WEHI, MSD's antimalarial drug candidate enters Phase 1 trial
A new antimalarial drug candidate, discovered by WEHI and global biopharmaceutical company MSD, has entered Phase 1 clinical testing in healthy participants.
Pre-clinical studies have shown the candidate can inhibit growth of the malaria parasite and prevent transmission through the mosquito, reducing spread of the disease.
The initial first-in-human study is designed to assess safety, tolerability and pharmacokinetics. The results from this study will inform the need for clinical development of this compound.
In pre-clinical studies the dual-targeting mechanism appears to confer a high barrier to the generation of resistance, an important criterion for malaria drug candidates.
Professor Alan Cowman, an international malaria expert who recently won the CSL Florey Medal for his outstanding research contributions to the field, said that the preclinical profile observed to date makes it a promising new antimalarial drug candidate.
“In pre-clinical studies we’ve shown this compound inhibits two enzymes that process and activate key proteins that enable the parasites to move in and out of red blood cells,” Cowman, deputy director at WEHI and a Laboratory Head in the Infectious Diseases and Immune Defence Division, said.
“The pre-clinical studies indicate that inhibiting these two enzymes — Plasmepsin IX (PMIX) and Plasmepsin X (PMX) — effectively disables the parasite from carrying out its key function of replicating and multiplying in the bloodstream.
“The successful initiation of these first-in-human trials is an important milestone towards developing urgently needed new treatments that could alleviate this major global health burden.”
Targeting drug resistance
As new malaria parasites increasingly become resistant to available drugs, the development of vaccines and novel antimalarial compounds to block transmission is vital in the fight against this killer disease.
MSD scientist and US team lead Dr David Olsen said: “Efforts to develop drugs for malaria typically focus on disrupting a novel parasitic process or pathway to avoid pre-existing drug resistance and, ideally, are active at multiple stages of the lifecycle.
“By inhibiting two essential parasitic enzymes, this molecule met both criteria with the potential to provide a high barrier for the development of drug resistance.”
The compound is the result of an eight-year collaboration between WEHI and MSD, dedicated to discovering new widely applicable malaria drug candidates.
In 2022, the research collaboration published findings from preclinical experiments that revealed how a new class of antimalaria compounds worked to stop parasites from spreading in the blood.
The team plans to present the results from this initial clinical trial at a future scientific meeting and further clinical trials are being planned.
The project was supported by the Wellcome Trust, the Victorian Government and the National Health and Medical Research Council (NHMRC).
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