Safety and Efficacy of Combination SARS-CoV-2 Neutralizing Monoclonal Antibodies Amubarvimab Plus Romlusevimab in Nonhospitalized Patients With COVID-19

Objective: To assess the safety and efficacy of amubarvimab plus romlusevimab. Design: Randomized, placebo-controlled, phase 2 and 3 platform trial. (ClinicalTrials.gov: NCT04518410) Setting: Nonhospitalized patients with COVID-19 in the United States, Brazil, South Africa, Mexico, Argentina, and the Philippines. Patients: Adults within 10 days onset of symptomatic SARSCoV-2 infection who are at high risk for clinical progression. Intervention: Combination of monoclonal antibodies amubarvimab plus romlusevimab or placebo. Measurements: Nasopharyngeal and anterior nasal swabs for SARS-CoV-2, COVID-19 symptoms, safety, and progression to hospitalization or death. Results: Eight-hundred and seven participants who initiated the study intervention were included in the phase 3 analysis. Median age was 49 years (quartiles, 39 to 58); 51% were female, 18% were Black, and 50% were Hispanic or Latino. Median time from symptom onset at study entry was 6 days (quartiles, 4 to 7). Hospitalizations and/or death occurred in 9 (2.3%) participants in the amubarvimab plus romlusevimab group compared with 44 (10.7%) in the placebo group, with an estimated 79% reduction in events (P < 0.001). This reduction was similar between participants with 5 or less and more than 5 days of symptoms at study entry. Grade 3 or higher treatment-emergent adverse events through day 28 were seen less frequently among participants randomly assigned to amubarvimab plus romlusevimab (7.3%) than placebo (16.1%) (P < 0.001), with no severe infusion reactions or drug-related serious adverse events. Limitation: The study population was mostly unvaccinated against COVID-19 and enrolled before the spread of Omicron variants and subvariants. Conclusion: Amubarvimab plus romlusevimab was safe and significantly reduced the risk for hospitalization and/or death among nonhospitalized adults with mild to moderate SARSCoV-2 infection at high risk for progression to severe disease.

Automated summary

This randomized controlled trial assessed the safety and efficacy of amubarvimab plus romlusevimab. The combination treatment significantly reduced the risk of hospitalization and/or death among nonhospitalized adults with mild to moderate SARSCoV-2 infection at high risk for progression to severe disease.