Discovering and developing new medicines for malaria control and elimination

Abstract

A steady increase in the number of antimalarial drug candidates since 2007 follows a call to eradicate malaria from the World Health Organization (WHO), the Bill and Melinda Gates Foundation and others. Four new fixed dose combination medicines have been approved by stringent authorities or the WHO in as many years. OZ439, a synthetic endoperoxide currently in Phase II, could reduce treatment to a single dose. Significant challenges remain: while drugs to treat patients suffering from malaria are essential, drugs focused on breaking the lifecycle between human and mosquito host are needed. Effective medicines that are easy to take in the field are needed, together with treatments for infants and for women in the first trimester of pregnancy. Research has concentrated on Plasmodium falciparum infection but there is a need for medicines that prevent relapses of P. vivax infection. In addition, the evolution of pathogen resistance against established drugs poses a threat to existing medicines. Direct testing of compounds against whole parasites as well as target approaches has accelerated the process of drug discovery, and identified new classes of compounds. The most advanced of these, spiroindolone, already in clinical development, kills the blood stages of both P. falciparum and P. vivax by a mechanism unrelated to any current antimalarial. The collaborative model of drug discovery between the Medicines for Malaria Venture, pharmaceutical companies and academic institutions has resulted in the construction of a promising pipeline of new classes of compounds, focused on the needs of the patient.