Develop and register fexinidazole as a new all oral treatment for the treatment of stage-1 and stage-2 sleeping sickness caused by T.b. gambiense (g-HAT), in adults and children above the age of six and above 20kg.
current phase of drug development
updated 29 Feb 2020
First new chemical entity developed by DNDi and the first all-oral cure for all stages of sleeping sickness
Easy-to-use medicine brings treatment closer to patients
NECT, a combination of nifurtimox and eflornithine, was approved for sleeping sickness in 2009, replacing very toxic or complicated drugs. But treatment remained cumbersome, difficult to ship, store, and administer; patients needed to be hospitalized to receive the intravenous infusions and undergo a lumbar puncture to determine the stage of the disease since NECT is only indicated for stage-2.
DNDi, in collaboration with the Swiss Tropical and Public Health, rediscovered the 5-nitroimidazole derivative fexinidazole during a search for compounds with anti-parasitic activity in 2005. The compound had been developed but abandoned for strategic reasons by Hoechst (now Sanofi) in the 1980s. In 2009, DNDi and Sanofi concluded a collaboration agreement.
More than two million people were screened for sleeping sickness as part of three fexinidazole clinical trials, which enrolled 749 patients in the Democratic Republic of Congo and Central African Republic and had to overcome unique challenges of conducting trials in remote areas where sleeping sickness occurs. In the trials, fexinidazole showed high efficacy and safety in both stages of the disease, both in adults and children.
Fexinidazole is the first all-oral treatment for both stages of T. b. gambiense sleeping sickness, the most common form of the disease. Taken as simple pills for 10 days, fexinidazole presents significant advantages over NECT because it eliminates the need for systematic hospitalization and potentially leads to a reduction in the number of lumbar punctures. The European Medicines Agency adopted a positive scientific opinion of fexinidazole in late 2018, paving the way for registration and distribution in endemic countries.
Fexinidazole is the first new chemical entity to have been developed by DNDi, which has steered its progression through all stages of the drug development pipeline from lab to patient.
- Indication: stage-1 and stage-2 gambiense sleeping sickness (human African trypanosomiasis)
- Dosage: Adults: 3 tablets once-a-day for 4 days, and 2 tablets once-a-day for next 6 daysChildren (≥ 6 years old & ≥ 20 kg): 2 tablets once-a-day for 4 days, and 1 tablet once-a-day for next 6 days
- Recommended in November 2018 by the European Medicines Agency under Article 58, an innovative regulatory mechanism for the review of new medicines destined for use outside of the European Union
- Approved in the Democratic Republic of Congo in 2019
- Registration submission in other endemic countries underway
- Sanofi has committed to donate fexinidazole to WHO, which will distribute it to National Control Programmes in endemic countries
- Developed in partnership between DNDi, Sanofi, the HAT Platform, national control programmes of the Democratic Republic of the Congo and Central African Republic, Médecins Sans Frontières, Swiss Tropical & Public Health Institute, with support of the World Health Organization, Department of Control of Neglected Tropical Diseases
‘Those affected by sleeping sickness 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. An all-oral treatment has been a dream of mine for decades. Fexinidazole is a huge leap in how we can tackle this deadly disease.’
Dr Victor Kande, NTD Expert Advisor to the Ministry of Health of DRC and principal investigator of the fexinidazole clinical trials
Key scientific articles
Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial. The Lancet, November 2017
by Kande Betu Ku Mesu V, Mutombo Kalonji W, Bardonneau C, Valverde Mordt O, Blesson S, Simon F, Delhomme S, Bernhard S, Kuziena W, Fina Lubaki JP, Lumeya Vuvu S, Nganzobo Ngima P, Mahenzi Mbembo H, Ilunga M, Kasongo Bonama A, Amici Heradi J, Lumaliza Solomo JL, Mandula G, Kaninda Badibabi L, Regongbenga Dama F, Kavunga Lukula P, Ngolo Tete D, Lumbala C, Scherrer B, Strub-Wourgaft N, Tarral A.
Determination of an optimal dosing regimen for fexinidazole, a novel oral drug for the treatment of human African trypanosomiasis: First-in-human studies. Clinical Pharmacokinetics, February 2014
by Tarral A, Blesson S, Valverde Mordt O, Torreele E, Sassella D, Bray MA, Hovsepian L, Evène E, Gualano V, Felices M, Strub-Wourgaft N.
Genotoxicity profile of fexinidazole – a drug candidate in clinical development for human African trypanomiasis (sleeping sickness). Mutagenesis, September 2012
by Tweats D, Bourdin Trunz B, Torreele E.
Antitrypanosomal activity of fexinidazole, a new oral nitroimidazole drug candidate for treatment of sleeping sickness. Antimicrob Agents Chemother, December 2011
by Kaiser M, Bray MA, Cal M, Bourdin Trunz B, Torreele E, and Brun R.
Fexinidazole – A new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness. PLOS Neglected Tropical Diseases, December 2010
by Torreele E, Bourdin Trunz B, Tweats D, Kaiser M, Brun R, Mazué G, Bray M A, Pécoul B.
News and press releases
- 1 February 2021 – Fexinidazole awarded in the prestigious ‘2020 medicines list’ of the independant journal Prescrire
- 10 July 2019 – WHO adds first all-oral sleeping sickness drug to Essential Medicines List
- 30 January 2019 – Fexinidazole, the first all-oral treatment for sleeping sickness, approved in Democratic Republic of Congo
- 16 November 2018 – European Medicines Agency recommends fexinidazole, the first all-oral treatment for sleeping sickness
- 31 January 2018 – Sanofi, DNDi seek European Medicines Agency review for sleeping sickness treatment
- 4 November 2017 – Phase II/III studies show high efficacy and safety of fexinidazole, the first oral treatment for sleeping sickness
- 6 December 2012 – New oral drug candidate for African sleeping sickness
- Clinical study protocol: DNDiFEX004
- Clinical study protocol: DNDiHATFEX005
- Clinical study protocol: DNDiHATFEX006
*From 2005 to 2018, DNDi invested EUR 55 million for the full development of fexinidazole from discovery to clinical trials development (except the Phase IIIb trial that started in 2016 to obtain more information about special populations not included in previous fexinidazole trials). Project cost includes direct and indirect costs, but it does not include in-kind contributions. As of December 2018, Sanofi estimates an overall contribution of EUR 13 million (including regulatory, human resources, industrial activities, etc.).
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