To stem the emergence of malaria drug resistance, the WHO recommends the use of a combination of drugs that act in different ways. The current artemisinin-based combination therapies (ACTs) must be taken once or twice daily over a period of 3 days. Several studies have shown that patients often do not adhere to, or complete, the recommended regimen, which can lead to the emergence of drug-resistant parasites.1
Multidrug-resistant malaria has already emerged in the Greater Mekong Sub-region of Southeast Asia, resulting in high levels of treatment failure.2,3 Current short-term efforts to manage drug-resistant infections involve the use of longer treatment courses and studies are ongoing to explore the use of triple combinations. In the longer term, new medicines with novel mechanisms of action are needed to ensure malaria can continue to be cured in the face of increasing drug resistance.
MMV prioritizes the development of new therapies with novel mechanisms of action, activity against all known resistant parasite strains and more convenient treatment regimens.
In line with its target product profiles (TPPs), MMV is developing next-generation combination therapies that have the potential to be ‘single- or multiple-encounter radical cures’ (SERC or MERC). It is important that such drug combinations quickly kill and clear all parasites, demonstrate activity against all known resistant strains, be well tolerated and have a simple dosing regimen.
By improving compliance, the medicine would, in turn, help improve clinical management. An ideal medicine would also have the potential to block transmission, prevent relapse and provide chemoprotection, which would also help reduce the overall burden of malaria.
Within MMV’s portfolio, two new combinations have reached phase IIb development – artefenomel/ferroquine and KAF156/lumefantrine. Both of these combinations have the potential to meet this target and both are being tested against all known multidrug-resistant malaria parasites. It is hoped these new drug combinations will one day be at the front line of antimalarial treatment.
As with the current ACTs, future medicines should be based on a combination of two or more compounds. MMV and its partners are undertaking non-clinical, combination studies earlier in the drug development pathway than has historically been the case. These studies are providing information on the compatibility of candidate compounds and predictions on their dose and efficacy as partner molecules. Read more about identifying optimal drug combinations.
Bruxvoort K et al. “How Patients Take Malaria Treatment: A Systematic Review of the Literature on Adherence to Antimalarial Drugs.” PLoS One. 9(1):e84555 (2014).
Dondorp AM et al. “How to Contain Artemisinin- and Multidrug-Resistant Falciparum Malaria.” Trends Parasitol.
Imwong M et al. “The spread of artemisinin-resistant Plasmodium falciparum in the Greater Mekong subregion: a molecular epidemiology observational study.” Lancet Infect Dis. 17(5):491–497 (2017).