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

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 ( < 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%) ( < 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.