{"doi":"10.7326/m22-3428","title":"Safety and Efficacy of Combination SARS-CoV-2 Neutralizing Monoclonal Antibodies Amubarvimab Plus Romlusevimab in Nonhospitalized Patients With COVID-19","abstract":"Background: Development of safe and effective SARS-CoV-2 therapeutics is a high priority. Amubarvimab and romlusevimab are noncompeting anti–SARS-CoV-2 monoclonal antibodies with an extended half-life. 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 SARS-CoV-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 SARS-CoV-2 infection at high risk for progression to severe disease. Primary Funding Source: National Institute of Allergy and Infectious Diseases of the National Institutes of Health.","journal":"Annals of Internal Medicine","year":2023,"id":325386,"datarank":0.7847535886315482,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"self_citation_contribution":0.519860385419959,"citation_network_contribution":0.26489320321158916,"self_endowment_contribution":0.519860385419959,"citer_contribution":0.26489320321158916,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":16,"citers_with_citation_signal":15,"citers_with_endowment":15,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9616,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT04518410"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":315361,"name":"Kara W Chew","orcid":"0000-0003-4865-4348","position":1,"is_corresponding":false},{"id":387866,"name":"Mark J Giganti","orcid":"0000-0003-2255-9756","position":2,"is_corresponding":false},{"id":419481,"name":"Carlee Moser","orcid":"0000-0001-5601-9112","position":3,"is_corresponding":false},{"id":474421,"name":"Mauricio Pinilla","orcid":null,"position":4,"is_corresponding":false},{"id":340150,"name":"David A. 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