Monoclonal Antibody L9LS and Malaria Prevention

Researchers have found that a single subcutaneous injection of an investigational monoclonal antibody called L9LS significantly reduces the risk of malaria in children. This phase II trial in Mali demonstrated that the antibody was both safe and effective in preventing Plasmodium falciparum infections among children aged 6 to 10 years. This study was published in The New England Journal Of Medicine by Kayentao and colleagues.

Malaria, a life-threatening disease caused by Plasmodium parasites, continues to pose a significant health burden worldwide, particularly in sub-Saharan Africa. In 2022, the World Health Organization (WHO) reported over 600,000 deaths due to malaria, the majority among young children. The development of long-acting drugs for malaria prevention could be a major step forward in controlling the disease.

The Mali Malaria mAB trial included 225 children aged 6 to 10 years and evaluated the safety and efficacy of L9LS in preventing malaria. Children were randomized to receive either a 150-mg dose, a 300-mg dose, or a placebo injection. Before the trial, participants were treated with antimalarial medication to clear any existing infections.

Key Findings of the Study

• Infection rates were significantly lower in both L9LS dose groups compared to the placebo group.
• Specifically, 48% of children in the 150-mg dose group and 40% in the 300-mg dose group became infected, compared to 81% in the placebo group.
• The antibody provided 67% efficacy with the 150-mg dose and 77% efficacy with the 300-mg dose against clinical malaria, compared to the placebo group.
• No safety concerns were identified in either phase of the study.
• Adverse events were rare, mild to moderate in severity, and resolved without intervention.

The study indicates that the L9LS monoclonal antibody offers substantial protection against malaria, providing a potentially transformative approach to malaria prevention in high-risk populations. The long-acting nature of the antibody, with its single-dose delivery, could enhance accessibility and adherence.

The trial's findings support the use of L9LS as a promising new tool in the fight against malaria. The antibody demonstrated a high level of efficacy and safety in preventing Plasmodium falciparum infection in children. As the global malaria community seeks new strategies to combat the disease, monoclonal antibodies like L9LS may play a critical role in achieving malaria eradication.

Reference

Kayentao, K., Ongoiba, A., Preston, A. C., Healy, S. A., Hu, Z., Skinner, J., Doumbo, S., Wang, J., Cisse, H., Doumtabe, D., Traore, A., Traore, H., Djiguiba, A., Li, S., Peterson, M. E., Telscher, S., Idris, A. H., Adams, W. C., McDermott, A. B., … Crompton, P. D. (2024). Subcutaneous administration of a monoclonal antibody to prevent malaria. The New England Journal of Medicine, 390(17), 1549–1559. https://doi.org/10.1056/nejmoa2312775