WHO and national treatment guidelines recommend treating both the blood- and liver-stage of P. vivax malaria. However, physicians do not always prescribe primaquine, the only medicine currently available for the treatment of liver-stage infections. Several factors contribute to the low use of primaquine, including: concerns about possible haemolysis in G6PD1-deficient patients, limited access to G6PD tests, and poor compliance with the 14-day course of treatment.
MMV is working with GSK on the development of tafenoquine as a single-dose treatment for the radical cure of liver-stage infections. While tafenoquine shares similar limitations with primaquine regarding use in G6PD-deficient patients, its simplified dosing regimen and single dose (instead of 14 days of primaquine) should improve real-life treatment compliance and drug effectiveness.
The phase III clinical trials of tafenoquine have been completed; top line results were presented at the 6th International Conference on Plasmodium vivax Research in Manaus, Brazil on 12 June 2017, and demonstrated clear superiority of single-dose tafenoquine plus 3-days of chloroquine compared to P. vivax treatment with 3-days of chloroquine alone. The regulatory dossier for tafenoquine was submitted to the US FDA and separately to the Australian TGA in Q4 2017.
Recruitment for the first cohort of a paediatric PK bridging study is complete and the analysis of the data is complete; recruitment of the second cohort started in January 2018.
In parallel, PATH is working with industry partners to develop a point-of-care G6PD test to ensure that only patients with adequate level of G6PD enzymatic activity will receive tafenoquine.
Access in Action
MMV has worked with GSK to disseminate the results of the phase III programme to WHO’s Global Malaria Programme, as well as key P. vivax experts. These data were also shared during a stakeholder side event organized at the 6th International Conference on Plasmodium vivax Research, with country representatives and key opinion leaders and during the ASTMH annual conference organised in Baltimore on November 2017.
MMV, PATH and GSK have engaged with the National Malaria Control Programme management in Brazil and Thailand to understand country requirements in preparation for the introduction of tafenoquine + a G6PD diagnostic test (“The Tafenoquine Proposition”). In parallel, MMV and PATH visited point-of-care malaria treatment centres to understand how malaria control services are provided and organized at various levels within the health system, including diagnosis, treatment, supply chain, training and pharmacovigilance.
As the country facing the highest burden of P. vivaxin Africa, Ethiopia in recent years has begun to take on the challenge of providing radical cure on a systematic basis to patients with confirmed P. vivax infections. In 2017, MMV and WHO worked together collaboratively with Ethiopia’s Ministry of Health to convene a planning meeting focused on the roadmap for expanding access to radical cure in the coming years in Ethiopia.
GlaxoSmithKline (GSK), PATH
1. G6PD deficiency is an inherited abnormality that causes the loss of a red blood cell enzyme. In people with G6PD deficiency, WHO recommends preventing relapse by giving primaquine base at 0.75 mg/kg body weight once a week for 8 weeks, with close medical supervision for potential primaquine-induced haemolysis. (WHO GMP: Testing for G6PD deficiency for safe use of primaquine in radical cure of P. vivax and P. ovale malaria)
Updated April 2018