None of three adults given the highest study dose of the experimental monoclonal antibody MAM01 before malaria infection had parasites in their bloodstream up to 26 weeks later, according to a phase 1 randomized controlled trial published in The Lancet Infectious Diseases.
“Although new vaccines are available, protective efficacy is not optimum,” the authors noted. “Monoclonal antibodies targeting the Plasmodium falciparum circumsporozoite [infectious] protein have potential to simplify prevention.”
Safe and well-tolerated
For the adaptive dose-escalation trial, researchers from the University of Maryland, the biotechnology company Sanaria, the Vital Narrative consultancy, and the Gates Medical Research Institute randomly assigned 37 malaria-naïve adults aged 18 to 50 years to receive a single dose of MAM01 or a placebo from August 2023 to December 2024.
Progress driving down the cost of goods coupled with dose selection within target populations will dictate the feasibility of malaria monoclonal antibody deployment.
Participants in the MAM01 and control groups were infected through the bites of five mosquitoes infected with the parasite Plasmodium falciparum NF54 18 to 26 weeks after administration of the monoclonal antibody or placebo. An untreated infectivity control patient was also enrolled to estimate efficacy.
The MAM01 doses were 1.5, 5, 10, and 40 milligrams per kilogram (mg/kg) intravenously or a subcutaneous dose of 5 mg/kg. A second, subcutaneous, dose of 5 mg/kg was administered to cohorts that received 5 mg/kg subcutaneously or intravenously 2 to 4 weeks post-infection.
After the investigators reviewed sentinel-group safety data (1.5 mg/kg) in one participant and placebo in another participant, 29 participants were assigned to receive MAM01, and 6 were assigned to receive placebo.
MAM01 administration was well tolerated, and no treatment-related serious adverse events occurred after one or two doses. After infection, 6 of 6 participants in the control group and 18 of 22 participants in the MAM01 group had malaria parasites in their blood, but none of three recipients of the 40 mg/kg intravenous–dose had parasites. Pharmacokinetic analysis showed that serum MAM01 concentrations greater than 88 micrograms per milliliter (μg/mL) protected against malaria.
“MAM01 was well tolerated, met safety targets, and showed clinical proof-of-principle by eliciting protection in malaria-naive adults using the controlled human malaria infection model,” the authors wrote. “Progress driving down the cost of goods coupled with dose selection within target populations will dictate the feasibility of malaria monoclonal antibody deployment.”
Prophylaxis in yearly rotation with other monoclonal antibodies
In a commentary in the same journal, Freia-Raphaella Lorenz, MD, of Radboud University Medical Centre in the Netherlands, and Matthew B.B. McCall, PhD, of the Centre de Recherches Medicales de Lambarene in Gabon, said a monoclonal antibody could prove a valuable treatment option by providing immediate, high-level protection over multiple months, a simplified dosing regimen, and consistent effectiveness, regardless of the recipient’s immunologic background.
“How MAM01 would best be integrated into the current landscape of active and passive immunisation strategies, as well as other interventions against malaria, remains to be resolved,” they wrote.
“One potential scenario might be seasonal prophylaxis in yearly rotation with other monoclonal antibodies to help prevent parasite escape mutants,” they added. “Implementation of monoclonal antibodies in general will depend in large part on developments in large-scale production costs, which this new addition to the armamentarium might help to drive down.”