Image by Mae Melvin
Blood smear showing
A single dose of tafenoquine, when given with chloroquine, can significantly reduce the risk of relapse in patients with Plasmodium vivax malaria compared to placebo, as demonstrated by the results of 2 phase 3 studies.
Patients who have had P vivax malaria, even a single infection, can relapse several weeks or even years after the initial occurrence.
Results of the studies were presented at the 6th International Conference on Plasmodium vivax Research (ICPVR) in Manaus, Brazil.
Tafenoquine, an 8-aminoquinoline derivative, is being developed by GlaxoSmithKline (GSK) in collaboration with Medicines for Malaria Venture (MMV).
“One of the greatest challenges for patients with P vivax malaria,” Patrick Vallance, of GSK, said, “is preventing relapses.”
“Being able to treat patients with a single dose of medicine would be an important step forward in ensuring efficacious treatment,” Vallance noted, “thereby reducing the risk of relapse, particularly in areas with very limited healthcare infrastructure.”
The DETECTIVE and GATHER studies were conducted in malaria-endemic countries in South America, Asia, and Africa.
DETECTIVE (TAF112582) study
This was a double-blind, double-dummy phase 3 study evaluating the efficacy, safety, and tolerability of tafenoquine in 522 patients aged 16 years or older with P vivax malaria.
Patients were randomized to receive placebo, a single dose of 300 mg tafenoquine, or primaquine at 15 mg daily for 14 days in a 1:2:1 ratio.
All patients received a 3-day course of chloroquine to treat the acute blood stage infection.
The study met its primary endpoint. 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%). The odds ratio for risk of relapse vs placebo given with chloroquine was 0.24, P<0.001.
Treatment with 14 days of primaquine also achieved a statistically significant improvement in relapse-free follow-up, with an odds ratio vs placebo when given with chloroquine of 0.20, P<0.001.
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 (TAF116564) study
This study evaluated a single dose of 300 mg tafenoquine on hemoglobin levels compared to a 14-day course of 15 mg primaquine.
Agents in the 8-aminoquinoline drug class are associated with hemolytic anemia in individuals with inherited glucose-6-phosphate dehydrogenase (G6PD) deficiency.
All patients were screened for G6PD deficiency at baseline. Males with G6PD activity of at least 70% of the site median and females with 40% were eligible.
All 251 patients also received the standard 3-day course of chloroquine.
The incidence of decline in hemoglobin was low and similar between the 2 treatment arms, 2.4% for the tafenoquine group and 1.2% for the chloroquine group.
No patient required a blood transfusion.
The companies plan to develop a point-of-care diagnostic for G6PD as a mandatory test prior to treatment with tafenoquine.
“The positive results of the phase 3 trials for single-dose tafenoquine provide great hope that a new, effective drug to stop the relapse of P vivax malaria is in sight,” David Reddy, of MMV, affirmed.
Tafenoquine currently is not approved for use anywhere in the world. GSK plans to submit regulatory filings later in 2017.
