Historic Breakthrough in Sleeping Sickness: FDA Approves Fexinidazole, the First All-Oral 10-Day Treatment Developed by Sanofi and DNDi

Sleeping sickness (Image source: Focus Medica)

July 20, 2021 /BioonBIOON/ -- Sanofi recently announced that the U.S. Food and Drug Administration (FDA) ApprovedFexinidazole, as the first all-oral treatment, is indicated for patients aged 6 years and older weighing at least 20 kg for the treatment of both stages of Trypanosoma brucei gambiense sleeping sickness.(human African trypanosomiasis, HAT, human African trypanosomiasis). Fexinidazole is a 5-nitroimidazole derivative and a DNA synthesis inhibitor, representing the first all-oral treatment for human African trypanosomiasis (HAT or sleeping sickness).

Sleeping sickness is a parasitic disease., this is a fatal neglected tropical disease,Transmitted by the bite of infected tsetse flies (tsetse fly, tsetse fly).This disease 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 always fatal. Sleeping sickness 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 that fexinidazole is accessible in all countries where sleeping sickness is endemic.

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

Fexinidazole is indicated for: use as a 10-day, once-daily regimen for the treatment of Human African trypanosomiasis caused by Trypanosoma brucei gambiense.This is the most common form of sleeping sickness, 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, during which parasites cross the blood-brain barrier and cause neuropsychiatric symptoms in patients.Therefore, fexinidazole can eliminate the need for routine hospitalization and potentially reduce the number of lumbar punctures.

Chemical structure of fexinidazole (Image source: chemdiv.com)

Fexinidazole is a 5-nitroimidazole derivative initially developed by Hoechst (a predecessor of Sanofi) in the 1980s but later abandoned for strategic reasons. During a search for compounds with antiparasitic activity by the non-profit research and development organization Drugs for Neglected Diseases initiative (DNDi), the drug was identified in 2005 in collaboration with the Swiss Tropical and Public Health Institute. In 2009, DNDi partnered with Sanofi, the patent holder of fexinidazole, to resume development of the drug for the treatment of sleeping sickness. Under this collaboration, DNDi is responsible for preclinical, clinical, and pharmaceutical development, while Sanofi handles industrial development, regulatory registration, manufacturing, and commercialization of the product.

Fexinidazole was developed as part of an innovative partnership with DNDi, which conducted the drug's keyClinical Trial, and collaborates 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 trials conducted by DNDi,Fexinidazole demonstrated high efficacy and safety across both stages of the disease in adult and pediatric patients aged ≥6 years and weighing ≥20 kg.

Sleeping Sickness - Tsetse Fly (Image source: nigeriagalleria.com)

It is worth noting that,Following FDA approval, DNDi was awarded a Tropical Disease Priority Review Voucher (PRV).。FDAThe 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 arising from the PRV., which will enable both parties to continue investing in innovation and ensure access to new tools for treating sleeping sickness and other neglected diseases. As part of a long-standing collaboration with the WHO, Sanofi has pledged to continue providing 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 has now become a reality. This drug was developed by us and Sanofi in close collaboration with 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. Twenty years ago, the company launched an ambitious partnership with the World Health Organization to jointly combat neglected tropical diseases. Following the positive scientific opinion issued by the European Medicines Agency (EMA) at the end of 2018,FDAThe approval is a crucial step in revitalizing efforts to support the sustained elimination of this disease." (Bioon.com)

Source:FDA approves fexinidazole as the first all-oral treatment for sleeping sickness