Single-Dose Tafenoquine Could Prevent Relapse of P vivax Malaria

February 12, 2019
Jonna Lorenz

Single-dose tafenoquine shows promise for the radical cure of P vivax malaria, according to two new studies published in the New England Journal of Medicine.

Single-dose tafenoquine is showing great promise for the treatment of malaria, and a new study found that it significantly lowered the risk of recurrence of Plasmodium vivax malaria, which is known to lay latent and undetectable in the liver.

"[T]he risk of P vivax recurrence from any cause was about 70% lower with tafenoquine than with placebo over the 6-month trial period," the investigators wrote in the study, published in the New England Journal of Medicine. "Given the need to reduce the global burden of P vivax malaria, GlaxoSmithKline will make tafenoquine available at an affordable price in countries in which malaria is endemic to improve access to those who need it most."

The study, supported by GlaxoSmithKline and conducted in countries where malaria is endemic, was a multicenter, double-blind, double-dummy, parallel group, randomized, placebo-controlled trial. It was led by Marcus V. G. Lacerda, MD, PhD, from the Dr. Heitor Vieira Dourado Tropical Medicine Foundation, and Alejandro Llanos-Cuentas, MD, from Universidad Peruana Cayetano Heredia.

Tafenoquine, like primaquine, causes hemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, and testing should be done before the drug is administered.

Another study led by the same investigators and published in the New England Journal of Medicine compared tafenoquine with primaquine for the radical cure of P vivax malaria, with 69.1% of patients in the tafenoquine group remaining free from recurrence after 6 months and 73.2% of those in the primaquine group remaining free from recurrence.

That study pointed out that while primaquine may have slight efficacy advantage over tafenoquine, the single-dose convenience of tafenoquine gives it an advantage in adherence. Adherence to primaquine is reported to be as low as 24% in Southeast Asia. Both drugs caused slight declines in hemoglobin level among patients with normal G6PD enzyme activity.

A commentary published in the New England Journal of Medicine noted that tafenoquine is restricted to patients with greater than 70% of normal G6PD activity and that a quantitative assessment must be performed before administering the drug. Such tests have not been tested extensively under field conditions.

"The two current studies showed that with appropriate G6PD testing, tafenoquine can be given safely," Nicholas J. White, FRS, of the Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, and the Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom, wrote in the commentary.

Payal Patel, MD, MPH, assistant professor of infectious diseases at University of Michigan and VA Ann Arbor Health System, told Contagion® that having a single-dose option for treatment and prevention may improve morbidity associated with the infection.

"A lot of people just get tired of taking the whole treatment course," Dr. Patel said. "The less amount of medicine that you have to take, the more likely the patient is going to be to take it."

Dr. Patel continued on to explain that US residents who become infected with malaria after traveling to countries where the disease is endemic often haven't taken any prophylaxis, didn't finish their course, or switched treatments.

Single-dose tafenoquine was approved by the US Food and Drug Administration (FDA) last year, with GlaxoSmithKline's Krintafel being the first drug in more than 60 years to be approved for the treatment of P vivax malaria.

A month later, the FDA approved 60 Degrees Pharmaceuticals' Arakoda tafenoquine tablets for malaria prophylaxis in patients 18 years and older.

New drug development for malaria is even more important in light of a recent announcement from the US Centers for Disease Control and Prevention that quinidine, the only FDA-approved antimalarial drug in the United States, has been discontinued and will no longer be available beginning April 1. This will make treating the estimated 300 cases of severe malaria reported in the United States each year even more difficult as providers will have to request IV artesunate from the CDC under an investigational new drug protocol as it is neither FDA approved nor commercially available in the United States.