The following is a summary of “Safety, Tolerability and Pharmacokinetics of Half-Life Extended Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Monoclonal Antibodies AZD7442 (Tixagevimab-Cilgavimab) in Healthy Adults,” published in the May 2023 issue of Infectious Diseases by Soto, et al.

The combination of tixagevimab and cilgavimab, known as AZD7442, consists of extended half-life, SARS-CoV-2-specific neutralizing monoclonal antibodies. However, the effectiveness of AZD7442 in preventing COVID-19 and its long-term safety profile has yet to be fully evaluated.

In the phase 1 study, conducted from August to October 2020, healthy adults aged 18-55 were randomly assigned to receive intramuscular (300 mg) or intravenous (300, 1,000, or 3,000 mg) doses of AZD7442 or a placebo. The primary objective was to assess the safety and tolerability of AZD7442, while secondary objectives included evaluating its pharmacokinetics and monitoring the development of anti-drug antibodies.

A total of 60 participants were enrolled in the study, with 50 receiving AZD7442 and 10 receiving the placebo. Adverse events, mostly mild or moderate in intensity, occurred in 26 participants (52.0%) in the AZD7442 groups and 8 participants (80.0%) in the placebo group. No infusion or injection site reactions or hypersensitivity reactions were reported. The mean half-lives of tixagevimab and cilgavimab were approximately 90 days, and their pharmacokinetic profiles remained consistent over the 361-day study period. AZD7442 maintained SARS-CoV-2-specific neutralizing antibody titers above those found in plasma from convalescent COVID-19 patients.

AZD7442 demonstrated favorable safety and tolerability profiles in healthy adults across all administered doses. Based on pharmacokinetic analyses, a single intramuscular dose of 300 mg of AZD7442 may offer protection against symptomatic COVID-19 for at least six months, depending on the SARS-CoV-2 variant. However, further research was needed to fully assess the efficacy and long-term effects of AZD7442 in preventing COVID-19.

Source: academic.oup.com/jid/article/227/10/1153/6997870