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Fexinidazole

April 12, 2024

Fexinidazole is a medication used to treat African trypanosomiasis (sleeping sickness) caused by Trypanosoma brucei gambiense.[3] It is effective against both first and second stage disease.[3] Also a potential new treatment for Chagas disease, a neglected tropical disease that affects millions of people worldwide.[4] It is taken by mouth.[5]

Fexinidazole
Clinical data
Other names
  • Fexinidazole Winthrop
  • HOE 239
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Identifiers
  • 1-Methyl-2-{[4-(methylsulfanyl)phenoxy]methyl}-5-nitro-1H-imidazole
CAS Number
  • 59729-37-2
PubChem CID
  • 68792
DrugBank
  • DB12265
ChemSpider
  • 62032
UNII
  • 306ERL82IR
KEGG
  • D11252
ChEMBL
  • ChEMBL1631694
CompTox Dashboard (EPA)
  • DTXSID00208448
ECHA InfoCard100.207.619
Chemical and physical data
FormulaC12H13N3O3S
Molar mass279.31 g·mol−1
3D model (JSmol)
  • Interactive image
  • [O-] [N+](=O)c1cnc(n1C)COc2ccc(SC)cc2
  • InChI=1S/C12H13N3O3S/c1-14-11(13-7-12(14)15(16)17)8-18-9-3-5-10(19-2)6-4-9/h3-7H,8H2,1-2H3
  • Key:MIWWSGDADVMLTG-UHFFFAOYSA-N

Common side effects include nausea, vomiting, headache, and trouble sleeping.[6] Other side effects may include QT prolongation, psychosis, and low white blood cells.[7] It is unclear if use during pregnancy or breast feeding is safe.[7] Fexinidazole is in the antiparasitic and the nitroimidazole family of medications.[5] It is believed to work by turning on certain enzymes within the parasites that result in their death.[6]

Fexinidazole was first described in 1978.[8] It was given a positive opinion by the European Medicines Agency in 2018.[6] It is on the World Health Organization's List of Essential Medicines.[9][10] Development for sleeping sickness was funded by the Drugs for Neglected Diseases initiative in collaboration with Sanofi.[11] Fexinidazole was approved for medical use in the United States in July 2021.[1]

Medical use edit

Sleeping sickness edit

A trial in Africa found fexinidazole to be 91% effective at treating sleeping sickness.[6][12] Though less effective than nifurtimox with eflornithine in severe disease, fexinidazole has the benefit that it can be taken by mouth.[6]

Fexinidazole is the first drug candidate for the treatment of advanced-stage sleeping sickness in thirty years.[13]

Efficacy and safety edit

In cell culture, fexinidazole has an IC50 of around 1–4μM against Trypanosoma brucei.[14] In the mouse model, fexinidazole cures both the first, haemolymphatic, and the second, meningoencephalitic stage of the infection, the latter at 100 mg/kg twice daily for 5 days. In patients, the clinical trials managed by DNDi and supported by Swiss TPH mainly conducted in the Democratic Republic of the Congo demonstrated that oral fexinidazole is safe and effective for use against first- and early second-stage sleeping sickness. Based on the positive opinion issued by the European Medicines Agency in 2018, the WHO has released new interim guidelines for the treatment of HAT including fexinidazole as the new therapy for first-stage and non-severe second-stage sleeping sickness caused by Trypanosoma brucei gambiense (gHAT) [15] Recently, a study of the safety and efficacy of oral fexinidazole in children with gambiense human African trypanosomiasis was accomplished and concluded that orally administered fexinidazole showed high efficacy across all stages of gambiense human African trypanosomiasis infection in children aged 6 years and older and weighing more than 20 kg. The benefit-to-risk ratio of fexinidazole for treating children with gambiense human African trypanosomiasis, regardless of disease stage, is positive. Current interventions for diagnosing, staging, and treating gambiense human African trypanosomiasis require resources, trained personnel, equipment, and hospital infrastructure. These potentially costly procedures are therefore difficult to implement in remote areas or in those that might be mired in conflict, which could prevent the goal of eliminating gambiense human African trypanosomiasis by 2030.25,26 Simplified oral treatments such as fexinidazole or single-dose oral treatments such as acoziborole (currently in clinical trials)27 that can cure both disease stages of gambiense human African trypanosomiasis and circumvent the need for systematic disease staging with lumbar puncture (a procedure associated with complications and anxiety, particularly in children28) would benefit both patients and health-care professionals [16] Furthermore, Damasio et al. evaluated the in vivo oral efficacy of self-emulsifying drug delivery systems (SEDDS) containing fexinidazole (FEX) in the experimental treatment of visceral leishmaniasis (VL). The developed FEX-SEDDS formulation presented as a clear, yellowish liquid without precipitate. In the simulated gastric and intestinal media, the FEX-SEDDS had a size of 97 ± 1 and 106 ± 9 nm, respectively. The FEX retention in droplets after SEDDS dilution in simulated gastrointestinal media was almost 100%. Antileishmanial efficacy studies showed that FEX-SEDDS was the only treatment able to significantly (p < 0.05) reduce the parasite burden in the liver and spleen of animals experimentally infected with Leishmania infantum [17]

Mechanism of action edit

The biologically relevant active metabolites in vivo are the sulfoxide and sulfone.[18][19]

Synthesis edit

 
Synthetic pathway of fexinidzaole, adapted from Scheme 3 of McInturff et al. 2023.[20]

History edit

Fexinidazole was discovered by the German pharmaceutical company Hoechst AG, but its development as a pharmaceutical was halted in the 1980s.[21]

The US Food and Drug Administration granted the application for fexinidazole orphan drug designation.[22]

Society and culture edit

Fexinidazole Winthrop, a Sanofi-Aventis product developed with the Drugs for Neglected Diseases Initiative (DNDi), received a positive endorsement from the European Medicines Agency in 2018, for use in non-European markets.[23][24] It was approved for the treatment of Trypanosoma brucei gambiense human African trypanosomiasis (HAT) in the Democratic Republic of the Congo (DRC) in December 2018.[25] Fexinidazole was included in the 'role of honour' in Préscrire magazine's 2020 prize list.Fexinidazole Winthrop° (fexinidazole) : au Tableau d'Honneur 2020

Veterinary use edit

Fexinidazole is promising in African animal trypanosomiasis. Torreele et al. 2010 found the drug to be effective against T. b. gambiense infection of mice, rats, rabbits and beagles. They also found no toxicity in any of them, including a lack of mutagenicity despite in vitro mutagenicity.[26]

References edit

  1. ^ a b "Fexinidazole: FDA-Approved Drugs". U.S. Food and Drug Administration. Retrieved 16 July 2021.
  2. ^ "Fexinidazole tablet". DailyMed. U.S. National Library of Medicine. Retrieved 20 August 2021.
  3. ^ a b . European Medicines Agency. 22 January 2019. Archived from the original on 18 January 2021. Retrieved 12 November 2019.
  4. ^ Torrico F, Gascón J, Ortiz L, Pinto J, Rojas G, Palacios A, et al. (February 2023). "A Phase 2, Randomized, Multicenter, Placebo-Controlled, Proof-of-Concept Trial of Oral Fexinidazole in Adults With Chronic Indeterminate Chagas Disease". Clinical Infectious Diseases. 76 (3): e1186–e1194. doi:10.1093/cid/ciac579. PMC 9907522. PMID 35925555.
  5. ^ a b Deeks ED (February 2019). "Fexinidazole: First Global Approval". Drugs. 79 (2): 215–220. doi:10.1007/s40265-019-1051-6. PMID 30635838. S2CID 57772417.
  6. ^ a b c d e (PDF). EMA. Archived from the original (PDF) on 2 January 2021. Retrieved 12 November 2019.
  7. ^ a b (PDF). EMA. Archived from the original (PDF) on 12 November 2019. Retrieved 12 November 2019.
  8. ^ Mowbray CE (2017). "Antileishmanial Drug Discovery: Past, Present, and Future Perspectives". In Gil C, Rivas L (eds.). Drug Discovery for Leishmaniasis. Royal Society of Chemistry. p. 30. ISBN 9781788012584.
  9. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  10. ^ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  11. ^ "Fexinidazole – DNDi". www.dndi.org. 31 December 2004. Retrieved 12 November 2019.
  12. ^ Mesu VK, Kalonji WM, Bardonneau C, Mordt OV, Blesson S, Simon F, et al. (January 2018). "Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial". Lancet. 391 (10116): 144–154. doi:10.1016/s0140-6736(17)32758-7. PMID 29113731. S2CID 46781585.
  13. ^ Torreele E, Bourdin Trunz B, Tweats D, Kaiser M, Brun R, Mazué G, et al. (December 2010). Boelaert M (ed.). "Fexinidazole--a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness". PLOS Neglected Tropical Diseases. 4 (12): e923. doi:10.1371/journal.pntd.0000923. PMC 3006138. PMID 21200426.
  14. ^ Kaiser M, Bray MA, Cal M, Bourdin Trunz B, Torreele E, Brun R (December 2011). "Antitrypanosomal activity of fexinidazole, a new oral nitroimidazole drug candidate for treatment of sleeping sickness". Antimicrobial Agents and Chemotherapy. 55 (12). American Society for Microbiology: 5602–5608. doi:10.1128/aac.00246-11. PMC 3232772. PMID 21911566.
  15. ^ Bernhard S, Kaiser M, Burri C, Mäser P (October 2022). "Fexinidazole for Human African Trypanosomiasis, the Fruit of a Successful Public-Private Partnership". Diseases. 10 (4): 90. doi:10.3390/diseases10040090. PMC 9589988. PMID 36278589.
  16. ^ Kande Betu Kumesu V, Mutombo Kalonji W, Bardonneau C, Valverde Mordt O, Ngolo Tete D, Blesson S, et al. (November 2022). "Safety and efficacy of oral fexinidazole in children with gambiense human African trypanosomiasis: a multicentre, single-arm, open-label, phase 2-3 trial". The Lancet. Global Health. 10 (11): e1665–e1674. doi:10.1016/S2214-109X(22)00338-2. PMC 9554014. PMID 36179736.
  17. ^ Damasio DS, Antunes PA, Lages EB, Morais-Teixeira E, Vital KD, Cardoso VN, et al. (January 2023). "A new oral self-emulsifying drug delivery system improves the antileishmania efficacy of fexinidazole in vivo". International Journal of Pharmaceutics. 631: 122505. doi:10.1016/j.ijpharm.2022.122505. PMID 36549405. S2CID 254917177.
  18. ^ Wyllie S, Patterson S, Stojanovski L, Simeons FR, Norval S, Kime R, et al. (February 2012). "The anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis". Science Translational Medicine. 4 (119): 119re1. doi:10.1126/scitranslmed.3003326. PMC 3457684. PMID 22301556.
  19. ^ Sokolova AY, Wyllie S, Patterson S, Oza SL, Read KD, Fairlamb AH (July 2010). "Cross-resistance to nitro drugs and implications for treatment of human African trypanosomiasis". Antimicrobial Agents and Chemotherapy. 54 (7): 2893–2900. doi:10.1128/AAC.00332-10. PMC 2897277. PMID 20439607.
  20. ^ McInturff EL, France SP, Leverett CA, Flick AC, Lindsey EA, Berritt S, et al. (August 2023). "Synthetic Approaches to the New Drugs Approved During 2021". Journal of Medicinal Chemistry. 66 (15). American Chemical Society (ACS): 10150–10201. doi:10.1021/acs.jmedchem.3c00501. PMID 37528515. S2CID 260377572.
  21. ^ McNeil Jr D (8 January 2008). "Jump-Start on Slow Trek to Treatment for a Disease". The New York Times.
  22. ^ Advancing Health Through Innovation: New Drug Therapy Approvals 2021 (PDF). U.S. Food and Drug Administration (FDA) (Report). 13 May 2022. from the original on 6 December 2022. Retrieved 22 January 2023.   This article incorporates text from this source, which is in the public domain.
  23. ^ "CHMP Summary of Opinion - Fexinidazole Winthrop" (PDF). Retrieved 19 November 2018.
  24. ^ McNeil Jr D (16 November 2018). "Rapid Cure Approved for Sleeping Sickness, a Horrific Illness". The New York Times. Retrieved 20 November 2018.
  25. ^ "Fexinidazole, the first all-oral treatment for sleeping sickness, approved in Democratic Republic of Congo". Drugs for Neglected Diseases Initiative (DNDi). 29 January 2019. Retrieved 4 June 2019.
  26. ^ Kennedy PG (February 2013). "Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness)". The Lancet. Neurology. 12 (2). Elsevier: 186–194. doi:10.1016/s1474-4422(12)70296-x. PMID 23260189. S2CID 8688394.

External links edit

  • "Fexinidazole". Drug Information Portal. U.S. National Library of Medicine.

April 12, 2024
fexinidazole, medication, used, treat, african, trypanosomiasis, sleeping, sickness, caused, trypanosoma, brucei, gambiense, effective, against, both, first, second, stage, disease, also, potential, treatment, chagas, disease, neglected, tropical, disease, tha. Fexinidazole is a medication used to treat African trypanosomiasis sleeping sickness caused by Trypanosoma brucei gambiense 3 It is effective against both first and second stage disease 3 Also a potential new treatment for Chagas disease a neglected tropical disease that affects millions of people worldwide 4 It is taken by mouth 5 FexinidazoleClinical dataOther namesFexinidazole WinthropHOE 239License dataUS DailyMed FexinidazoleRoutes ofadministrationBy mouthATC codeP01CA03 WHO Legal statusLegal statusUS only 1 2 IdentifiersIUPAC name 1 Methyl 2 4 methylsulfanyl phenoxy wbr methyl 5 nitro 1H imidazoleCAS Number59729 37 2PubChem CID68792DrugBankDB12265ChemSpider62032UNII306ERL82IRKEGGD11252ChEMBLChEMBL1631694CompTox Dashboard EPA DTXSID00208448ECHA InfoCard100 207 619Chemical and physical dataFormulaC 12H 13N 3O 3SMolar mass279 31 g mol 13D model JSmol Interactive imageSMILES O N O c1cnc n1C COc2ccc SC cc2InChI InChI 1S C12H13N3O3S c1 14 11 13 7 12 14 15 16 17 8 18 9 3 5 10 19 2 6 4 9 h3 7H 8H2 1 2H3Key MIWWSGDADVMLTG UHFFFAOYSA NCommon side effects include nausea vomiting headache and trouble sleeping 6 Other side effects may include QT prolongation psychosis and low white blood cells 7 It is unclear if use during pregnancy or breast feeding is safe 7 Fexinidazole is in the antiparasitic and the nitroimidazole family of medications 5 It is believed to work by turning on certain enzymes within the parasites that result in their death 6 Fexinidazole was first described in 1978 8 It was given a positive opinion by the European Medicines Agency in 2018 6 It is on the World Health Organization s List of Essential Medicines 9 10 Development for sleeping sickness was funded by the Drugs for Neglected Diseases initiative in collaboration with Sanofi 11 Fexinidazole was approved for medical use in the United States in July 2021 1 Contents 1 Medical use 1 1 Sleeping sickness 1 2 Efficacy and safety 2 Mechanism of action 3 Synthesis 4 History 5 Society and culture 6 Veterinary use 7 References 8 External linksMedical use editSleeping sickness edit A trial in Africa found fexinidazole to be 91 effective at treating sleeping sickness 6 12 Though less effective than nifurtimox with eflornithine in severe disease fexinidazole has the benefit that it can be taken by mouth 6 Fexinidazole is the first drug candidate for the treatment of advanced stage sleeping sickness in thirty years 13 Efficacy and safety edit In cell culture fexinidazole has an IC50 of around 1 4mM against Trypanosoma brucei 14 In the mouse model fexinidazole cures both the first haemolymphatic and the second meningoencephalitic stage of the infection the latter at 100 mg kg twice daily for 5 days In patients the clinical trials managed by DNDi and supported by Swiss TPH mainly conducted in the Democratic Republic of the Congo demonstrated that oral fexinidazole is safe and effective for use against first and early second stage sleeping sickness Based on the positive opinion issued by the European Medicines Agency in 2018 the WHO has released new interim guidelines for the treatment of HAT including fexinidazole as the new therapy for first stage and non severe second stage sleeping sickness caused by Trypanosoma brucei gambiense gHAT 15 Recently a study of the safety and efficacy of oral fexinidazole in children with gambiense human African trypanosomiasis was accomplished and concluded that orally administered fexinidazole showed high efficacy across all stages of gambiense human African trypanosomiasis infection in children aged 6 years and older and weighing more than 20 kg The benefit to risk ratio of fexinidazole for treating children with gambiense human African trypanosomiasis regardless of disease stage is positive Current interventions for diagnosing staging and treating gambiense human African trypanosomiasis require resources trained personnel equipment and hospital infrastructure These potentially costly procedures are therefore difficult to implement in remote areas or in those that might be mired in conflict which could prevent the goal of eliminating gambiense human African trypanosomiasis by 2030 25 26 Simplified oral treatments such as fexinidazole or single dose oral treatments such as acoziborole currently in clinical trials 27 that can cure both disease stages of gambiense human African trypanosomiasis and circumvent the need for systematic disease staging with lumbar puncture a procedure associated with complications and anxiety particularly in children28 would benefit both patients and health care professionals 16 Furthermore Damasio et al evaluated the in vivo oral efficacy of self emulsifying drug delivery systems SEDDS containing fexinidazole FEX in the experimental treatment of visceral leishmaniasis VL The developed FEX SEDDS formulation presented as a clear yellowish liquid without precipitate In the simulated gastric and intestinal media the FEX SEDDS had a size of 97 1 and 106 9 nm respectively The FEX retention in droplets after SEDDS dilution in simulated gastrointestinal media was almost 100 Antileishmanial efficacy studies showed that FEX SEDDS was the only treatment able to significantly p lt 0 05 reduce the parasite burden in the liver and spleen of animals experimentally infected with Leishmania infantum 17 Mechanism of action editThe biologically relevant active metabolites in vivo are the sulfoxide and sulfone 18 19 Synthesis edit nbsp Synthetic pathway of fexinidzaole adapted from Scheme 3 of McInturff et al 2023 20 History editFexinidazole was discovered by the German pharmaceutical company Hoechst AG but its development as a pharmaceutical was halted in the 1980s 21 The US Food and Drug Administration granted the application for fexinidazole orphan drug designation 22 Society and culture editFexinidazole Winthrop a Sanofi Aventis product developed with the Drugs for Neglected Diseases Initiative DNDi received a positive endorsement from the European Medicines Agency in 2018 for use in non European markets 23 24 It was approved for the treatment of Trypanosoma brucei gambiense human African trypanosomiasis HAT in the Democratic Republic of the Congo DRC in December 2018 25 Fexinidazole was included in the role of honour in Prescrire magazine s 2020 prize list Fexinidazole Winthrop fexinidazole au Tableau d Honneur 2020Veterinary use editFexinidazole is promising in African animal trypanosomiasis Torreele et al 2010 found the drug to be effective against T b gambiense infection of mice rats rabbits and beagles They also found no toxicity in any of them including a lack of mutagenicity despite in vitro mutagenicity 26 References edit a b Fexinidazole FDA Approved Drugs U S Food and Drug Administration Retrieved 16 July 2021 Fexinidazole tablet DailyMed U S National Library of Medicine Retrieved 20 August 2021 a b Fexinidazole Winthrop H W 2320 European Medicines Agency 22 January 2019 Archived from the original on 18 January 2021 Retrieved 12 November 2019 Torrico F Gascon J Ortiz L Pinto J Rojas G Palacios A et al February 2023 A Phase 2 Randomized Multicenter Placebo Controlled Proof of Concept Trial of Oral Fexinidazole in Adults With Chronic Indeterminate Chagas Disease Clinical Infectious Diseases 76 3 e1186 e1194 doi 10 1093 cid ciac579 PMC 9907522 PMID 35925555 a b Deeks ED February 2019 Fexinidazole First Global Approval Drugs 79 2 215 220 doi 10 1007 s40265 019 1051 6 PMID 30635838 S2CID 57772417 a b c d e Fexinidazole Winthrop fexinidazole PDF EMA Archived from the original PDF on 2 January 2021 Retrieved 12 November 2019 a b Fexinidazole Winthrop PDF EMA Archived from the original PDF on 12 November 2019 Retrieved 12 November 2019 Mowbray CE 2017 Antileishmanial Drug Discovery Past Present and Future Perspectives In Gil C Rivas L eds Drug Discovery for Leishmaniasis Royal Society of Chemistry p 30 ISBN 9781788012584 World Health Organization 2019 World Health Organization model list of essential medicines 21st list 2019 Geneva World Health Organization hdl 10665 325771 WHO MVP EMP IAU 2019 06 License CC BY NC SA 3 0 IGO World Health Organization 2021 World Health Organization model list of essential medicines 22nd list 2021 Geneva World Health Organization hdl 10665 345533 WHO MHP HPS EML 2021 02 Fexinidazole DNDi www dndi org 31 December 2004 Retrieved 12 November 2019 Mesu VK Kalonji WM Bardonneau C Mordt OV Blesson S Simon F et al January 2018 Oral fexinidazole for late stage African Trypanosoma brucei gambiense trypanosomiasis a pivotal multicentre randomised non inferiority trial Lancet 391 10116 144 154 doi 10 1016 s0140 6736 17 32758 7 PMID 29113731 S2CID 46781585 Torreele E Bourdin Trunz B Tweats D Kaiser M Brun R Mazue G et al December 2010 Boelaert M ed Fexinidazole a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness PLOS Neglected Tropical Diseases 4 12 e923 doi 10 1371 journal pntd 0000923 PMC 3006138 PMID 21200426 Kaiser M Bray MA Cal M Bourdin Trunz B Torreele E Brun R December 2011 Antitrypanosomal activity of fexinidazole a new oral nitroimidazole drug candidate for treatment of sleeping sickness Antimicrobial Agents and Chemotherapy 55 12 American Society for Microbiology 5602 5608 doi 10 1128 aac 00246 11 PMC 3232772 PMID 21911566 Bernhard S Kaiser M Burri C Maser P October 2022 Fexinidazole for Human African Trypanosomiasis the Fruit of a Successful Public Private Partnership Diseases 10 4 90 doi 10 3390 diseases10040090 PMC 9589988 PMID 36278589 Kande Betu Kumesu V Mutombo Kalonji W Bardonneau C Valverde Mordt O Ngolo Tete D Blesson S et al November 2022 Safety and efficacy of oral fexinidazole in children with gambiense human African trypanosomiasis a multicentre single arm open label phase 2 3 trial The Lancet Global Health 10 11 e1665 e1674 doi 10 1016 S2214 109X 22 00338 2 PMC 9554014 PMID 36179736 Damasio DS Antunes PA Lages EB Morais Teixeira E Vital KD Cardoso VN et al January 2023 A new oral self emulsifying drug delivery system improves the antileishmania efficacy of fexinidazole in vivo International Journal of Pharmaceutics 631 122505 doi 10 1016 j ijpharm 2022 122505 PMID 36549405 S2CID 254917177 Wyllie S Patterson S Stojanovski L Simeons FR Norval S Kime R et al February 2012 The anti trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis Science Translational Medicine 4 119 119re1 doi 10 1126 scitranslmed 3003326 PMC 3457684 PMID 22301556 Sokolova AY Wyllie S Patterson S Oza SL Read KD Fairlamb AH July 2010 Cross resistance to nitro drugs and implications for treatment of human African trypanosomiasis Antimicrobial Agents and Chemotherapy 54 7 2893 2900 doi 10 1128 AAC 00332 10 PMC 2897277 PMID 20439607 McInturff EL France SP Leverett CA Flick AC Lindsey EA Berritt S et al August 2023 Synthetic Approaches to the New Drugs Approved During 2021 Journal of Medicinal Chemistry 66 15 American Chemical Society ACS 10150 10201 doi 10 1021 acs jmedchem 3c00501 PMID 37528515 S2CID 260377572 McNeil Jr D 8 January 2008 Jump Start on Slow Trek to Treatment for a Disease The New York Times Advancing Health Through Innovation New Drug Therapy Approvals 2021 PDF U S Food and Drug Administration FDA Report 13 May 2022 Archived from the original on 6 December 2022 Retrieved 22 January 2023 nbsp This article incorporates text from this source which is in the public domain CHMP Summary of Opinion Fexinidazole Winthrop PDF Retrieved 19 November 2018 McNeil Jr D 16 November 2018 Rapid Cure Approved for Sleeping Sickness a Horrific Illness The New York Times Retrieved 20 November 2018 Fexinidazole the first all oral treatment for sleeping sickness approved in Democratic Republic of Congo Drugs for Neglected Diseases Initiative DNDi 29 January 2019 Retrieved 4 June 2019 Kennedy PG February 2013 Clinical features diagnosis and treatment of human African trypanosomiasis sleeping sickness The Lancet Neurology 12 2 Elsevier 186 194 doi 10 1016 s1474 4422 12 70296 x PMID 23260189 S2CID 8688394 External links edit Fexinidazole Drug Information Portal U S National Library of Medicine Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Fexinidazole amp oldid 1218254430, wikipedia, wiki, book, books, library,

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