BackgroundContinued SARS-CoV-2 infections and COVID-19-related hospitalizations highlight the need for effective anti-viral treatments in the outpatient setting. In a descriptive interim analysis of the phase 1/2 portion of a double-blind phase 1/2/3 trial in COVID-19 outpatients conducted between June 16, 2020 and September 4, 2020, REGEN-COV(R) (casirivimab plus imdevimab) antibody combination reduced SARS-CoV-2 viral load versus placebo. MethodsThis final phase 1/2 analysis comprises 799 outpatients, including 275 from the previous descriptive analysis (group-1) and 524 from phase 2 (group-2). Patients were randomized (111) to placebo, REGEN-COV 2400mg, or REGEN-COV 8000mg. Prespecified hierarchical analyses of virologic endpoints were performed in group-2. The proportion of patients with [≥]1 COVID-19-related medically attended visit (MAV) through day 29 was assessed in group-1+2. Efficacy was assessed in patients confirmed SARS-CoV-2-positive by baseline nasopharyngeal RT-qPCR. Safety was assessed in all treated patients. ResultsData from 799 outpatients enrolled from June 16, 2020 to September 23, 2020 are reported. Time-weighted average daily reduction in viral load through day 7 was significantly greater in the REGEN-COV combined 2400mg+8000mg group versus placebo in patients with baseline viral load >107 copies/mL (prespecified primary endpoint) -0.68 log10 copies/ml (95% CI, -0.94 to -0.41; P<.0001). This reduction was - 0.73 (P<.0001) and -0.36 (P=.0003) log10 copies/mL in serum antibody-negative patients and in the overall population, respectively. REGEN-COV reduced the proportion of patients with [≥]1 COVID-19-related MAV versus placebo (2.8% [12/434] REGEN-COV combined dose group versus 6.5% [15/231] placebo; P=.024; relative risk reduction [RRR]=57%); in patients with [≥]1 risk factor for hospitalization, the treatment effect was more pronounced (RRR=71%). Adverse events were similar across groups. ConclusionsIn COVID-19 outpatients enrolled prior to the widespread circulation of delta and omicron variants, treatment with REGEN-COV significantly reduced viral load and COVID-19-related MAVs.