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14th November 2022
The malarial monoclonal antibody CIS43LS has shown a high level of efficacy after 6 months against plasmodium falciparum during the malaria season in Mali according to the findings of a study by researchers from the Mali Malaria mAb trial team.
Malaria is caused by four members of the plasmodium species including Plasmodium falciparum, P. vivax, P. ovale, and P. malariae and is transmitted after being bitten by an infective female Anopheles mosquito producing a febrile illness. Malaria is an extremely common infection and which, according to the World Health Organization (WHO), led to 241 million cases in 2020 (up from 227 million in 2019) and an estimated 627 000 deaths. The infection disproportionately affects individuals on the African continent and WHO estimates that in 2020, 95% of all malaria cases and 96% of deaths occurred within the region with children under 5 years of age accounting for about 80% of all malaria deaths. A study published in 2015 found that a candidate malaria vaccine prevented a substantial number of cases of clinical malaria over a 3–4-year period in young infants and children when administered with or without a booster dose. As well as vaccines, a malarial monoclonal antibody, CIS43LS has been developed and which targets the circumsporozoite protein which covers the surface of the infecting sporozoites and has a critical role in sporozoite development in the mosquito, and invasion of hepatocytes necessary for initiation of malaria infection. CIS43LS binds with the circumsporozoite protein, inhibiting its action and is therefore highly effective for passive prevention of malaria. In a phase 1 trial, administration of CIS43LS to adults who had never had malaria infection or vaccination, prevented malaria after controlled infection.
Based on these early and positive findings, researchers undertook a phase 2 trial to assess the efficacy and safety of CIS43LS in healthy adults in Mali during a 6-month malaria season. After an initial dose ranging study, individuals were randomised 1:1:1 to receive CIS43LS doses of either 10 mg/kg/bodyweight, 40 mg or placebo. The primary efficacy endpoint was the first detection of P. falciparum infection in blood smear examination, and which was checked every 2 weeks for a total of 24 weeks. Prior to the study, all participants were given artemether–lumefantrine for treatment of any existing malarial infection.
Malarial monoclonal antibody efficacy
A total of 330 individuals with a median age of 34.6 years (43% female) were equally randomised to either 10, 40 mg/kg dose of CIS43LS or placebo. At enrolment, plasmodium infection was still present in 12.7% of those receiving 10 mg, 7.3% in the 40 mg group and a similar proportion of placebo participants.
The primary efficacy, i.e., P. falciparum infection, was seen in 35.5% of those receiving 10 mg, 18.2% in the 40 mg group but in 78.2% of placebo participants. At 6 months the efficacy of the 40 mg/kg dose (compared to placebo) was 88.2% and 75% for the 10 mg dose and both comparisons were statistically significant.
In terms of safety, the risk of a moderate headache was 3.3 times as high with the 40 mg/kg dose compared to placebo.
The authors concluded that CIS43LS was effective over a 6-month malaria season and without any evidence of safety concerns.
Kayentoa K et al. Safety and Efficacy of a Monoclonal Antibody against Malaria in Mali. N Engl J Med 2022