Monthly treatment with subcutaneous casirivimab/imdevimab was well tolerated and associated with significant protection against COVID-19 infection, according to results of a phase 1, double-blinded, placebo-controlled trial published in the International Journal of Infectious Diseases.
In this study, researchers assessed the safety, tolerability, and efficacy of monthly subcutaneous injections of casirivimab/imdevimab for the prevention of COVID-19 infection among uninfected adults (age range, 18-90 years). Patients were randomly assigned in a 3:1 fashion to receive either subcutaneous casirivimab/imdevimab (1200 mg) or placebo every 4 weeks for up to 24 weeks. The primary endpoints included the incidence of adverse events (AEs) of special interest within 4 days of treatment administration, and serum concentrations of casirivimab/imdevimab over time. The rate of treatment-emergent AEs and immunogenicity among the study population were assessed as secondary endpoints, with immunogenicity determined via measurement of anti-drug antibodies (ADAs) against casirivimab/imdevimab.
There were 969 patients included in the study, of whom 729 received casirivimab/imdevimab and 240 received placebo. Of all patients, the mean age was 48 years, 44.9% were women, 10% were Black, and 23.4% were Hispanic.
The incidence of COVID-19 infection during the study period was decreased among patients in the intervention vs placebo groups (0.4% vs 5.4%; odds ratio, 0.07; 95% CI, 0.01-0.27; nominal P <.001), indicating casirivimab/imdevimab was associated with a relative risk reduction of 92.4%.
Among 3 (0.4%) patients in the casirivimab/imdevimab group who reported COVID-19 infection as an AE, all were seronegative for SARS-CoV-2 antibodies at baseline and at the end of treatment and none had laboratory-confirmed COVID-19 infection.
No AEs of special interest or deaths were reported during the 6-month treatment period, and the rate of severe treatment-related AEs was similar between patients in the casiribimab/imdevimab group vs those in the placebo group (0.7% vs 0.8%). Injection site reactions occurred among 266 (36.5%) and 40 (16.7%) patients in the casirivimab/imdevimab and placebo groups, respectively. All injection site reactions were of mild or moderate severity, with the majority (>60%) resolving within 4 days of treatment administration.
Both casirivimab and imdevimab were associated with low treatment-emergent immunogenicity, with ADAs measured in 5% or less of the study population.
This study was limited by the lack of regular reverse transcription polymerase chain reacting testing among patients who developed symptoms suggestive of COVID-19 infection. In addition, the researchers were unable to assess the effect of nonpharmaceutical interventions on COVID-19 transmission, such as the use of personal protective equipment and social distancing.
According to the researchers, “…the efficacy and safety profile of [casirivimab/imdevimab] demonstrated in this study strongly support that [it] could be used for COVID-19 prophylaxis in individuals not expected to mount a sufficient immune response to vaccination when circulating variants are susceptible to [casirivimab/imdevimab].”
Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Isa F, Forleo-Neto E, Meyer J, et al. Repeat subcutaneous administration of casirivimab and imdevimab in adults is well-tolerated and prevents the occurrence of COVID-19. Int J Infect Dis. Published online July 1, 2022. doi:10.1016/j.ijid.2022.06.045