MMV: Partnering to Prevent Malaria Relapse with a Single-Dose Treatment

Products: Tafenoquine

Product Type: Drug

Disease: Malaria

Plasmodium vivax causes between 4.5 and  5.5 million clinical infections every year worldwide.[i] Just under a half of these infections occur in South East Asia, and P. vivax is the dominant species in the Americas where it accounts for over 70 per cent of cases.[i] P. vivax is particularly debilitating because this species of parasite can lie dormant in the liver, reactivating to trigger multiple episodes of malaria weeks, months, or even years after the initial mosquito bite. These relapses not only cause further illness for the individual, but also perpetuate the cycle of onward transmission of parasites back into the mosquito. Owing to this relapsing nature, P. vivax malaria poses a substantial economic burden on families and nations and represents a significant challenge for countries pressing toward malaria elimination.[ii]

Until recently, primaquine (PQ) was the only available treatment for preventing relapses of P. vivax malaria. However, ensuring patient compliance to its 7- to 14-day treatment regimen, given that symptoms resolve after the first few days, is difficult, and low compliance can compromise therapeutic efficacy. A medicine with a reduced dosing schedule to improve compliance was therefore urgently needed.

In 2018, single-dose tafenoquine (TQ; Kozenis/Krintafel),[iii] developed through a Medicines for Malaria Venture (MMV) and GlaxoSmithKline (GSK) partnership, became the first new treatment for the prevention of relapse of P. vivax malaria in more than 60 years—and the first-ever single-dose treatment for this indication. TQ was approved by both the U.S. Food and Drug Administration and the Australian Therapeutic Goods Administration (TGA) in 2018 for adults and adolescents from 16 years of age, marking a major regulatory milestone for P. vivax elimination efforts. It has subsequently been registered in Brazil, Colombia, Peru, the Philippines and Thailand with further registrations pending in other endemic countries. In March 2022 the Australian TGA approved the use of single-dose tafenoquine in children aged 2 years and above in combination with chloroquine for the radical cure of P. vivax malaria. This includes a new child-friendly formulation developed specifically to facilitate use in children. MMV and GSK are working together to expand the registration of single-dose tafenoquine to endemic countries.

“Globally, the human and economic cost of relapsing malaria is high. Each malaria episode keeps a child from school or an adult from work, and in susceptible individuals the disease can potentially be fatal. Moreover, as gains are made against the other key malaria parasite, P. falciparum, we’re seeing the proportion of cases of P. vivax increase. As a single dose medicine, we hope that tafenoquine will increase patient adherence and help endemic countries move closer to malaria elimination. We are proud to have worked side-byside with GSK for more than a decade to reach this point. Our focus is now on working to ensure the medicine reaches the vulnerable patients that need it most.”

—DR DAVID REDDY, CEO, MMV

Both PQ and TQ, however, can lead to the destruction of red blood cells (haemolysis) in patients with a specific enzyme deficiency (known as glucose-6-phosphate dehydrogenase or G6PD deficiency). To enable TQ and PQ to be administered only to patients with adequate G6PD enzyme levels, the sister organization and fellow PDP, PATH, has been working to co-develop a point-of-care G6PD diagnostic test with SD Biosensor, a South Korean company. The test is now also enabling countries to expand access to appropriate relapse prevention through their national health systems and support national efforts to eliminate P. vivax.

To find out more about the real world roll out of single-dose tafenoquine with G6PD testing, please watch this short film made in the Brazilian Amazon in 2022: https://youtu.be/2fYONjPJKA0

i. World malaria report 2020. Geneva: World Health Organization; 2020. Licence: CC BY-NC-SA 3.0 IGO.

ii. P. vivax relapses. Vivaxmalaria.org. https://www.vivaxmalaria.org/p-vivax/p-vivax-relapses. Accessed October 2020

iii. Tafenoquine is marketed as Kozenis in Australia and Krintafel in the USA. Trademarks are owned or licensed to the GSK group of companies.