Reports of the independent emergence of laboratory markers for artemisinin resistance in Rwanda were published in August 2020. While it's important to note that ACTs continue to cure malaria in Africa, these reports reinforce the urgent need for the development and deployment of both mitigation strategies and non-artemisinin drug treatments for malaria.  

With partners, MMV is exploring different mitigation strategies to delay the further development of artemisinin resistance: 

• Adding a single low dose of primaquine to an ACT to block transmission. 
• Multiple first-line treatment: the use of more than one first-line drug simultaneously to reduce the drug pressure on any single medicine. 
• Triple ACT combinations: adding a third drug to an existing combination to maintain efficacy and protect the individual components.  

For the future, new treatments that are not based on artemisinin (the main component of current first-line antimalarials) nor the partner drugs for which resistance has emerged, are urgently needed. MMV’s portfolio includes 14 compounds in clinical development, the majority of which have novel mechanisms of action compared with those used in artemisinin-based combination therapies. 

Under-dosing of antimalarials can result in incomplete cure, which in turn can lead to resistance. MMV is working to develop treatments with simpler dosing regimens, which would help to ensure correct dosing and thereby help to prevent the emergence of future drug resistance.  

First-line treatment for severe malaria (artesunate) is based on artemisinin.To be sure this potentially fatal form of the disease can continue to be cured, MMV is exploring alternatives. Among the molecules in MMV’s pipeline to address this need, KAE609 with Novartis, is in preparation for phase II. 

The current drug regimen to protect children from malaria during the rainy season, sulfadoxine-pyrimethamine + amodiaquine (SPAQ) is also at risk. We already see resistance to SP in eastern and southern Africa. Developing alternative options to protect this vulnerable population is a key MMV priority. 

MMV is looking at new ways to defeat malaria parasites. Up until 2010 there were only five known antimalarial drug targets. Since then, over 50 targets have been validated in vitro of which >30 in vivo or in the clinic – the vast majority have been through MMV and partner collaborations, including the work of the Malaria Drug Accelerator (MalDA) of which MMV is a founder member.   

MMV works with investigators in endemic countries to test new medicines directly on resistant parasites in the laboratory, helping to ensure next generation-medicines are effective for all patients, including those living in resistance zones. 

MMV strives to minimize the impact of emerging resistance on its portfolio. At candidate selection, data is available on cross resistance with other antimalarials as well as the mechanism and frequency of resistance. These data serve as criteria for down-selecting a compound for development for treatment. Furthermore, MMV prioritizes chemical scaffolds for drug discovery that are ‘irresistible’, in the sense that it has not been possible to generate resistance to them in the laboratory under standard in vitro conditions. 

According to the latest WHO World Malaria Report, progress against malaria is stalling and sustained commitment is needed if we are to reach the 2030 goal of reducing incidence and mortality by 90%. New drugs, however, are in development and if approved, will help accelerate progress towards these ambitious global malaria goals.