A small-scale clinical study has shown that a new class of antimalarial drug can safely and quickly kill malaria parasites in the blood. Published today in Science Translational Medicine, these early clinical results open the door to much-needed treatment options to fight against malaria infections as cases of drug resistance continue to rise.
“Malaria continues to be responsible for a large global health burden, with an estimated 282 million cases and 610,000 deaths in 2024,” write the authors of the study, led by Stephan Chalon, MD, PhD, vice president of experimental medicine and clinical pharmacology at the nonprofit organization Medicines for Malaria Venture. “Fast-acting antimalarial drugs are needed to address the emergence of artemisinin resistance in Plasmodium falciparum, the major cause of severe malaria worldwide.”
Malaria infections caused by P. falciparum are typically treated with artemisinin-based combination therapy (ACT). As part of this first-line treatment, an artemisinin-derived drug dramatically reduces the numbers of malaria parasites circulating in the blood within a few hours while a companion drug with a slower mode of action eliminates the remaining parasites.
However, artemisinin-resistant malaria infections have been steadily increasing in Southeast Asia, and more recently in East Africa. As resistance spreads, the efficacy of first-line ACT progressively declines, driving an urgent need for fast-acting alternatives to artemisinin-based drugs.
The clinical trial evaluated the safety and tolerability of MMV367, an oral antimalarial drug candidate under development at Medicines for Malaria Venture. The drug belongs to the pyrrolidinamide class, a novel group of fast-acting antimalarials that interfere with two enzymes that are essential for malaria parasites to synthesize long-chain fatty acids.
As part of the study, 12 healthy volunteers were inoculated with P. falciparum and then treated with MMV367 after eight days. Results showed that doses of 20mg or above were able to quickly kill the parasites, with half of them being eliminated within 4.3 hours. The drug also proved safe in all participants, showing only mild side effects in some of them.
No evidence of emerging drug resistance against this novel drug class was found during the study. However, this will need to be confirmed in future studies with a larger patient population and longer follow-up period. While more research will be needed before this drug can reach people affected by malaria worldwide, these early clinical results support its potential as an alternative to artemisinins in antimalarial combination therapies as they increasingly lose efficacy in the face of escalating drug resistance.
As a product development partnership (PDP), Medicines for Malaria Venture works together with major pharmaceutical companies and academic institutions to promote the development of accessible and affordable medicines to treat and prevent malaria with a major focus on addressing the needs of children and pregnant women. Since its inception in 1999, the nonprofit has delivered 19 approved medicines, with many other candidates currently at various stages of clinical development.
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