Subcutaneous REGEN-COV Antibody Combination for Covid-19 Prevention

Abstract

Background: Casirivimab and imdevimab (REGEN-COV™) markedly reduces risk of hospitalization or death in high-risk individuals with Covid-19. Here we explore the possibility that subcutaneous REGEN-COV prevents SARS-CoV-2 infection and subsequent Covid-19 in individuals at high risk of contracting SARS-CoV-2 by close exposure in a household with a documented SARS-CoV-2-infected individual.

Methods: Individuals ≥12 years were enrolled within 96 hours of a household contact being diagnosed with SARS-CoV-2 and randomized 1:1 to receive 1200 mg REGEN-COV or placebo via subcutaneous injection. The primary efficacy endpoint was the proportion of participants without evidence of infection (SARS-CoV-2 RT-qPCR-negative) or prior immunity (seronegative) who subsequently developed symptomatic SARS-CoV-2 infection during a 28-day efficacy assessment period.

Results: Subcutaneous REGEN-COV significantly prevented symptomatic SARS-CoV-2 infection compared with placebo (81.4% risk reduction; 11/753 [1.5%] vs. 59/752 [7.8%], respectively; P<0.0001), with 92.6% risk reduction after the first week (2/753 [0.3%] vs. 27/752 [3.6%], respectively). REGEN-COV also prevented overall infections, either symptomatic or asymptomatic (66.4% risk reduction). Among infected participants, the median time to resolution of symptoms was 2 weeks shorter with REGEN-COV vs. placebo (1.2 vs. 3.2 weeks, respectively), and the duration of time with high viral load (>10⁴ copies/mL) was lower (0.4 vs. 1.3 weeks, respectively). REGEN-COV was generally well tolerated.

Conclusions: Administration of subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in uninfected household contacts of infected individuals. Among individuals who became infected, REGEN-COV reduced the duration of symptomatic disease, decreased maximal viral load, and reduced the duration of detectable virus.(ClinicalTrials.gov number, NCT04452318.).

Figure 1.. REGEN-COV Reduces Symptomatic Infection in Those Who Are Uninfected at Baseline.

Panel A shows cumulative incidence of symptomatic infection following administration of REGEN-COV or placebo. Panel B shows combined total weeks of symptomatic SARS-CoV-2 infection in each treatment group. Panel C shows duration of symptoms per symptomatic infected participant. Panel D shows combined total weeks of any SARS-CoV-2 infection in each treatment group. Panel E shows duration of overall infection per any infected participant. Panel F shows combined total weeks of high SARS-CoV-2 viral load (>10⁴ copies/ml) in each treatment group. Panel G shows duration of high SARS-CoV-2 viral load (>10⁴ copies/ml) per infected participant. *Based on a logistic regression model including fixed category effects of treatment group (placebo vs. REGEN-COV), region (US vs. ex-US), and age (≥12 to <50 years of age, ≥50 years of age). †Based on the normalized weeks per 1000 participants.

ǂBased on a stratified Wilcoxon rank sum test (van Elteren test) with region (US vs. ex-US) and age group (12 to <50 years of age vs. ≥50 years of age) as strata. §If a visit had missing viral load data, that visit was not included in the analysis. Only participants with at least one post-baseline viral load nasopharyngeal swab samples were included in this analysis. CI denotes confidence interval, SARS-CoV-2 severe acute respiratory syndrome coronavirus 2, SC subcutaneous, and SD standard deviation.

Figure 1.. REGEN-COV Reduces Symptomatic Infection in Those Who Are Uninfected at Baseline.

Panel A shows cumulative incidence of symptomatic infection following administration of REGEN-COV or placebo. Panel B shows combined total weeks of symptomatic SARS-CoV-2 infection in each treatment group. Panel C shows duration of symptoms per symptomatic infected participant. Panel D shows combined total weeks of any SARS-CoV-2 infection in each treatment group. Panel E shows duration of overall infection per any infected participant. Panel F shows combined total weeks of high SARS-CoV-2 viral load (>10⁴ copies/ml) in each treatment group. Panel G shows duration of high SARS-CoV-2 viral load (>10⁴ copies/ml) per infected participant. *Based on a logistic regression model including fixed category effects of treatment group (placebo vs. REGEN-COV), region (US vs. ex-US), and age (≥12 to <50 years of age, ≥50 years of age). †Based on the normalized weeks per 1000 participants.

ǂBased on a stratified Wilcoxon rank sum test (van Elteren test) with region (US vs. ex-US) and age group (12 to <50 years of age vs. ≥50 years of age) as strata. §If a visit had missing viral load data, that visit was not included in the analysis. Only participants with at least one post-baseline viral load nasopharyngeal swab samples were included in this analysis. CI denotes confidence interval, SARS-CoV-2 severe acute respiratory syndrome coronavirus 2, SC subcutaneous, and SD standard deviation.

Figure 1.. REGEN-COV Reduces Symptomatic Infection in Those Who Are Uninfected at Baseline.

Panel A shows cumulative incidence of symptomatic infection following administration of REGEN-COV or placebo. Panel B shows combined total weeks of symptomatic SARS-CoV-2 infection in each treatment group. Panel C shows duration of symptoms per symptomatic infected participant. Panel D shows combined total weeks of any SARS-CoV-2 infection in each treatment group. Panel E shows duration of overall infection per any infected participant. Panel F shows combined total weeks of high SARS-CoV-2 viral load (>10⁴ copies/ml) in each treatment group. Panel G shows duration of high SARS-CoV-2 viral load (>10⁴ copies/ml) per infected participant. *Based on a logistic regression model including fixed category effects of treatment group (placebo vs. REGEN-COV), region (US vs. ex-US), and age (≥12 to <50 years of age, ≥50 years of age). †Based on the normalized weeks per 1000 participants.

ǂBased on a stratified Wilcoxon rank sum test (van Elteren test) with region (US vs. ex-US) and age group (12 to <50 years of age vs. ≥50 years of age) as strata. §If a visit had missing viral load data, that visit was not included in the analysis. Only participants with at least one post-baseline viral load nasopharyngeal swab samples were included in this analysis. CI denotes confidence interval, SARS-CoV-2 severe acute respiratory syndrome coronavirus 2, SC subcutaneous, and SD standard deviation.

Figure 2.. Individuals Who Become Infected Despite REGEN-COV Treatment Demonstrate Lower Viral Burden Compared With Placebo-Treated Individuals.

Panel A shows peak viral load by symptomatic infection status. Panel B shows all infected participants: viral load at first positive RT-qPCR. Panel C shows infected participants by symptoms: viral load at first positive RT-qPCR. Lines in the boxes represent the median. Large, bolded dots in the boxes represent the mean. Bottom and top of boxes represent quartiles 1 (25th percentile) and 3 (75th percentile), respectively. Whiskers represent the 1.5 times interquartile range. RT-qPCR denotes quantitative real-time polymerase chain reaction, and SC subcutaneous.

Figure 2.. Individuals Who Become Infected Despite REGEN-COV Treatment Demonstrate Lower Viral Burden Compared With Placebo-Treated Individuals.

Panel A shows peak viral load by symptomatic infection status. Panel B shows all infected participants: viral load at first positive RT-qPCR. Panel C shows infected participants by symptoms: viral load at first positive RT-qPCR. Lines in the boxes represent the median. Large, bolded dots in the boxes represent the mean. Bottom and top of boxes represent quartiles 1 (25th percentile) and 3 (75th percentile), respectively. Whiskers represent the 1.5 times interquartile range. RT-qPCR denotes quantitative real-time polymerase chain reaction, and SC subcutaneous.