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Safety and Efficacy of Combination SARS-CoV-2 Neutralizing Monoclonal Antibodies Amubarvimab Plus Romlusevimab in Nonhospitalized Patients With COVID-19
Journal article   Open access   Peer reviewed

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

Teresa H Evering, Kara W Chew, Mark J Giganti, Carlee Moser, Mauricio Pinilla, David Alain Wohl, Judith S Currier, Joseph J Eron, Arzhang Cyrus Javan, Rachel Bender Ignacio, …
Annals of internal medicine, Vol.176(5), pp.658-666
05/01/2023
DOI: 10.7326/M22-3428
PMCID: PMC10150320
PMID: 37068272
url
https://pmc.ncbi.nlm.nih.gov/articles/PMC10150320/View
Published (Version of record) Open Access

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.
 Antibodies 1103 Clinical Sciences (for) 1117 Public Health and Health Services (for) 3 Good Health and Well Being (sdg) 32 Biomedical and Clinical Sciences (for-2020) 3202 Clinical Sciences (for-2020) 6.1 Pharmaceuticals (hrcs-rac) ACTIV-2/A5401 Study Team Adult (mesh) Biotechnology (rcdc) Clinical Research (rcdc) Clinical Trials and Supportive Activities (rcdc) Coronaviruses (rcdc) COVID-19 (mesh) Double-Blind Method (mesh) Emerging Infectious Diseases (rcdc) Female (mesh) Health Disparities (rcdc) Humans (mesh) Infection (hrcs-hc) Infectious Diseases (rcdc) Male (mesh) Middle Aged (mesh) Minority Health (rcdc) Monoclonal (mesh) Patient Safety (rcdc) Prevention (rcdc) SARS-CoV-2 (mesh) Viral (mesh)

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