Subcutaneous REGEN-COV Antibody Combination for Covid-19 Prevention

O’Brien, Meagan P.; Forleo-Neto, Eduardo; Musser, Bret J.; Isa, Flonza; Chan, Kuo-Chen; Sarkar, Neena; Bar, Katharine J.; Barnabas, Ruanne V.; Barouch, Dan H.; Cohen, Myron S.; Hurt, Christopher B.; Burwen, Dale R.; Marovich, Mary A.; Hou, Peijie; Heirman, Ingeborg; Davis, John D.; Turner, Kenneth C.; Ramesh, Divya; Mahmood, Adnan; Hooper, Andrea T.; Hamilton, Jennifer D.; Kim, Yunji; Purcell, Lisa A.; Baum, Alina; Kyratsous, Christos A.; Krainson, James; Perez-Perez, Richard; Mohseni, Rizwana; Kowal, Bari; DiCioccio, A. Thomas; Stahl, Neil; Lipsich, Leah; Braunstein, Ned; Herman, Gary; Yancopoulos, George D.; Weinreich, David M.

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 (>10(4) 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.)