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Randomized Controlled Trial

Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19

Meagan P O'Brien et al. N Engl J Med. .

Abstract

Background: REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19). Whether subcutaneous REGEN-COV prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent Covid-19 in persons at high risk for infection because of household exposure to a person with SARS-CoV-2 infection is unknown.

Methods: We randomly assigned, in a 1:1 ratio, participants (≥12 years of age) who were enrolled within 96 hours after a household contact received a diagnosis of SARS-CoV-2 infection to receive a total dose of 1200 mg of REGEN-COV or matching placebo administered by means of subcutaneous injection. At the time of randomization, participants were stratified according to the results of the local diagnostic assay for SARS-CoV-2 and according to age. The primary efficacy end point was the development of symptomatic SARS-CoV-2 infection through day 28 in participants who did not have SARS-CoV-2 infection (as measured by reverse-transcriptase-quantitative polymerase-chain-reaction assay) or previous immunity (seronegativity).

Results: Symptomatic SARS-CoV-2 infection developed in 11 of 753 participants in the REGEN-COV group (1.5%) and in 59 of 752 participants in the placebo group (7.8%) (relative risk reduction [1 minus the relative risk], 81.4%; P<0.001). In weeks 2 to 4, a total of 2 of 753 participants in the REGEN-COV group (0.3%) and 27 of 752 participants in the placebo group (3.6%) had symptomatic SARS-CoV-2 infection (relative risk reduction, 92.6%). REGEN-COV also prevented symptomatic and asymptomatic infections overall (relative risk reduction, 66.4%). Among symptomatic infected participants, the median time to resolution of symptoms was 2 weeks shorter with REGEN-COV than with placebo (1.2 weeks and 3.2 weeks, respectively), and the duration of a high viral load (>104 copies per milliliter) was shorter (0.4 weeks and 1.3 weeks, respectively). No dose-limiting toxic effects of REGEN-COV were noted.

Conclusions: Subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. Among the participants who became infected, REGEN-COV reduced the duration of symptomatic disease and the duration of a high viral load. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04452318.).

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Figures

Figure 1
Figure 1. SARS-CoV-2 Infection in the REGEN-COV and Placebo Groups.
Panel A shows the cumulative incidence of symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after administration of REGEN-COV or placebo during the 28-day efficacy assessment period. The relative risk reduction was calculated as 1 minus the relative risk. The inset shows the same data on an enlarged y axis. The P value is based on a logistic-regression model including the fixed category effects of trial group (REGEN-COV or placebo), region (United States or other country), and participant age (12 to 49 years or ≥50 years). Panel B shows the aggregate total weeks of symptomatic SARS-CoV-2 infection in each trial group. In Panels B, D, and F, the calculation of the relative difference is based on the normalized weeks per 1000 participants, and the P value is based on a stratified Wilcoxon rank-sum test (van Elteren test) with region (United States or other country) and age group (12 to 49 years or ≥50 years) as strata. Panel C shows the mean duration of symptoms. Panel D shows the aggregate total weeks of any asymptomatic or symptomatic SARS-CoV-2 infection in each trial group. Panel E shows the mean duration of overall infection. Panel F shows the aggregate total weeks of a high SARS-CoV-2 viral load (>104 copies per milliliter) in each trial group. Panel G shows the mean duration of a high SARS-CoV-2 viral load. In Panels F and G, if viral-load data were missing at a visit, that visit was not included in the analysis, and only participants with at least one nasopharyngeal swab sample to detect the viral load after baseline were included. CI denotes confidence interval.
Figure 2
Figure 2. Viral Load in Participants with Asymptomatic and Symptomatic Infection.
Panel A shows the peak viral load according to symptom status. Data points represent individual participants. Panel B shows the viral load at the first positive reverse-transcriptase–quantitative polymerase-chain-reaction (RT-qPCR) test in all participants. Panel C shows the viral load at the first positive RT-qPCR test in all infected participants, according to symptom status. The boxes represent interquartile ranges, with the horizontal line in each box representing the median and the whiskers showing the values that were 1.5 times the values represented at each end of the box. The large diamonds in the boxes represent the mean.
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Update of

  • Subcutaneous REGEN-COV Antibody Combination for Covid-19 Prevention.
    O'Brien MP, Forleo-Neto E, Musser BJ, Isa F, Chan KC, Sarkar N, Bar KJ, Barnabas RV, Barouch DH, Cohen MS, Hurt CB, Burwen DR, Marovich MA, Hou P, Heirman I, Davis JD, Turner KC, Ramesh D, Mahmood A, Hooper AT, Hamilton JD, Kim Y, Purcell LA, Baum A, Kyratsous CA, Krainson J, Perez-Perez R, Mohseni R, Kowal B, DiCioccio AT, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD, Weinreich DM. O'Brien MP, et al. medRxiv [Preprint]. 2021 Jun 17:2021.06.14.21258567. doi: 10.1101/2021.06.14.21258567. medRxiv. 2021. Update in: N Engl J Med. 2021 Sep 23;385(13):1184-1195. doi: 10.1056/NEJMoa2109682. PMID: 34159344 Free PMC article. Updated. Preprint.

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