On the heels of this year’s International Conference of Research on Plasmodium vivax Malaria, which was held in Manaus, Brazil, GlaxoSmithKline (GSK) – in collaboration with Medicines for Malaria Venture (MMV) – announced positive outcomes of two Phase III trials of tafenoquine, a novel 8-aminoquinoline currently under evaluation for the prevention of relapsing P. vivax malaria. If approved, GlobalData believes the single-dose tafenoquine could address a clear unmet need, as primaquine, the currently approved compound for preventing P. vivax relapse, requires 14 days of administration, is associated with many side effects, and holds several contraindications.
P. vivax is the second most prevalent species of parasite-causing malaria, and differs from P. falciparum in that it can enter a dormant liver stage called hypnozoites, which can activate and enter the blood stream several months, or even years, after the infecting mosquito bite, causing relapse of malaria. Currently, the World Health Organization (WHO) recommends a 14-day course of primaquine – administered alongside a blood stage agent (artemisinin-based combination therapy [ACT] or chloroquine) – to eradicate the liver stage of the parasite and to prevent relapse of the disease. However, many people find it difficult to adhere to the 14-day primaquine regimen, and the drug carries a potential risk of hemolytic anemia in those with glucose-6-phosphate-dehydrogenase enzyme (G6PD) deficiency.
GSK’s randomized, double-blind, Phase III studies – DETECTIVE and GATHER – showed that a single dose of 300mg of tafenoquine, when administered with a three-day schizonticidal chloroquine treatment, significantly reduced the risk of relapse in patients with P. vivax malaria compared with placebo.
The first Phase IIb/III clinical trial, DETECTIVE, was divided into two parts and included multiple experimental arms in which subjects ages 16 years and above were administered chloroquine 600mg on Days 1 and 2, and a different dose of tafenoquine on either Day 1 or 2, depending on their eligibility. The study showed that a single dose (300mg or 600mg) of tafenoquine had better efficacy than chloroquine alone and chloroquine plus primaquine in preventing relapsing P. vivax malaria.
Similarly, GATHER investigated a single dose of 300mg tafenoquine on levels of hemoglobin when compared to a 14-day course of 15mg primaquine, with all 251 patients also receiving a standard
three-day course of chloroquine. The incidence of decline in hemoglobin – the primary endpoint – was very low, and similar between the two treatment groups (2.4% for patients receiving tafenoquine and chloroquine vs. 1.2% for patients receiving primaquine with chloroquine), and no patient required a blood transfusion.
With an estimated number of symptomatic cases surpassing 15 million per year globally, P. vivax malaria often requires follow-up visits to avoid relapses and complications, in addition to conventional ACT. Moreover, one of the main concerns associated with malaria is the development of drug resistance, which may occur when a patient does not fully adhere to the treatment regimen. GlobalData believes that GSK’s tafenoquine could bring an added value to the current prevention landscape as a solid improvement over primaquine, with the potential to strongly contribute to the eradication of the mosquito-borne disease in conjunction with other strategies.