Two phase III trials of tafenoquine show treatment benefits for malaria - GSK and Medicines for Malaria Venture

GSK and Medicines for Malaria Venture announced positive results from two phase III studies of tafenoquine, for the prevention of relapse of Plasmodium vivax (P.vivax) malaria. The headline results show that a single-dose of 300mg tafenoquine, when given with a 3-day blood-stage chloroquine treatment, reduced the risk of relapse in patients with P.vivax malaria significantly more than placebo when given with chloroquine. The two phase III randomised, double-blind studies, �DETECTIVE� and �GATHER�, were conducted in malaria-endemic countries covering South America, Asia, and Africa.

DETECTIVE was a double-blind, double-dummy phase III study evaluating the efficacy, safety and tolerability of tafenoquine in 522 patients with P.vivax malaria. Patients were randomised to receive either a single-dose (1-day) of tafenoquine (300mg), a 14-day course of primaquine (15mg), or placebo, with all patients also receiving a 3-day course of chloroquine to treat the acute blood stage of the infection. The study met its primary endpoint, showing that a statistically significant greater proportion of patients treated with tafenoquine (60%) remained relapse-free over the 6-month follow-up period than patients on placebo (26%). A statistically significant greater proportion of patients treated with 14-days of primaquine (64%) were relapse-free over the 6-month follow-up period than patients on placebo (26%). The frequency of adverse events was 63% for the tafenoquine group, 59% for the primaquine group and 65% for the chloroquine group, and the frequency of serious adverse events was 8% for the tafenoquine group, 3% for the primaquine group and 5% for the chloroquine group.

GATHER was a study in 251 patients investigating a single-dose of 300mg tafenoquine on levels of haemoglobin (a protein in red blood cells that carries oxygen) when compared to a 14-day course of 15mg primaquine, with all patients also receiving a standard 3-day course of chloroquine. The incidence of decline in haemoglobin (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), with the difference in proportions (95% CI) of 1.23%. No patient required a blood transfusion. The frequency of adverse events was 72% for the tafenoquine group and 75% for the primaquine group and the frequency of serious adverse events was 4% for the tafenoquine group and 1% for the primaquine group. Results were presented at the International Conference on Plasmodium vivax Research (ICPVR).