ABSTRACT
Background:A previous report showed that a single 1200 mg subcutaneous (SC) dose of casirivimab and imdevimab (cas/imd) prevented symptomatic COVID-19 by 81.4% and reduced all SARS-CoV-2 infections (symptomatic and asymptomatic) by 66.4% in household contacts living with recently infected individuals over a 28-day period. While highly effective vaccines now exist for the prevention of COVID-19, a significant unmet need remains in patients who are unable to mount or maintain an adequate immune response to vaccination. Here we present additional results from 7-month follow-up period of the aforementioned study. Methods: In this randomized, double-blind, placebo-controlled Phase III trial, asymptomatic participants exposed to a SARS-CoV-2-infected household member were randomized 1:1 to a single SC dose of placebo or 1200 mg cas/imd (600 mg of each monoclonal antibody). Efficacy analyses include participants who were RT-qPCR negative for SARS-CoV-2 (no current infection) and seronegative for SARS-CoV-2 (no prior infection) at baseline. The trial consisted of a primary efficacy assessment period of 28 days (Month 1) and a 7-month follow-up period (Months 2-8). Results: Results from 842 placebo and 841 cas/imd RT-qPCR negative/seronegative enrolled participants (data through 04Oct2021, prior to emergence of Omicron) are presented. During the entirety of the 8-month study, cas/imd reduced the risk of symptomatic SARS-CoV-2 infections by 81.2% versus placebo (nominal P<0.0001;Table) and all SARS-CoV-2 infections (symptomatic and asymptomatic) by 68.2% versus placebo (nominal P<0.0001;Table). During Months 2-5, the risk of symptomatic and all infections were reduced by 100% and 89.5%, respectively (nominal P<0.0001). During Months 6-8 there was a resumption of symptomatic and all SARS-CoV-2 infections in the cas/imd group (19.9%;nominal P=0.6411 and 30.7%;nominal P=0.3967 risk reduction, respectively). Fewer cas/imd participants had a medically-attended visit versus placebo during the 8-months (1/841 [0.1%] vs 16/842 [1.9%], respectively). No new safety signals were identified for cas/imd during the follow-up period. Conclusion: During the 8-month study period, a 1200 mg SC dose of cas/imd prevented SARS-CoV-2 infections, with maximal protection through Month 5. The prolonged protection supports the use of cas/imd for the long-term prevention of COVID-19 against susceptible variants, offering a pre-exposure prophylaxis strategy for individuals who are unlikely to respond or be protected by vaccination.
ABSTRACT
Background: Passive immunization has a long history for infection prevention following exposure. We report results of a descriptive interim analysis from a study of an antibody “cocktail” of casirivimab with imdevimab (cas/imdev;formerly REGN-COV2) designed to bind non-competing epitopes of the viral spike protein, as a potential passive vaccine for the prevention of COVID-19 in people at risk of infection from household contact. Methods: In this ongoing Phase 3 study, asymptomatic participants exposed to a COVID-19-infected household member were randomized 1:1 to placebo or 1200 mg cas/imdev (600 mg of each antibody administered subcutaneously) within 96 hours of their household member testing positive. The analysis included participants who tested negative for SARS-CoV-2 by nasal, saliva, or nasopharyngeal swab and who were seronegative to SARS-CoV-2 antibodies at baseline. The proportion of participants who developed an RT-PCR-confirmed SARS-CoV-2 infection (asymptomatic or symptomatic) during the 1-month efficacy assessment period was summarized. Results: Initial results from the first evaluable 223 placebo and 186 cas/imdev participants who completed ≥29 days of the study are reported. Reduction in PCR-positive symptomatic disease was 100% (0/186 cas/imdev vs 8/223 placebo;OR 0.00 [CI 0.00, 0.69]). Reduction in any PCR-positive infection (symptomatic or asymptomatic) was 48% (10/186 vs 23/223;OR 0.49 [CI 0.20, 1.12]). Placebo-group participants had on average 100-fold higher peak viral load. In the cas/imdev group, viral RNA was not detected for longer than 1 week but was detected for 3-4 weeks in approximately 40% of placebo participants (Fig. 1). The proportions of infected participants with high viral loads (>10 4 copies/mL) were 13/21 placebo vs 0/9 cas/imdev. Total weeks of viral RNA detection and high viral load were 44 and 22 weeks in the placebo group vs 9 and 0 in the cas/imdev group. Total symptomatic weeks were 21 for placebo vs 0 for cas/imdev. A similar proportion of participants experienced at least 1 serious adverse event: placebo, 3/222 and cas/imdev, 1/186;none were deemed related to study treatment. Injection site reactions were similar: placebo, 1.4%;cas/ imdev, 2.6%. Conclusion: In this descriptive interim analysis of participants at risk of SARSCoV- 2 infection from household transmission, a subcutaneous dose of the cas/ imdev antibody cocktail prevented symptomatic infection, reduced overall infection, and decreased viral load and duration of viral RNA detection.