What are the health needs and challenges?

Malaria is one of the most widespread infectious diseases, with an estimated 247 million cases annually and claims the lives of an estimated 619,000 people a year, most of them in sub-Saharan Africa. A child dies of malaria every minute 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.

Partnership activities and how they address needs and challenges

Novartis is collaborating with several partners, including the Swiss Tropical and Public Health Institute, the Walter Reed Army Institute of Research, Mahidol University, Oregon Health & Science University and Malaria Drug Accelerator Consortium to discover new antimalarial compounds. The discovery program is supported in part by the Bill & Melinda Gates Foundation (BMGF) and Medicines for Malaria Venture (MMV).

KAF156 (ganaplacide) belongs to a novel class of antimalarial compounds that act against both the blood and liver stages of the parasite’s lifecycle. It demonstrated activity against both vivax and falciparum malaria, including artemisinin-resistant parasites. It is being developed as a combination with a new formulation of lumefantrine. This novel antimalarial combination will enter Phase 3 development in 2023. Novartis leads the development of this compound with scientific and financial support from MMV in collaboration with the Bill & Melinda Gates Foundation.

KAE609 (cipargamin) is another compound with a novel mechanism of action, which displays extremely rapid parasite clearance in patients. It is being developed for the treatment of severe malaria with financial support from Wellcome. It belongs to a new class called spiroindolones. It demonstrated rapid clearance of parasites pre-clinically and in patients, killing the blood stages of Plasmodium falciparum and Plasmodium vivax through a novel mechanism of action (PfATP4 inhibition), including parasites that have markers of drug resistance. It also appears to be effective against the sexual forms of the parasite (gametocytes), and therefore could also help prevent disease transmission. It was discovered through a joint research program with the Novartis Institute for Tropical Diseases, Novartis Natural Products Research Group, the Genomics Institute of the Novartis Research Foundation, and the Swiss Tropical and Public Health Institute. Research was supported by Wellcome, the Singapore Economic Development Board, and Medicines for Malaria Venture (MMV). Novartis leads the development of cipargamin with financial support from Wellcome.

In 2020, Novartis advanced another novel malaria therapy, INE963, a fast acting long-lasting antimalarial with an entirely new mechanism of action. It is developed in collaboration with MMV and received the organization’s “Project of the Year” award in 2020.

Malaria continues to strike hardest against pregnant women and children in Africa. Therefore, we are also developing a new optimized dose strength of our ACT to address the needs of infants weighing less than five kilograms. The clinical trial for this new treatment started in 2021 and is ongoing.

The clinical trials for ganaplacide are conducted as part of the WANECAM 2 consortium, while trials for cipargamin and our infant formulation are part of the PAMAfrica research consortium led by MMV. Both trials are funded by the European and Developing Countries Clinical Trials Partnership (EDCTP).