A subcutaneous combination therapy (REGEN-COV, Regeneron Pharmaceuticals) consisting of 2 neutralizing human sequence neutralizing monoclonal antibodies, i.e. subcutaneous casirivimab and imdevimab, reduced the incidence of symptomatic COVID-19 among newly exposed asymptomatic individuals, according to the authors of a multicenter study. Meagan P. O’Brien, MD, of Regeneron Pharmaceuticals, and lead author of the study, reported the results of the COVID-19 Phase 3 Prevention Trial Team in JAMA.1
The investigators performed a randomized, double-blind, placebo-controlled, phase 3 clinical trial to determine the effectiveness of this therapy in preventing symptomatic COVID-19 in those who were recently infected and asymptomatic.
Participants in this study were close household contacts with patients with SARS-CoV-2 from 112 locations in the United States, Romania, and Moldova. The investigation period ranged from 13 July 2020 to 28 January 2021; participants who were eligible for study inclusion if identified within 96 hours of a positive test result from an index case were followed until March 11, 2021.
The asymptomatic subjects were randomized to receive either 1 dose of subcutaneous casirivimab / imdevimab (1,200 mg in total; 600 mg of each; n = 158) or placebo (n = 156). The primary endpoint was the proportion of seronegative participants who developed symptomatic COVID-19 during the 28-day efficacy assessment period; the secondary endpoints were the number of weeks with symptomatic SARS-CoV-2 infection and the number of weeks with high viral load (> 4 log10 copies / ml), the authors reported.
Subcutaneous antibody effect
Analysis showed a significant difference in the 2 study groups. Of the 314 asymptomatic patients randomized, 310 completed the assessment and 204 were asymptomatic and seronegative at baseline and included in the primary efficacy analysis. Of these, 100 had been randomized to active treatment and 104 to placebo. The results showed that progression to symptomatic disease developed in 29% and 42.3%, respectively, a difference that reached significance (p = 0.04).
The active treatment also achieved approx. 5.6 days decrease in symptom duration in the symptomatic participant and reduced the number of weeks with high viral load compared to placebo. Active treatment also caused fewer side effects compared to placebo.
The investigators concluded: “Among asymptomatic SARS-CoV-2 RT-qPCR-positive subjects living with an infected household contact, treatment with subcutaneous casirivimab and imdevimab antibody combination versus placebo significantly reduced the incidence of symptomatic COVID-19 over 28 days.”
O’Brien MP, Forleo-Neto E, Sarkar N, et al. for the COVID-19 Phase 3 Prevention Experiment Team. Effect of subcutaneous Casirivimab and Imdevimab antibody combination vs placebo on the development of symptomatic COVID-19 in early asymptomatic SARS-CoV-2 infection: a randomized clinical trial. JAMA 2022; 327 (5): 432-441. doi: 10.1001 / jama.2021.24939