As the threat of resistance to current malaria treatments grows, Novartis and Medicines for Malaria Venture (MMV) announce the decision to progress ganaplacide/lumefantrine- solid dispersion formulation (SDF) into Phase 3 development for the treatment of patients with acute uncomplicated malaria due to Plasmodium falciparum.
Key highlights:
- Novartis and Medicines for Malaria Venture (MMV) announce decision to move to Phase 3 study for novel non-artemisinin combination to treat uncomplicated malaria.
- This combination also contains an optimised formulation of lumefantrine, which allows it to be given once daily versus the usual twice-daily administration, following the results from Phase 2.
- One large Phase 3 pivotal trial will compare the efficacy of ganaplacide/lumefantrine-SDF to the current ‘gold standard’ artemether-lumefantrine, planned to start in 2023.
Ganaplacide is a novel agent with a new mechanism of action, which is combined with a new formulation of lumefantrine optimised for once-daily dosing. This combination has the potential not only to clear malaria infection, including artemisinin-resistant strains, but also to block the transmission of the malaria parasite. The medicine is being developed with scientific and financial support from MMV and their partners.
As previously announced, a Phase 2 open-label, randomised controlled study was conducted in 524 adults and children with acute uncomplicated malaria due to Plasmodium falciparum infection. The ganaplacide/lumefantrine-SDF combination met the primary objective in both adults and children. In patients who received a once-daily dose of ganaplacide/lumefantrine-SDF during 3 days, response to treatment was similar to the rate observed in patients who received twice-daily artemether-lumefantrine control therapy during 3 days.
Planned to start in 2023, one large Phase 3 pivotal trial will compare the efficacy of ganaplacide/lumefantrine-SDF to the current ‘gold standard’ artemether-lumefantrine. The trial will be conducted in collaboration with the WANECAM 2 consortium, and will include partner clinical sites in Burkina Faso, Mali, Gabon and Niger as well as other sites in sub-Saharan Africa. Both Phase 2 and 3 studies receive funding from the European and Developing Countries Clinical Trials Partnership (EDCTP), which is supported by the European Union.
“The emergence of artemisinin resistance demands urgent action to develop new antimalarials. 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. The earlier we have new compounds and the faster the world adopts them, the better chance we stand of beating resistance,” said Dr. Sujata Vaidyanathan, head Global Health Development Unit, Novartis.
“We are increasingly seeing parasites with decreased sensitivity to artemisinin, even in Africa,” said Dr. Timothy Wells, chief scientific officer, MMV. “If the Phase 3 trial is successful, this new combination will increase the number of options available to countries and help save the lives of children at risk of this devastating disease.”
In August 2022, the US Food and Drug Administration (FDA) granted Fast Track Designation and Orphan Drug Designation for the combination of ganaplacide and lumefantrine-SDF for the treatment of acute, uncomplicated malaria.
Plasmodium falciparum malaria is primarily treated with artemisinin-based combination therapies (ACTs) such as artemether-lumefantrine. ACTs are still highly effective and well tolerated. Novartis introduced the first fixed-dose combination ACT in 1999 and has since delivered more than 1 billion courses of antimalarial treatment, largely at no profit.
Together with MMV, Novartis developed a taste-masked dispersible formulation of Coartem for children, which has now been used to treat more than 450 million children, mainly in Africa. However, the increased frequency by which parasites with a slower response to artemisinin are observed in some parts of Eastern Africa (Rwanda, Uganda, and the Horn of Africa) points to an urgent need to develop a new non-artemisinin class of antimalarials to avoid a return to the high levels of childhood mortality last seen in the 1990s.