By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
The FDA issued an emergency use authorization (EUA) for a second monoclonal antibody combination to treat mild-to-moderate COVID-19. Bamlanivimab and etesevimab (BAM/ETE) are recombinant neutralizing human IgG1k monoclonal antibodies directed at the spike protein of SARS-CoV-2.1 They bind to different but overlapping targets in the receptor binding domain of the spike protein. This combination is expected to lower the risk of emergent resistance to SARS-CoV-2 vs. administering bamlanivimab alone.
BAM/ETE should be prescribed to treat mild-to-moderate COVID-19 in adults and pediatric patients (age 12 years and older, weight at least 40 kg) who test positive for COVID-19 and are at high risk for progressing to severe disease and/or hospitalization.1 High risk includes comorbidities (e.g., cardiovascular disease, diabetes, immunosuppressive disease, chronic kidney disease, and respiratory disease), age ≥ 65 years, obesity (body mass index ≥ 30 kg/m2), or on immunosuppressive treatment.
BAM/ETE is not authorized for use in patients who are hospitalized because of COVID-19, who require oxygen therapy or increase from baseline oxygen because of COVID-19, or those who are on chronic oxygen therapy.
The recommended dose is BAM (700 mg) and ETE (1,400 mg), administered by intravenous infusion together as soon as possible after a positive viral test and within 10 days of symptom onset.1 BAM and ETE each are available as 700 mg/20 mL single-use vials.
BAM/ETE cuts the risk of emergent resistant variants of SARS-CoV-2 and treatment failure compared to BAM alone.1 It also provides another therapeutic option to casirivimab and imdevimab (the first monoclonal antibody therapy to receive an FDA EUA to treat COVID-19) for mild-to-moderate COVID-19.
BAM/ETE is not authorized for use in hospitalized patients or those who require oxygen therapy, which limits when the combination can be used. Serious hypersensitivity reactions, including anaphylaxis, have been observed with BAM.
The EUA was based on an interim analysis of a Phase III clinical trial. There, investigators sought to assess the effect of BAM as monotherapy or in combination with ETE in high-risk patients with mild-to-moderate COVID-19. Initially, this work was carried out in an ongoing Phase II/III trial.2 In the interim analysis, of 1,035 nonhospitalized adults, 518 received a single infusion of BAM (2,800 mg) and ETE (2,800 mg) and 517 received placebo.1 The primary endpoint was COVID-19-related hospitalization or death by any cause during 29 days of follow-up. Thirty-six hospitalization/deaths occurred in the placebo arm vs. 11 in the BAM/ETE arm. This represented a 70% risk reduction (P = < 0.001). There were 10 deaths in the placebo group vs. no deaths in the BAM/ETE group. BAM/ETE patients also recorded faster time to symptom resolution (median six days vs. eight days for placebo). The authorized dose of 700 mg/1,400 mg was based on comparable virological response to the 2,800 mg/2,800 mg dose as well as pharmacokinetic/pharmacodynamic modeling.2
Contrasted against BAM/ETE, the casirivimab/imdevimab combination binds to different (but not overlapping) regions of the SARS-CoV-2 receptor binding domain.1,3 This combination reduced the risk of hospitalization and ED visits in high-risk patients, but did not show a significant difference in median time to symptom improvement (five days vs. six days).3 Because of this, the current Infectious Diseases Society of America (IDSA) guidelines suggest the use of BAM/ETE in patients with mild to moderate COVID-19 at high risk for progression to severe disease.4 IDSA considers the data strongest for BAM/ETE.
- U.S. Food & Drug Administration. Frequently asked questions on the emergency use authorization for bamlanivimab and etesevimab. Updated March 24, 2021.
- Gottlieb RL, Nirula A, Chen P, et al. Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: A randomized clinical trial. JAMA 2021;325:632-644.
- U.S. Food & Drug Administration. Coronavirus (COVID-19) update: FDA authorizes monoclonal antibodies for treatment of COVID-19. Feb. 9, 2021.
- Infectious Diseases Society of America. Monoclonal antibodies. Updated March 12, 2021.