Novartis and the Medicines for Malaria Venture (MMV) have announced the advancement of a novel drug combination into Phase 3 clinical trials, offering renewed hope in the fight against rising artemisinin-resistant malaria. The combination therapy, pairing ganaplacide with a new solid dispersion formulation (SDF) of lumefantrine, presents a non-artemisinin-based approach to treating uncomplicated Plasmodium falciparum malaria.
The SDF formulation allows for a simplified once-daily dosing regimen, which Novartis and MMV believe could improve patient adherence and treatment outcomes. The therapy has shown potential not only to clear malaria infections, including those resistant to artemisinin, but also to block the transmission of the malaria parasite.
Promising Phase 2 Results
Last year, Novartis and MMV reported findings from a Phase 2 open-label study involving 524 adults and children with acute uncomplicated malaria. The results indicated that the ganaplacide/lumefantrine combination was as effective as Coartem (artemether-lumefantrine), a widely used artemisinin-based combination therapy (ACT) pioneered by Novartis. Coartem has been a cornerstone of malaria treatment since its introduction in 1999, with over a billion doses provided by Novartis, largely on a not-for-profit basis.
The Threat of Artemisinin Resistance
However, the increasing prevalence of artemisinin resistance, particularly in the Greater Mekong region of Southeast Asia and, more recently, in East African countries like Rwanda and Uganda, poses a significant threat to global malaria control efforts. A 2022 study by the Global Fund warned that drug resistance in the Greater Mekong region "now threatens a devastating setback for the region and a major shock to health security if it goes global."
Phase 3 Trial Design
The upcoming Phase 3 trial will be conducted across multiple clinical sites in Burkina Faso, Mali, Gabon, and Niger, as well as other locations in sub-Saharan Africa. The study will compare the efficacy of ganaplacide/lumefantrine with that of artemether/lumefantrine, the current standard of care.
Addressing Unmet Needs
"The emergence of artemisinin resistance demands urgent action to develop new antimalarials," said Dr. Sujata Vaidyanathan, head of Novartis' global health development unit. "We need non-artemisinin-based medicines with novel mechanisms of action against resistant parasites, and simple, easy-to-follow dosing schedules to help increase treatment adherence."
Dr. Vaidyanathan emphasized the importance of rapidly developing and adopting new compounds to combat resistance: "The earlier we have new compounds and the faster the world adopts them, the better chance we stand of beating resistance."
Ganaplacide/lumefantrine has received fast track and orphan drug status from the FDA, highlighting the urgent need for new treatment options in the face of growing drug resistance.
