REGN-COV2 antibodies prevent and treat SARS-CoV-2 infection in rhesus macaques and hamsters

Abstract

An urgent global quest for effective therapies to prevent and treat coronavirus disease 2019 (COVID-19) is ongoing. We previously described REGN-COV2, a cocktail of two potent neutralizing antibodies (REGN10987 and REGN10933) that targets nonoverlapping epitopes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. In this report, we evaluate the in vivo efficacy of this antibody cocktail in both rhesus macaques, which may model mild disease, and golden hamsters, which may model more severe disease. We demonstrate that REGN-COV-2 can greatly reduce virus load in the lower and upper airways and decrease virus-induced pathological sequelae when administered prophylactically or therapeutically in rhesus macaques. Similarly, administration in hamsters limits weight loss and decreases lung titers and evidence of pneumonia in the lungs. Our results provide evidence of the therapeutic potential of this antibody cocktail.

Fig. 1. Prophylactic efficacy of REGN-COV2 in the rhesus macaque model of SARS-CoV-2 infection (NHP study 1).

(A) Overview of study design. d, day. (B) Impact of REGN-COV2 prophylaxis on viral gRNA and sgRNA in nasopharyngeal (NP) swabs and BAL fluid. The numbers in the graph legends represent animal codes. The dotted lines indicate limit of detection (LOD = 50 GE/ml for gRNA and LOD = 50 SGE/ml for sgRNA). For detailed statistical analysis, refer to tables S2 and S3. GE, genomic equivalents; SGE, subgenomic equivalents.

Fig. 2. Prophylactic and therapeutic efficacy of REGN-COV2 in the rhesus macaque model of SARS-CoV-2 infection (NHP study 2).

(A) Overview of study design. (B) Impact of REGN-COV2 prophylaxis on viral gRNA and sgRNA in nasopharyngeal swabs and oral swabs [Study A, as shown in (A)]. (C) Impact of REGN-COV2 treatment on viral gRNA and sgRNA in nasopharyngeal swabs and oral swabs [Study B, as shown in (A)]. In (B) and (C), the numbers in the graph legends represent animal codes, and the dotted lines indicate limit of detection (LOD = 800 GE/ml for gRNA and LOD = 800 SGE/ml for sgRNA). (D) Representative images of histopathology in lungs of treated and placebo animals. The black arrows point to inflammatory cells. For detailed statistical analysis, refer to tables S2 and S3.

Fig. 3. Efficacy of REGN-COV2 in treatment and prophylaxis in the golden Syrian hamster model of SARS-CoV-2 infection.

(A) Overview of study design. (B) Impact of REGN-COV2 on weight loss in prophylaxis and treatment groups. Error bars represent mean with error. IgG1, immunoglobulin G1. (C) Impact of REGN-COV-2 prophylaxis on levels of gRNA and sgRNA in hamster lungs (7 days after infection). No statistical significance was observed between any treatment groups and placebo. The dotted lines indicate limit of detection (LOD = 200 GE/ml for gRNA and LOD = 200 SGE/ml for sgRNA), and error bars represent median with 95% confidence intervals. (D) Impact of REGN-COV2 prophylaxis on percent area of lung exhibiting pathology typical of pneumonia (****p < 0.0001 indicates significant differences). Error bars represent median with 95% confidence intervals. For detailed statistical analysis, refer to tables S4 and S5.