- To discover and develop new treatments that are active against malaria parasites resistant to current treatments
- To discover and develop new treatments that could cure acute malaria with a single encounter treatment
- To discover and develop novel malaria compounds that target both liver stage and blood stage infections
What are the health needs and challenges?
Malaria is one of the most widespread infectious diseases, and claims the lives of an estimated 429,000 people a year, most of them in sub-Saharan Africa. A child dies of malaria every 2 minutes in Africa. Nearly half of the world’s population is at risk of contracting malaria. Children and pregnant women are among the most vulnerable. Drug resistance to most common antimalarials is increasing.
Two major malaria-causing organisms are Plasmodium falciparum and Plasmodium vivax.
Description of partnership activities and how they address needs and challenges
The Novartis Institute for Tropical Diseases (NITD) is collaborating with several partners, including the Genomics Institute of the Novartis Research Foundation the Swiss Tropical and Public Health Institute, and the Biomedical Primates Research Center (Netherlands) to discover new antimalarial compounds that target both Plasmodium falciparum and Plasmodium vivax. The discovery program is supported in part by the Wellcome Trust, the Singapore Economic Development Board and Medicines for Malaria Venture (MMV).The NITD and its partners are developing a potential one-dose cure for Plasmodium falciparum, and a curative modality for Plasmodium vivax. Two compounds resulting from these drug discovery efforts are currently in Phase II clinical trials: KAE609 and KAF156. These two compounds are from distinct chemical classes and target different malaria parasite pathways. . If successfully developed, they would be the first new antimalarials in many years not belonging to the artemisinin class, and provide completely new options to treat the disease
Summary of impact and forward looking information
KAE609 belongs to a new class called spiroindolones, the first true innovation since the launch of artemisinin-based combination therapies (ACTs). It kills the blood stages of Plasmodium falciparum and Plasmodium vivax through a novel mechanism of action, including parasites that have developed drug resistance. It also appears to be effective against the sexual forms of the parasite, so could also help prevent disease transmission. In 2012, KAE609 successfully achieved Proof of Concept (PoC) in a trial conducted in Asia, including a site in Thailand near the Myanmar border where resistance to current therapies has been reported.
We are developing KAF156 with scientific and financial support from Medicines for Malaria Venture (in collaboration with the Bill & Melinda Gates Foundation), exploring ways to combine it with another agent to achieve a new treatment option for malaria. KAF156, currently in Phase IIb clinical development, belongs to a novel class of antimalarial compounds called imidazolopiperazines, that act against both the blood and liver stages of the parasite's lifecycle. In September 2016, Novartis published proof of concept study results in the New England Journal of Medicine showing that KAF156 demonstrated activity against both vivax and falciparum malaria, including artemisinin-resistant parasites.
In addition, our scientists are working on other projects, targeting yet another novel mechanism against malaria.
Learn more about the Novartis Malaria R&D efforts