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.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has issued an emergency use authorization (EUA) for an investigational monoclonal antibody therapy for mild-to-moderate COVID-19.1 Bamlanivimab (LY-Cov555) is a neutralizing recombinant IgG1 monoclonal antibody that connects to the receptor-binding domain of the spike protein of SARS-CoV-2. The drug blocks attachment and entry of the virus into human cells.2 Researchers derived the drug using convalescent plasma obtained from a patient with COVID-19.3
Bamlanivimab should be used in an outpatient setting to treat mild-to-moderate COVID-19 in adults and pediatric COVID-19 patients (age ≥ 12 years and weight at least 40 kg) who are at high risk for developing severe COVID-19 and/or landing in the hospital.2 This includes patients with a BMI ≥ 35 kg/m2, age ≥ 65 years, CV disease, diabetes, and COPD. The drug is not authorized for patients who are hospitalized, require oxygen, or those who required an increase in baseline oxygen flow rate while on chronic oxygen therapy for non-COVID-19-related conditions.
The recommended dose is a single 700-mg shot administered intravenously over 60 minutes as soon as possible after a positive viral test for SARS-CoV-2 and within 10 days of symptom onset. It should be given in a setting where there is immediate access to treatment of severe infusion reaction, such as anaphylaxis.2 Bamlanivimab is supplied as a 700-mg/20-mL vial.
Bamlanivimab provides a treatment option for patients with mild-to-moderate disease as drug evaluations continue. Preliminary data suggest the drug may reduce hospitalization or ED visits and lower symptom severity.3
Bamlanivimab does not appear to be effective for patients hospitalized with COVID-19, those who require oxygen for COVID-19, or for those who need oxygen for non-COVID-19 conditions. The drug may lead to worse clinical outcomes when given to patients hospitalized with COVID-19 who are on high-flow oxygen or mechanical ventilation.2
The EUA was based on an interim analysis of an ongoing randomized, double-blind, placebo-controlled, Phase II study of subjects who were not hospitalized and had mild-to-moderate symptoms.1,3 Researchers randomized subjects into four groups: bamlanivimab as a single dose (700 mg, 2,800 mg, or 7,000 mg) or placebo (administered within three days after a positive SARS-CoV-2 test.3 The primary outcome was change from baseline in SARS-CoV-2 viral load at day 11 (± 4 days) as measured by nasopharyngeal swab and reverse transcriptase polymerase chain reaction. Secondary endpoints were hospitalization/ED visit (28 days after treatment), symptom severity, and safety assessment. The most significant findings in the analysis of 465 subjects was the difference in COVID-related hospitalizations between bamlanivimab-treated and placebo-treated patients in those at high risk for disease progression, hospitalization, and ED visits (3% vs. 10%).1 Overall viral load declined in all groups, with no clear difference at day 11 (although favorability leaned toward bamlanivimab at day 3). Those randomized to bamlanivimab exhibited slightly lower severity of symptoms from day 2 to day 6. A safety assessment did not reveal any significant serious events vs. placebo. No clear differences in primary or secondary endpoints were observed among the different doses of bamlanivimab. More than 850 subjects have received bamlanivimab in clinical trials. There has been one anaphylaxis reaction and one serious infusion-related reaction.2 A study of the efficacy of dual therapy (bamlanivimab and remdesivir) in hospitalized subjects has ended, with researchers citing that benefit is unlikely.4
Bamlanivimab is the first monoclonal antibody to be granted an EUA for nonhospitalized patients with mild-to-moderate disease. Preliminary data suggest it may reduce the rate of hospitalization. Regeneron has developed a “cocktail” of two polyclonal antibodies (casirivimab and imdevimab, REGN-COV2) that targets two different sites of SARS-CoV-2. The manufacturer received an EUA on Nov. 21.5 The most current NIH COVID-19 treatment guidelines state “there are insufficient data to recommend either for or against the use of bamlanivimab for the treatment of outpatients with mild to moderate COVID-19” and that the drug should not be considered the standard of care.6 The Infectious Diseases Society of America’s recently released guidelines conditionally caution against routine use of bamlanivimab.7
- U.S. Food & Drug Administration. Coronavirus (COVID-19) update: FDA authorizes monoclonal antibody for treatment of COVID-19. Nov. 9, 2020.
- U.S. Food & Drug Administration. Bamlanivimab EUA letter of authorization. Nov. 10, 2020.
- Chen P, Nirula A, Heller B, et al. SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with COVID-19. N Engl J Med 2020; Oct 28;NEJMoa2029849. doi: 10.1056/NEJMoa2029849. [Online ahead of print].
- Romo V. Eli Lilly ends antibody trial in hospitalized COVID-19 patients, other trials go on. National Public Radio. Oct. 26, 2020. https://bit.ly/3l0bjpv
- U.S. Food & Drug Administration. Coronavirus (COVID-19) update: FDA authorizes monoclonal antibodies for treatment of COVID-19. Nov. 21, 2020.
- National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. Nov. 24, 2020.
- Infectious Diseases Society of America. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19. Recommendation 13: Bamlanivimab vs. no bamlanivimab for non-hospitalized patients. Section last reviewed and updated Nov. 18, 2020.