CUREMAL

The challenge

Malaria remains one of the most serious health threats across much of sub-Saharan Africa. Globally, more than 250 million cases occur each year, leading to an estimated 600,000 deaths annually, mostly in Africa. 

Uncomplicated malaria is typically treated with artemisinin combination therapies (ACTs), pairs of drugs that include derivatives of artemisinin. However, there are growing concerns that malaria parasites are becoming less sensitive to artemisinin derivatives. New drugs are thus urgently needed in case resistance to artemisinin-based compounds becomes more widespread and severe.

The project

The CUREMAL project is advancing a highly promising new antimalarial, GSK3772701, developed by GlaxoSmithKline (GSK). Like artemisinin derivatives, GSK3772701 is a potent, fast-acting P. falciparum whole-cell inhibitor with a novel mode of action and is active against both sensitive and multidrug-resistant parasites. Encouraging safety findings have been observed in phase I studies, and no parasites exhibiting reduced sensitivity to the compound have yet been detected.

The CUREMAL project is organising two sequential phase II trials in sub-Saharan Africa. The first will be a safety and pharmacokinetic study of GSK3772701 in Gabon and Uganda, using different doses and treatment durations in adults with uncomplicated malaria.

A follow-on trial will then assess the efficacy of the most promising treatment schedules when GSK3772701 is combined with pyronaridine. This study will involve children, adolescents and adults with malaria in Gabon, Tanzania and Uganda. This trial will begin in adults and then recruit younger age groups once safety and efficacy have been confirmed.

In addition, the project will genetically analyse malaria parasites from infections that are not cleared, screening for known resistance genes and sequencing parasite genomes to detect new variants associated with reduced drug susceptibility. Susceptibility testing studies will also be carried out to provide insights into the mechanisms of action of any resistance genes detected. 

Impact

The CUREMAL project will provide initial efficacy data on a highly promising new antimalarial. It will:

• Confirm the safety of GSK3772701 in African populations and provide the first efficacy data.
• Demonstrate whether treatment duration can be reduced from three days to two days.
• Provide critical data on the presence of antimalarial resistance genes, enhancing monitoring of the spread of resistance.

If early promising findings are confirmed, data from the CUREMAL project would support the development of a definitive phase III trial, which would generate the data needed for licensing and introduction of this much-needed new class of antimalarial drug.