RESUMO
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 (1:1:1) 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.
RESUMO
Monoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option against COVID-19. As rapidly emerging virus mutants are becoming the next major concern in the fight against the global pandemic, it is imperative that these therapeutic treatments provide coverage against circulating variants and do not contribute to development of treatment emergent resistance. To this end, we investigated the sequence diversity of the spike protein and monitored emergence of minor virus variants in SARS-COV-2 isolates found in COVID-19 patients or identified from preclinical in vitro and in vivo studies. This study demonstrates that a combination of non-competing antibodies, REGEN-COV, not only provides full coverage against current variants of concern/interest but also protects against emergence of new such variants and their potential seeding into the population in a clinical setting.
