Subcutaneous REGEN-COV Antibody Combination in Early Asymptomatic SARS-CoV-2 Infection: A Randomized Clinical Trial

Abstract

Background: Casirivimab and imdevimab administered together (REGEN-COV) markedly reduces the risk of hospitalization or death in high-risk, symptomatic individuals with COVID-19. Here, we report phase 3 results of early treatment of asymptomatic, SARS-CoV-2-positive adults and adolescents with subcutaneous REGEN-COV. Methods: Individuals ≥12 years of age were eligible if identified within 96 hours of a household contact being diagnosed as SARS-CoV-2-positive; 314 were randomized 1:1 to receive subcutaneous REGEN-COV 1200mg or placebo. The primary endpoint was the proportion of infected participants without evidence of prior immunity (i.e., SARS-CoV-2-RT-qPCR-positive/seronegative) who subsequently developed symptomatic Covid-19 during a 28-day efficacy assessment period. Results: Subcutaneous REGEN-COV 1200mg significantly prevented progression from asymptomatic to symptomatic disease compared with placebo (31.5% relative risk reduction; 29/100 [29.0%] vs. 44/104 [42.3%], respectively; P=0.0380). REGEN-COV also reduced the overall population burden of high viral load weeks (39.7% reduction vs. placebo; 48 vs. 82 total weeks; P=0.0010) and of symptomatic weeks (45.3% reduction vs. placebo; 89.6 vs. 170.3 total weeks; P=0.0273), the latter corresponding to an approximately 5.6-day reduction per symptomatic participant. Six placebo-treated participants had a Covid-19-related hospitalization or ER visit versus none for those receiving REGEN-COV. The proportion of participants receiving placebo who had ≥1 treatment-emergent adverse events was 48.1% compared to 33.5% for those receiving REGEN-COV, including Covid-19-related (39.7% vs. 25.8%, respectively) or non-Covid-19-related (16.0% vs. 11.0%, respectively) events. Conclusions: Subcutaneous REGEN-COV 1200mg prevented progression from asymptomatic to symptomatic infection, reduced the duration of high viral load and symptoms, and was well tolerated.

Antibody and cellular therapies for treatment of covid-19: a living systematic review and network meta-analysis

“…After screening 52350 titles and abstracts and 1029 full texts, 47 unique randomised controlled trials that evaluated antiviral antibody or cellular treatments were identified as of 21 July 2021 (fig 1). 43444546474849505152535455565758596061626364656667686970717273747576777879808182838485868788 A table of excluded full texts is provided in the supplementary data on bmj.com. Searches of living evidence retrieval services identified 11 publications of eligible randomised trials, which were reconciled with our formal search strategy when necessary 222324254549566466676875838688.…”

Casirivimab/Imdevimab: First Approval

“…An ongoing randomized, double-blind, placebo-controlled, phase 3 trial (NCT04452318) is assessing the efficacy of subcutaneous casirivimab/imdevimab in preventing SARS-CoV-2 infection and subsequent symptomatic COVID-19 in uninfected household contacts of infected individuals (part A) and preventing symptomatic COVID-19 in household contacts recently infected with SARS-CoV-2 but asymptomatic (part B) [ 9 , 20 , 21 ]. The trial enrolled individuals aged ≥ 12 years living with a SARS-CoV-2-infected patient.…”

“…In cohort B, early treatment with casirivimab/imdevimab was effective in preventing asymptomatic SARS-CoV-2 infection from progressing to symptomatic COVID-19 [ 20 ]. Of the 314 subjects randomized in this cohort, 207 were seronegative at baseline and 204 of these were assessed for efficacy (three seronegative subjects were determined post-randomization to be symptomatic at baseline and excluded).…”

“…Of the 314 subjects randomized in this cohort, 207 were seronegative at baseline and 204 of these were assessed for efficacy (three seronegative subjects were determined post-randomization to be symptomatic at baseline and excluded). Signs or symptoms of COVID-19 developed within 14 days of a baseline positive RT-qPCR test or during the 28-day efficacy assessment period in 29.0% of casirivimab/imdevimab recipients ( n = 100) versus 42.3% of placebo recipients ( n = 104) in this population, representing a 31.5% relative risk reduction (OR 0.54; 95% CI 0.30–0.97; p = 0.0380) [primary endpoint] [ 20 ]. The mean duration of symptoms per symptomatic patient was 21.7 and 27.3 days in the respective groups.…”

“…Mean viral load appeared to decline more rapidly with casirivimab/imdevimab than with placebo, with an adjusted mean difference of − 1.5 log 10 copies/mL at day 8; the mean number of days with high viral load (> 4 log 10 copies/mL) was 3.4 versus 5.7. No casirivimab/imdevimab recipients had a COVID-19-related hospitalization or emergency room visit compared with six placebo recipients [ 20 ].…”