• 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, David Margolis, Qing Zhu, Ji Ma, Lijie Zhong, Li Yan, Ulises D'Andrea Nores, Keila Hoover, Bharat Mocherla, Manish C Choudhary, Rinki Deo, Justin Ritz, William A Fischer, Courtney V Fletcher, Jonathan Z Li, Michael D Hughes, Davey Smith, Eric S Daar, and ACTIV-2/A5401 Study Team.
• Weill Cornell Medicine, New York, New York (T.H.E.).
• Ann. Intern. Med. 2023 May 1; 176 (5): 658666658-666.

BackgroundDevelopment 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.ObjectiveTo assess the safety and efficacy of amubarvimab plus romlusevimab.DesignRandomized, placebo-controlled, phase 2 and 3 platform trial. (ClinicalTrials.gov: NCT04518410).SettingNonhospitalized patients with COVID-19 in the United States, Brazil, South Africa, Mexico, Argentina, and the Philippines.PatientsAdults within 10 days onset of symptomatic SARS-CoV-2 infection who are at high risk for clinical progression.InterventionCombination of monoclonal antibodies amubarvimab plus romlusevimab or placebo.MeasurementsNasopharyngeal and anterior nasal swabs for SARS-CoV-2, COVID-19 symptoms, safety, and progression to hospitalization or death.ResultsEight-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.LimitationThe study population was mostly unvaccinated against COVID-19 and enrolled before the spread of Omicron variants and subvariants.ConclusionAmubarvimab 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 SourceNational Institute of Allergy and Infectious Diseases of the National Institutes of Health.

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