By Atieno Mboya  

World Health Organization’s ambitious target of eliminating sleeping sickness as a public health problem by 2020, could be realized after European Medicines Agency’s Committee for Medicinal Products for Human Use approved fexinidazole, as the first all-oral treatment for sleeping sickness. The drug will support international efforts to eliminate sleeping sickness, a fatal neglected tropical disease endemic or confined to Africa.

Fexinidazole is indicated as a 10-day once-a-day treatment for Trypanosoma brucei gambiense sleeping sickness which is the most common form of the disease, found in West and Central Africa.

It is the first all-oral treatment that works for both for the early stage of the disease and second stage of the disease in which the parasites have crossed the blood-brain barrier, causing patients to suffer from neuropsychiatric symptoms.

The majority of sleeping sickness patients are reported in the Democratic Republic of Congo, where 78% of Trypanosoma brucei gambiense sleeping sickness cases were reported in 2017, followed by the Central African Republic, Guinea, and Chad.

Clinical trials involved 749 patients in the DRC and Central African Republic. Fexinidazole showed high efficacy and safety in both stages of the disease in adults and children over six years and weighing above 20 kg. Fexinidazole could eliminate systematic hospitalization and also the number of lumbar punctures.

“Fexinidazole is an entirely new chemical entity that has been developed through an alternative non-profit Research and Development (R&D) model and is the first new chemical entity to be developed by DNDi. This therapeutic breakthrough is testament to the unique partnership between DNDi and Sanofi to discover, develop, and register a treatment for a severely neglected disease,” said Dr Bernard Pécoul, DNDi executive director. “

The approval paves way for the distribution of fexinidazole in 2019. It is the result clinical trials and a 10-year partnership between the non-profit research and development organization Drugs for Neglected Diseases initiative (DNDi), the pharmaceutical giant Sanofi and African partners.

Sleeping sickness, or human African trypanosomiasis (HAT), is usually fatal without treatment. It is transmitted by the bite of tsetse fly and places nearly 65 million people in sub-Sahara Africa are at risk. To develop fexinidazole, DNDspent EUR 55 million (USD 62.5 million), which includes costs related to pre-clinical development and clinical studies.

I’ve dedicated my life as a doctor to sleeping sickness. An all-oral treatment has been a dream of mine for decades. Those affected are some of the most vulnerable and live in some of the most remote areas of the Congo, if not the world. They need a treatment that is safe, effective and simple,” said Dr Victor Kande, one of the world’s leading experts dealing with Neglected Tropical Diseases advising the Ministry of Health of the Democratic Republic of Congo (DRC).

According to Dr Kande who was the principal investigator of the trials, “less than ten years ago we were still treating this disease with an arsenic derivative that killed 5% of all patients, fexinidazole comes as a simple pill making it a huge leap in how we can tackle this deadly disease.”

In the complex world of medicine fexinidazole is among organic compounds (5-nitroimidazole derivative) used as antibiotics against infections caused by anaerobic bacteria and various parasitic infections. It was rediscovered in 2005 through collaboration with the Swiss Tropical and Public Health Institute, when DNDi’s was searching for compounds with anti-parasitic activity, after being developed and then abandoned for strategic reasons by Hoechst (now Sanofi) in the 1980s.

In 2009, DNDi and Sanofi concluded a collaboration agreement for the development, manufacturing, and distribution of fexinidazole, with DNDi responsible for pre-clinical, clinical, and pharmaceutical development, and Sanofi for industrial development, registration, production, and distribution of the drug.

This therapeutic breakthrough is the latest milestone in Sanofi’s long-term commitment to sleeping sickness,” said Dr Ameet Nathwani, chief medical officer and executive Vice President Medical Function. Fexinidazole is the proof that partnerships between public and private sectors can deliver safe and effective medicines for the most neglected patients. Sanofi is proud to donate this medicine to the World Health Organization as part of our mission to support the elimination of sleeping sickness.”

In December 2017, Sanofi submitted a regulatory dossier to the European Medicines Agency under Article 58 of Regulation 726/2004, an innovative regulatory mechanism intended for the review of new medicines destined for use outside of the European Union.

By allowing for the participation of endemic countries (DRC and Uganda) and of the WHO in the evaluation of the fexinidazole regulatory dossier, approval under Article 58 also facilitates and could accelerate future national product registrations and patient access.

Together with Ministries of Health in endemic countries we have shown it is possible to conduct high quality trials in the most challenging settings,” said Dr Nathalie Strub-Wourgaft, DNDi Director of Neglected Tropical Diseases. “This is only the first step – we now need to ensure patients can access and benefit from this new drug.”

The project was supported by seven European countries (France, Germany, the Netherlands, Norway, Spain, Switzerland, and the UK) as well as private donors including the Bill & Melinda Gates Foundation and Médecins Sans Frontières.

The latest data released by the WHO in July 2018 confirm a sustained decrease in the number of new cases. Only 1,447 new cases were reported to the WHO in 2017 compared to 2,164 cases in 2016 and 9,870 cases in 2009. However the history of sleeping sickness is marked by resurgence, interspersed by decades where the disease has seemed largely under control.

DNDi works to deliver new treatments for neglected diseases, in particular Human African Trypanosomiasis (HAT), leishmaniasis, Chagas disease, filarial infections, mycetoma, paediatric HIV, and hepatitis C. Fexinidazole is the first new chemical entity to be successfully developed by DNDi. (Contacts: imoss@dndi.org, mgibbons@dndi.orgmr@sanofi.com, ir@sanofi.com)

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