Developing next-generation medicines to address drug resistance and improve compliance

To stem the emergence of drug resistance and reduce its impact, the World Health Organization (WHO) recommends the use of a combination of two drugs that act in different ways. Recent reports from southeast Asia and along India’s borders1 of parasite strains resistant to both artemisinin and partner drugs, such as mefloquine and piperaquine, are thus of great concern.2 Populations of drug-resistant parasites can lead to an overall reduction in efficacy and treatment failure.3 In the worst case this could lead to an epidemic of drug-resistant malaria. Without new and effective next-generation medicines at hand, we may then start to see a rise in the malaria burden and mortality.

Current artemisinin-based combination therapy (ACT) must be taken once or twice daily over a period of 3 days. Several studies suggest that patients often do not complete the full course of treatment, which can lead to incomplete cure and the appearance of drug-resistant pathogens.4

MMV and partners are prioritizing the development of new therapies to solve the challenges of drug resistance and treatment adherence by identifying molecules with novel mechanisms of action and activity against all known resistant parasite strains. The new molecules either kill the parasite quickly, stay in the blood long enough to ensure complete parasite clearance, and/or can protect against subsequent re-infection. These compounds could form part of a Single Exposure Radical Cure (SERC) – a single-dose combination expected to ensure better compliance.

The longer-term aim is to develop a Single Exposure Radical Cure and Prophylaxis (SERCaP) that would provide some form of additional chemoprotection and be suitable for use in mass drug administration programmes. A Multiple Exposure Radical Cure (MERC)/MERCaP that demonstrates efficacy against key resistant strains may also be considered.

1 Tun KM et al. “Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a crosssectional survey of the K13 molecular marker.” Lancet Infect Dis. 15;415-21 (2015).

2 Yeka A et al. “Efficacy and safety of fixed dose artesunate-amodiaquine vs. artemether-lumefantrine for repeated treatment of uncomplicated malaria in Ugandan children.” PLoS One. 1;9(12);e113311 (2014).

3 Phyo AP et al. “Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study.” Lancet. 379:1960-6 (2012).

4. 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).