New developments in anti-malarial target candidate and product profiles

Abstract

A decade of discovery and development of new anti-malarial medicines has led to a renewed focus on malaria elimination and eradication. Changes in the way new anti-malarial drugs are discovered and developed have led to a dramatic increase in the number and diversity of new molecules presently in pre-clinical and early clinical development. The twin challenges faced can be summarized by multi-drug resistant malaria from the Greater Mekong Sub-region, and the need to provide simplified medicines. This review lists changes in anti-malarial target candidate and target product profiles over the last 4 years. As well as new medicines to treat disease and prevent transmission, there has been increased focus on the longer term goal of finding new medicines for chemoprotection, potentially with long-acting molecules, or parenteral formulations. Other gaps in the malaria armamentarium, such as drugs to treat severe malaria and endectocides (that kill mosquitoes which feed on people who have taken the drug), are defined here. Ultimately the elimination of malaria requires medicines that are safe and well-tolerated to be used in vulnerable populations: in pregnancy, especially the first trimester, and in those suffering from malnutrition or co-infection with other pathogens. These updates reflect the maturing of an understanding of the key challenges in producing the next generation of medicines to control, eliminate and ultimately eradicate malaria.

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“…The target candidate and product profiles for antimalarials were recently updated with particular emphasis on elimination and eradication scenarios, 6 which requires candidates with chemoprophylactic activity, a drug class with a comparatively dry pipeline until recently 7 . One compound, tafenoquine, has been in late-stage clinical development for more than 15 years 8 .…”

Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes

“…Even more importantly, it means that most genes must function at multiple points in the life cycle, which helps rationalize why many antiplasmodial compounds discovered through their ability to kill cultured blood stages can also function as the multi-stage drugs now considered crucial for malaria eradication (Burrows et al., 2017). Recent progress in this area can now be understood in the light of a high degree of genetic essentiality in the Plasmodium genome.…”

Safety, tolerability, pharmacokinetics, and activity of the novel long-acting antimalarial DSM265: a two-part first-in-human phase 1a/1b randomised study

“…The target product profile of an antimalarial drug is a combination therapy that would increase compliance, potentially allowing directly observed therapy, and prevent transmission 7 . This profile would imply shortening the course of therapy from 3 days preferably to a single dose.…”