Tafenoquine has performed comparably with primaquine in terms of hemoglobin level decrease in individuals with malaria and normal glucose-6-phosphate dehydrogenase (G6PD) enzyme levels, according to a study recently published in The New England Journal of Medicine. Despite not achieving noninferiority to primaquine, tafenoquine performed well in curing Plasmodium vivax malaria.

This phase 3, double-blind, randomized controlled trial included 251 participants with P vivax malaria, 166 of whom were treated with a single tafenoquine 300-mg dose and 85 of whom were treated with primaquine 15 mg once daily for 2 weeks (2:1 random assignment). Participants were at least 16 years old and lived in Vietnam, Thailand, Peru, Colombia, and Brazil. Inclusion criteria were ≥40% of normal G6PD enzyme levels for women and ≥70% of normal levels for men. A chloroquine course was administered to all participants. Follow-up lasted 6 months. A reduction in hemoglobin of at least 3.0 g/dL to less than 6.0 g/dL or at least 30% from baseline was defined as the study’s primary safety outcome. In terms of efficacy, the primary outcome was no relapse of P vivax parasitemia throughout follow-up. Non-inferiority was defined as an odds ratio of 1.45 for tafenoquine vs primaquine.

Among participants in the tafenoquine group, 2.4% (95% CI, 0.9-6.0%) had a reduction in hemoglobin consistent with study protocol, while 1.2% (95% CI, 0.2-6.4%) showed a reduction in the primaquine group. This outcome occurred only among male participants with normal genotype and phenotype of G6PD. At 6 months in the GATHER trial, 74.1% of the per-protocol tafenoquine group and 76.0% of the primaquine group were recurrence-free. Meta-analysis of both the GATHER and DETECTIVE trials yielded 69.1% non-recurrence in the tafenoquine group and 73.2% non-recurrence in the primaquine group. Tafenoquine did not demonstrate noninferiority to primaquine in terms of efficacy (recurrence odds ratio, 1.81; 95% CI, 0.82-3.96).

Limitations to this study included variability by region, which resulted from the data of just 2 studies.

The study researchers conclude that “[among] patients with normal G6PD enzyme activity, the decline in hemoglobin level with tafenoquine did not differ significantly from that with primaquine. Tafenoquine showed efficacy for the radical cure of P vivax malaria, although tafenoquine was not shown to be noninferior to primaquine.”

This study received funding from Medicines for Malaria Venture and GlaxoSmithKline,  a pharmaceutical company. For a full list of author disclosures, visit the reference.

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Llanos-Cuentas A, Lacerda MVG, Hien TT, et al. Tafenoquine versus primaquine to prevent relapse of Plasmodium vivax malaria. N Engl J Med. 2019; 380:229-241