Malaria - tafenoquine
Malaria is a major killer in sub-Saharan Africa, affecting 300m people, and killing an estimated 1m children every year.
Malaria is a major killer in sub-Saharan Africa, affecting 300m people, and killing an estimated 1m children every year.
The malaria parasite is becoming increasingly resistant to the cheap, readily available drugs, such as chloroquine and sulfadoxine-pyrimethamine that are commonly used to treat it. Newer medicines, such as the artemisenin based combination therapies and GSK's newly approved LapDap are much more effective, but the need for additional therapies to combat resistant organisms remains.
Another agent, primaquine, is the drug of choice to eliminate latent liver forms of the malaria parasite, but resistance is building here, too. A new agent that acts at this stage, tafenoquine, has been developed by the Walter Reed Army Institute of Research in Washington DC, US, and licensed to GlaxoSmithKline.
A human challenge model was used to investigate its potential.1 Four subjects were given a single oral dose of 600mg tafenoquine, and two placebo, prior to a challenge with mosquitoes infected with the malaria parasite Plasmodium falciparum. Three of the four given the active were protected, and the fourth developed malaria, as did both of those given placebo.
A randomised double blind study was carried out in an area of Gabon where P. falciparum is endemic.2 A total of 410 subjects were given an initial curative regime of halofantine, followed by prophylactic tafenoquine in doses of 31.25, 62.5, 125 or 250mg, or placebo. After 77 days, 34 patients were positive for the parasite, 30 of whom had received placebo or the lowest dose, and none the highest.
A similar placebo-controlled trial was carried out in 235 subjects in Kenya3, where a loading dose followed by various different regimens of tafenoquine were given for up to 13 weeks. Those given the highest doses, 400mg, throughout had the best protection.
It has also been investigated for efficacy as post-exposure prophylaxis4. A total of 586 Australian Defence Force personnel returning from Papua New Guinea were given 22.5mg of primaquine for 14 days, or tafenoquine in doses of 400mg for three days or 200mg twice a day for three days. Within a year, six of those given primaquine had developed malaria, and seven of the 378 who had received tafenoquine. Those given the new drug tended to develop the disease later. Phase III trials are under way, and if successful the drug could be submitted for approval as early as next year.