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Tafenoquine: First Global Approval

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Abstract

Tafenoquine (Krintafel™, Arakoda™), an orally-active 8-aminoquinoline anti-malarial drug, is a long-acting analogue of primaquine with activity against pre-erythrocytic (liver) and erythrocytic (asexual) forms as well as gametocytes of Plasmodium species that include Plasmodium vivax (P. vivax) and Plasmodium falciparum. It has been developed by GlaxoSmithKline (formerly SmithKline Beecham) for the radical cure of P. vivax malaria and by 60 Degrees Pharmaceuticals for the prophylaxis of malaria. The exact mechanism(s) of action underlying the anti-Plasmodium activity of tafenoquine are unknown, although it may exert its effect by inhibiting haematin polymerization and, additionally, by inducing mitochondrial dysfunction leading to the apoptotic-like death of the organism. In July 2018, tafenoquine was approved in the USA for the radical cure of P. vivax malaria in patients aged ≥ 16 years who are receiving appropriate antimalarial therapy for acute P. vivax malaria. Subsequently, in August 2018, tafenoquine was approved in the USA for the prophylaxis of malaria in patients aged ≥ 18 years. This article primarily summarizes the milestones in the development of tafenoquine leading to its first global approval for the radical cure of P. vivax malaria.

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References

  1. Crockett M, Kain KC. Tafenoquine: a promising new antimalarial agent. Expert Opin Investig Drugs. 2007;16(5):705–15.

    Article  CAS  Google Scholar 

  2. Campo B, Vandal O, Wesche DL, et al. Killing the hypnozoite—drug discovery approaches to prevent relapse in Plasmodium vivax. Pathog Glob Health. 2015;109(3):107–22.

    Article  CAS  Google Scholar 

  3. Ebstie YA, Abay SM, Tadesse WT, et al. Tafenoquine and its potential in the treatment and relapse prevention of Plasmodium vivax malaria: the evidence to date. Drug Des Dev Ther. 2016;10:2387–99.

    Article  CAS  Google Scholar 

  4. Adis Insight. Drug profile: tafenoquine; 2018.

  5. GlaxoSmithKline. KRINTAFEL (tafenoquine) tablets, for oral use: US prescribing information. 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210795s000lbl.pdf. Accessed 9 Aug 2018.

  6. Food and Drug Administration. NDA210795, NDA approval letter dated 07/20/2018. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2018/210795Orig1s000Ltr.pdf. Accessed 9 Aug 2018.

  7. Medicines for Malaria Venture, GlaxoSmithKline. US FDA approves Krintafel (tafenoquine) for the radical cure of P. vivax malaria [media release]. 20 Jul 2018. http://www.gsk.com.

  8. 60 Degrees Pharmaceuticals. US Food and Drug Administration approves ARAKODA™ (tafenoquine) tablets for oral use; first preventative antimalarial approved in almost two decades [media release]. 9 Aug 2018. http://www.60degreespharma.com.

  9. 60 Degrees Pharmaceuticals LLC. ARAKODA™ (tafenoquine) tablets, for oral use: US prescribing information. 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210607lbl.pdf. Accessed 9 Aug 2018.

  10. GlaxoSmithKline. GSK submits regulatory application for single-dose tafenoquine for the treatment of Plasmodium vivax malaria to Australia’s Therapeutic Goods Administration [media release]. 15 Dec 2017. http://www.gsk.com.

  11. 60 Degrees Pharmaceuticals (60P) media center (Press). 28 Apr 2015. https://60degreespharma.com.

  12. Knight. Knight takes right angle with 60 Degrees Pharmaceuticals LLC [media release]. 11 Dec 2015. http://www.gud-knight.com.

  13. Dow G, Smith B. The blood schizonticidal activity of tafenoquine makes an essential contribution to its prophylactic efficacy in nonimmune subjects at the intended dose (200 mg). Malar J. 2017;16(1):209.

    Article  Google Scholar 

  14. Fukuda MM, Krudsood S, Mohamed K, et al. A randomized, double-blind, active-control trial to evaluate the efficacy and safety of a three day course of tafenoquine monotherapy for the treatment of Plasmodium vivax malaria. PLoS One. 2017;12(11):e0187376.

    Article  Google Scholar 

  15. Green JA, Mohamed K, Goyal N, et al. Pharmacokinetic interactions between tafenoquine and dihydroartemisinin–piperaquine or artemether–lumefantrine in healthy adult subjects. Antimicrob Agents Chemother. 2016;60(12):7321–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. FDA. FDA briefing document: tafenoquine tablet, 150 mg_Meeting of the Antimicrobial Drugs Advisory Committee (AMDAC). 2018. https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/anti-infectivedrugsadvisorycommittee/ucm612874.pdf. Accessed 9 Aug 2018.

  17. Lanners HN. Effect of the 8-aminoquinoline primaquine on culture-derived gametocytes of the malaria parasite Plasmodium falciparum. Parasitol Res. 1991;77(6):478–81.

    Article  CAS  Google Scholar 

  18. Carvalho L, Luque-Ortega JR, Manzano JI, et al. Tafenoquine, an antiplasmodial 8-aminoquinoline, targets leishmania respiratory complex III and induces apoptosis. Antimicrob Agents Chemother. 2010;54(12):5344–51.

    Article  CAS  Google Scholar 

  19. Carvalho L, Martinez-Garcia M, Perez-Victoria I, et al. The oral antimalarial drug tafenoquine shows activity against Trypanosoma brucei. Antimicrob Agents Chemother. 2015;59(10):6151–60.

    Article  CAS  Google Scholar 

  20. Vennerstrom JL, Nuzum EO, Miller RE, et al. 8-Aminoquinoline derivatives against blood stage Plasmodium falciparum in vitro inhibit hematin polymerization. Antimicrob Agents Chemother. 1999;42:598–602.

    Article  Google Scholar 

  21. Al Mamun Bhuyan A, Bissinger R, Stockinger K, et al. Stimulation of suicidal erythrocyte death by tafenoquine. Cell Physiol Biochem. 2016;39(6):2464–76.

    Article  CAS  Google Scholar 

  22. Waters NC, Edstein MD. 8-Aminoquinolines: primaquine and tafenoquine. In: Staines H, Krishna S, editors. Treatment and prevention of malaria: antimalarial drug chemistry, action and use. Basel: Springer; 2012. p. 69–94.

    Google Scholar 

  23. Rueangweerayut R, Bancone G, Harrell EJ, et al. Hemolytic potential of tafenoquine in female volunteers heterozygous for glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PD Mahidol variant) versus G6PD-normal volunteers. Am J Trop Med Hyg. 2017;97(3):702–11.

    Article  CAS  Google Scholar 

  24. Green JA, Patel AK, Patel BR, et al. Tafenoquine at therapeutic concentrations does not prolong Fridericia-corrected QT interval in healthy subjects. J Clin Pharmacol. 2014;54(9):995–1005.

    Article  CAS  Google Scholar 

  25. Miller AK, Harrell E, Ye L, et al. Pharmacokinetic interactions and safety evaluations of coadministered tafenoquine and chloroquine in healthy subjects. Br J Clin Pharmacol. 2013;76(6):858–67.

    Article  CAS  Google Scholar 

  26. Llanos-Cuentas A, Lacerda MV, Rueangweerayut R, et al. Tafenoquine plus chloroquine for the treatment and relapse prevention of Plasmodium vivax malaria (DETECTIVE): a multicentre, double-blind, randomised, phase 2b dose-selection study. Lancet. 2014;383(9922):1049–58.

    Article  CAS  Google Scholar 

  27. US National Institutes of Health. ClinicalTrials.gov identifier NCT01376167. 2018. https://clinicaltrials.gov. Accessed 10 Aug 2018.

  28. US National Institutes of Health. ClinicalTrials.gov identifier NCT02216123. 2018. https://clinicaltrials.gov. Accessed 10 Aug 2018.

  29. GlaxoSmithKline. Krintafel (tafenoquine succinate tablets) FDA Advisory Committee Briefing Document. 2018. https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/anti-infectivedrugsadvisorycommittee/ucm612875.pdf. Accessed 9 Aug 2018.

  30. Tenero D, Green JA, Goyal N. Exposure-response analyses for tafenoquine after administration to patients with Plasmodium vivax malaria. Antimicrob Agents Chemother. 2015;59(10):6188–94.

    Article  CAS  Google Scholar 

  31. Walsh DS, Looareesuwan S, Wilairatana P, et al. Randomized dose-ranging study of the safety and efficacy of WR 238605 (tafenoquine) in the prevention of relapse of Plasmodium vivax malaria in Thailand. J Infect Dis. 1999;180(4):1282–7.

    Article  CAS  Google Scholar 

  32. Walsh DS, Wilairatana P, Tang DB, et al. Randomized trial of 3-dose regimens of tafenoquine (WR238605) versus low-dose primaquine for preventing Plasmodium vivax malaria relapse. Clin Infect Dis. 2004;39(8):1095–103.

    Article  CAS  Google Scholar 

  33. Dow GS, Liu J, Lin G, et al. Summary of anti-malarial prophylactic efficacy of tafenoquine from three placebo-controlled studies of residents of malaria-endemic countries. Malar J. 2015;14:473.

    Article  Google Scholar 

  34. Novitt-Moreno A, Ransom J, Dow G, et al. Tafenoquine for malaria prophylaxis in adults: an integrated safety analysis. Travel Med Infect Dis. 2017;17:19–27.

    Article  Google Scholar 

  35. Nasveld PE, Edstein MD, Reid M, et al. Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects. Antimicrob Agents Chemother. 2010;54(2):792–8.

    Article  CAS  Google Scholar 

  36. Dow GS, McCarthy WF, Reid M, et al. A retrospective analysis of the protective efficacy of tafenoquine and mefloquine as prophylactic anti-malarials in non-immune individuals during deployment to a malaria-endemic area. Malar J. 2014;13:49.

    Article  Google Scholar 

  37. US National Institutes of Health. ClinicalTrials.gov identifier NCT02658435. 2018. https://clinicaltrials.gov. Accessed 10 Aug 2018.

  38. Data on file, GlaxoSmithKline. 2018.

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    James E. Frampton

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  1. James E. Frampton
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Correspondence to James E. Frampton.

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The preparation of this review was not supported by any external funding.

Conflict of interest

During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. James Frampton is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

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This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch and beyond.

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Frampton, J.E. Tafenoquine: First Global Approval. Drugs 78, 1517–1523 (2018). https://doi.org/10.1007/s40265-018-0979-2

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