClinical Trial, and collaborated with the National Sleeping Sickness Programs of the Democratic Republic of the Congo (DRC) and the Central African Republic (CAR), as well as Sanofi.

On November 16, 2018, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive scientific opinion on fexinidazole. In clinical studies conducted by DNDi, fexinidazole demonstrated high efficacy and safety across both stages of the disease in pediatric patients aged ≥6 years and weighing ≥20 kg, as well as in adult patients.

Sleeping sickness-Tsetse fly (Image source:nigeriagalleria.com）

Notably, following FDA approval, DNDi was awarded a Tropical Disease Priority Review Voucher (PRV).The FDA Tropical Disease Priority Review Voucher (PRV) Program was established in 2007 to incentivize the development of new therapies for neglected tropical diseases, including sleeping sickness. Sanofi and DNDi will share any benefits derived from the PRV, enabling both parties to continue investing in innovation and ensuring access to new tools for treating sleeping sickness and other neglected diseases. As part of its long-standing partnership with the WHO, Sanofi has committed to continuing to provide the drug free of charge to the WHO for distribution to affected countries.

Dr. Bernard Pecoul, Executive Director of DNDi, said: "For frontline clinicians, a simple, all-oral treatment for sleeping sickness is now a dream come true. This medicine was developed through close collaboration between us, Sanofi, and researchers in countries heavily affected by sleeping sickness. We are proud of this latest milestone in our long-standing partnership with Sanofi."

Luc Kuykens, Senior Vice President of Sanofi Global Health, stated: “This FDA approval marks a significant milestone in Sanofi’s long-standing commitment to combating sleeping sickness, as 20 years ago, the company and the World Health Organization established an ambitious partnership to jointly fight neglected tropical diseases. Following the positive scientific opinion issued by the European Medicines Agency (EMA) at the end of 2018, the FDA approval reinvigorates efforts to support continued...”An important step toward eliminating this disease”。