Subcutaneous REGEN-COV Antibody Combination in Early SARS-CoV-2 Infection

O’Brien, Meagan P.; Forleo-Neto, Eduardo; Sarkar, Neena; Isa, Flonza; Hou, Peijie; Chan, Kuo-Chen; Musser, Bret J.; Bar, Katharine J.; Barnabas, Ruanne V.; Barouch, Dan H.; Cohen, Myron S.; Hurt, Christopher B.; Burwen, Dale R.; Marovich, Mary A.; 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 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. (ClinicalTrials.gov number, NCT04452318.)