Develop and register fexinidazole as a new all-oral treatment for Stage 1 and Stage 2 sleeping sickness caused by T.b. gambiense in adults and children above the age of six and over 20 kg
current phase of drug development
updated 19 Jul 2021
First new chemical entity developed by DNDi and the first all-oral cure for both stages of T.b. gambiense sleeping sickness
Easy-to-use medicine brings treatment closer to patients
Fexinidazole is the first all-oral treatment for both stages of T.b. gambiense sleeping sickness, the most common form of the disease. Fexinidazole is an oral pill taken for 10 days, offering significant advantages over the previous standard of care, NECT, because it eliminates the need for systematic hospitalization and leads to a reduction in the number of lumbar punctures. The European Medicines Agency adopted a positive scientific opinion on fexinidazole in late 2018, paving the way for registration and distribution in endemic countries. The drug was registered in the Democratic Republic of Congo in December 2018.
Fexinidazole is the first new chemical entity developed by DNDi, which has steered its progression through all stages of the drug development pipeline from lab to patient. The search began in 2005, when DNDi. in collaboration with the Swiss Tropical and Public Health Institute, undertook an extensive compound mining exercise to search for anti-parasitic activity and rediscovered fexinidazole, whose development had been shelved by Hoechst AG (now Sanofi) in the 1980s. After completing preclinical studies, DNDi partnered with Sanofi from 2009 onwards for the development, manufacturing, and distribution of fexinidazole. Phase I studies started in 2009, and a Phase II/III clinical trial began in the Democratic Republic of Congo and the Central African Republic in 2012.
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 for adults and children.
In June 2019, fexinidazole was added to the World Health Organization (WHO) Essential Medicines List for children and adults. In August 2019, WHO published new sleeping sickness treatment guidelines to include fexinidazole as the first-line treatment for T.b. gambiense, except in cases of advanced disease. In 2020, DNDi and Sanofi also started the process to register fexinidazole with the US Federal Drug Administration.
Fexinidazole is now being donated by Sanofi to WHO for distribution to national sleeping sickness control programmes in disease-endemic countries. Distribution in the Democratic Republic of Congo began in January 2020.
DNDi is now striving to make fexinidazole available to the majority of people who have T.b. gambiense sleeping sickness. We are supporting a three-year access and pharmacovigilance study that began in 2020 and have so far carried out in-country training of relevant staff in 250 hospitals and health centres in T.b. gambiense-endemic countries; and updated national treatment and pharmacovigilance guidelines in Angola, Central African Republic, the Democratic Republic of Congo, Equatorial Guinea, Guinea, and Chad.
DNDi has successfully completed a Phase IIIb trial to obtain clinical data on special populations not included in previous trials, including pregnant and breast-feeding women, and people with poor nutritional status or chronic diseases. The final report is being prepared.
- Indication: Stage 1 and Stage 2 T.b. gambiense sleeping sickness (human African trypanosomiasis)
- Dosage: Adults: 3 tablets once-a-day for 4 days, and 2 tablets once-a-day for the next 6 days; Children (≥ 6 years old & ≥ 20 kg): 2 tablets once-a-day for 4 days, and 1 tablet once-a-day for the 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
- Registered in the Democratic Republic of Congo in 2018
- Approved by the US Food and Drug Administration (FDA) in July 2021.
- 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, Central African Republic, and Guinea, Médecins Sans Frontières, Swiss Tropical and Public Health Institute, with support from the World Health Organization’s 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 stage 1 or early stage 2 African Trypanosoma brucei gambiense trypanosomiasis: A prospective, multicentre, open-label, cohort study. The Lancet Global Health, June 2021.
by Kande Betu Ku Mesu V, Mutombo Kalonji W, Bardonneau C, Valverde Mordt O, Ngolo Tete D, Blesson S, Simon F, Delhomme S, Bernhard S, Mahenzi Mbembo H, Mpia Moke C, Lumeya Vuvu S, Mudji E’kitiak J, Akwaso Masa F, Mukendi Ilunga M, Mpoyi Muamba Nzambi D, Mayala Malu T, Kapongo Tshilumbwa S, Botalema Bolengi F, Nkieri Matsho M, Lumbala C, Scherrer B, Strub-Wourgaft N, Tarral A.
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
- 19 July 2021 – US FDA approves fexinidazole as the first all-oral treatment for sleeping sickness
- 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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