What are the health needs and challenges?

Malaria is one of the most widespread infectious diseases, with an estimated 249 million cases and 608,000 deaths in 2022. The greatest disease burden is in sub-Saharan Africa, where malaria is the leading cause of child mortality: a child dies of malaria in Africa every minute.

Despite substantial achievements in malaria control and elimination over the past two decades, the rise of drug resistance to artemisinin could jeopardize years of hard-won progress. This growing threat underscores the urgent need to develop new antimalarials.

Partnership activities and how they address needs and challenges

In 1999, Novartis launched Coartem^® (artemether-lumefantrine), the first fixed-dose artemisinin-based combination therapy (ACT) antimalarial, prequalified by the World Health Organization (WHO) for its efficacy, safety and quality. Artemether-lumefantrine is also listed on the WHO’s Model List of Essential Medicines.

In 2009, Novartis and Medicines for Malaria Venture (MMV) introduced Coartem^® Dispersible, the first ACT formulation specifically developed to address the needs of children with malaria. Although children are the most vulnerable to malaria, there was until then no quality treatment adapted for this patient group, and caregivers often had to crush bitter-tasting antimalarial tablets for children to swallow.

In 2024, Novartis and MMV completed a clinical study (phase II/III CALINA study) of a new dose and ratio of Coartem^® for babies weighing less than five kilograms, for whom there is no approved malaria treatment. The optimized dose of artemether-lumefantrine is designed to account for metabolic differences in these small babies. Data from the study have been submitted for regulatory review. If approved, Novartis and MMV aim to make the treatment available as soon as possible to these infants.

Today, resistance to artemisinin presents the biggest threat to the progress that has been made against malaria over the past 20 years. New medicines are therefore urgently needed to support countries working toward malaria control and elimination. Novartis has a robust research pipeline focused on delivering the next generation of antimalarials. This work is made possible through product development partnerships and close collaboration with academic, government, and philanthropic organizations.

Details of several new antimalarial compounds discovered at Novartis and currently in clinical trials include:

• Ganaplacide belongs to a novel class of antimalarial compounds that act against both the blood and liver stages of the parasite’s lifecycle. It has the potential to not only clear infection but also block the transmission of the malaria parasite. The compound demonstrated activity against both Plasmodium falciparum and Plasmodium vivax malaria, including artemisinin-resistant parasites. It also appears to be effective against the sexual forms of the parasite (gametocytes). It is being developed as a combination with a new formulation of lumefantrine, allowing the combination to be given once daily. The trial is conducted in collaboration with the WANECAM2 consortium funded by the European and Developing Countries Clinical Trial Partnership (EDCTP) across several sites in sub-Saharan Africa. Novartis leads the development of this compound with scientific and financial support from MMV in collaboration with the Bill & Melinda Gates Foundation.
• Cipargamin is another compound with a novel mechanism of action, which displays extremely rapid parasite clearance in patients. It is being developed as an intravenous infusion 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 was discovered through a joint research program involving Novartis Global Health research, 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 MMV. It is currently being evaluated in a phase 2 clinical study (KARISMA) in patients with severe malaria. The trial is conducted in collaboration with the PAMAfrica consortium funded by the European and Developing Countries Clinical Trial Partnership (EDCTP).
• INE963 is a fast acting long-lasting antimalarial with a high barrier to drug resistance. INE963 is under investigation in combination with other antimalarial agents as a single dose cure. It is being developed in collaboration with MMV and received the organization’s “Project of the Year” award in 2020.

Renewed commitment to malaria elimination

In June 2022, at the Kigali Summit on Malaria and Neglected Tropical Diseases (NTDs), Novartis announced a five-year (2021-2025) financial commitment of USD 250 million to advance R&D of new treatments to combat malaria and NTDs.