Malaria medicines: a glass half full?

Key Points Antimalarial drug discovery has substantially contributed to the gains achieved against malaria over the past two decades. However, this progress and achieving the United Nations' Millennium Goals as they relate to malaria are both being threatened by emerging drug resistance, and major gaps persist for most target compound profiles. Over the past decade, new, less costly and more sophisticated phenotypic screens have been developed, resulting in new drug candidates and antimalarial targets. Many of these molecules are now entering clinical development. Four new molecules with unprecedented modes of action are currently in Phase II trials for blood-stage treatments: KAE609 (also known as cipargamin), OZ439 (also known as artefenomel), KAF156 (also known as GNF156) and DSM265. Each of these has the potential to shorten the current 3-day regimen of artemisinin combination therapies. Significant contributions to the antimalarial drug discovery pipeline are being made by companies, academic institutions and non-profit organizations located in malaria-endemic countries. Moreover, Phase I studies are now being performed in populations that most need these antimalarials. A new translational tool has been developed whereby antimalarial pharmacodynamics is studied in subclinically infected volunteers. The model is now routinely used for evaluating new drug candidates, resulting in significant time and cost savings for development. Clinical efforts are needed to develop treatments for vulnerable populations such as young children and expectant mothers, and for chemoprotection. Efforts are also needed for drugs that target the liver schizont stage of malaria parasites and for preventing transmission. Progress has been made in early open-access drug discovery, with increased availability of proprietary compounds for screening assays. Despite considerable advances in malaria medicines in the past 20 years, the global burden of malaria remains substantial. Moreover, continued emergence of drug resistance ensures that new antimalarials will be needed in the near future. Wells and colleagues summarize the current landscape of antimalarial therapies and investigational drugs, highlighting the progress made, identifying gaps in terms of target profiles and recommending priorities for future research. Despite substantial scientific progress over the past two decades, malaria remains a worldwide burden that causes hundreds of thousands of deaths every year. New, af