The wait is over for a new drug to counter Plasmodium vivax malaria relapse. The United States Food and Drug Administration (FDA) has approved, under Priority Review, a 300 mg single-dose tafenoquine (Krintafel, GlaxoSmithKlein) for the radical cure of P. vivax malaria in patients 16 years of age and older who are receiving antimalarial therapy.1
P. vivax malaria is most prevalent across Asia and America, where it causes major health and economic burden.2 The dormant liver stage of P. vivax – known as the hypnozoite – persists in the human liver for extended periods causing clinical relapses weeks, months, or even years later following a single infective mosquito bite.2,3 Hypnozoites are undetectable and represent a reservoir for future malaria transmission in new areas without ongoing transmission. Thus, the radical cure ie, elimination of hypnozoites aims to decrease morbidity and reduce transmission.
The only existing treatment to prevent the relapse of P. vivax malaria – primaquine – was developed more than 60 years ago. This hypnozoitocide drug is typically given in combination with a 3-day therapy of chloroquine which targets the blood stages of P. vivax.3 However, key challenges associated with primaquine treatment are patient adherence due to the drug’s 14-day regimen which leads to reduced efficacy, and serious adverse events reported in some patients.4
Tafenoquine has a long half-life of 14 days compared with primaquine – thus offering a more convenient single-dose regimen to improve patient adherence.3 Tafenoquine is recommended to be co-administered with a standard 3-day chloroquine dose for the liver-stage of P. vivax malaria.4 A phase IIb study reported greater 6-month recurrence-free efficacy in 300 mg tafenoquine plus 3-day chloroquine (89.2%) than in primaquine plus chloroquine (77.3%) and chloroquine alone (37.5%).3 The evidence of clinical efficacy and safety of the 300 mg single-dose tafenoquine was provided by DETECTIVE Part 1 and Part 2, and GATHER – three randomised, double blind studies involving more than 800 participants.5
Tafenoquine is contraindicated for patients who are allergic to any 8-aminoquinoline-containing agents, and those who are glucose-6-phosphate dehydrogenase (G6PD) deficient.1 Patients whose G6PD status is unknown should be tested. Similarly, tafenoquine is also not recommended for women breastfeeding a child with G6PD, or a child whose G6PD status is unknown.
The approval of tafenoquine marks a major milestone and contribution towards global efforts to eradicate malaria.