In November of 2020, the U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) to allow for the use of bamlanivimab (LY-CoV555). Currently, this is an unapproved product but is authorized in the treatment of mild to moderate coronavirus disease 2019 (COVID- 19).1
EUA or Emergency Use Authorization is a guidance document released by the FDA to outline the availability of medical countermeasures (MCM). These agents or products can only be authorized for use after justification from the secretary for the Department of Health and Human Services. MCMs can include unapproved agents or products to diagnose, treat, or prevent serious or life-threatening diseases or conditions involving chemical, biological, radiological, and nuclear (CBRN) agents. Multiple EUAs can be issued to meet the needs of the current state of affairs.2
Bamlanivimab is a human immunoglobulin G-1 (IgG1) monoclonal antibody that neutralizes the spike protein of SARS-CoV-2 which causes COVID-19. This helps to block the viral attachment to the human angiotensin-converting enzyme 2 (ACE2) receptor, which is said to be a binding site for SARS-CoV-2. Bamlanivimab is most efficacious if administered as soon as possible following a positive result of direct SARS-CoV-2 viral testing and within 10 days of symptom onset.1
The United States government has purchased 300,000 doses of bamlanivimab and is allocating doses based on the confirmed COVID-19 cases in each state. It is important to note that although the drug itself will not have out-of-pocket costs, healthcare facilities may elect to charge a fee to prepare and administer the product. Each week, the state health departments will allocate doses by choosing facilities that are most accessible and most effective in minimizing infection transmission. If it is later determined that more doses are needed, the government can purchase up to 650,000 additional doses through the end of June 2021.3
The EUA that permits the use of bamlanivimab has imposed stringent inclusion criterion. Generally, bamlanivimab is for the treatment of mild to moderate COVID-19 in patients 12 years and older and at least 40 kg with a positive result of direct SARS-CoV-2 viral testing who are at high risk for progressing to severe and or hospitalization.1 High risk patients are described in Table 1. Bamlanivimab can be used in patients hospitalized for reasons other than COVID-19 as long as they met the general criteria outlined in the EUA. Dosing recommendation for bamlanivimab is 700 mg in normal saline bringing the total infusion volume to 200 mL.3
Table 1: High Risk Criteria for Use of Bamlanivimab3
High risk for progressing to severe COVID-19 and/or hospitalization is defined as patients who meet at least one of the following criteria:
● Have a body mass index (BMI) ≥ 35
● Have chronic kidney disease
● Have diabetes
● Have immunosuppressive disease
● Are currently receiving immunosuppressive treatment
● Are ≥ 65 years of age
● Are ≥ 55 years of age AND have
○ cardiovascular disease, OR
○ hypertension, OR
○ chronic obstructive pulmonary disease/other chronic respiratory disease
● Are 12 – 17 years of age AND have
○ BMI ≥ 85th percentile for their age and gender based on CDC growth charts, OR
○ sickle cell disease, OR
○ congenital or acquired heart disease, OR
○ neurodevelopmental disorders, for example, cerebral palsy, OR
○ a medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19), OR
○ asthma, reactive airway or other chronic respiratory disease that requires daily medication for control
Bamlanivimab has not been authorized for use in patients who are hospitalized due to COVID-19, require oxygen therapy due to COVID-19, or require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity.1
In the SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19 (BLAZE-1) trial, 452 participants were randomly assigned to receive bamlanivimab 700 mg, 2800 mg, 7000 mg, or placebo. Participants of this Phase 2 trial were at least 18 years old at the time of randomization, were not hospitalized, and had one or more mild or moderate COVID-19 symptoms. Patients were randomized to receive an infusion of bamlanivimab or placebo within three days of the first positive SARS-CoV-2 test results. The primary and secondary outcomes are described in Tables 2 and 3 (see end of article). From the trial, it was determined that the 2800 mg and 7000 mg doses produced no meaningful differences in viral load and clinical outcomes when compared to the 700 mg dose. All three doses demonstrated a flat exposure-response relationship in efficacy.4
In this Phase 2 trial, patients were followed for at least 28 days following treatment. Adverse events occurred in 23% of patients in the bamlanivimab arm and 26% of patients in the placebo arm. Adverse events include nausea, diarrhea, dizziness, headache, pruritus, and vomiting. Serious adverse events occurred in one patient in the placebo arm and in no patients in the bamlanivimab arm.1
Bamlanivimab is preservative-free and must be administered within 24 hours when refrigerated and 7 hours if at room temperature; this time must also include administration time. The minimum infusion time is 60 minutes at a rate of 200 mL/hr. A polyvinyl chloride (PVC) infusion set containing a 0.20/0.22 micron in-line polyethersulfone (PES) filter must be used during administration. Each healthcare facility will have to determine best practices on how to administer this agent since this drug will likely be administered in an outpatient health care setting. Patients must be monitored during administration and for up to one hour following treatment. Providers must have immediate access to medication to treat anaphylaxis or a severe infusion reaction.1
In order to mitigate the risks of using bamlanivimab, requirements must be met before use. Bamlanivimab can only be used in the treatment of mild to moderate COVID-19 in patients 12 years and older and at least 40 kg with a positive result of direct SARS-CoV-2 viral testing who are at high risk for progressing to severe and or hospitalization. Healthcare providers must communicate information consistent with the “Fact Sheet for Patients, Parents, and Caregivers” prior to the patient receiving bamlanivimab. Patients need to be informed by their healthcare provider that bamlanivimab is an unapproved drug and discuss alternative agents to bamlanivimab. Currently, casirivimab plus imdevimab are authorized for use by another EUA to treat patients in a similar condition. Lastly, healthcare providers must report all medication errors and serious adverse events within seven days of onset to FDA MedWatch and provide a copy to Eli Lilly.1
Currently, there is only one agent that has been FDA approved in the treatment of COVID-19. Remdesivir is only indicated for the treatment of COVID-19 patients requiring hospitalization.5 Bamlanivimab, under EUA, has been authorized by the FDA for treatment of mild to moderate COVID-19 in high-risk patients. Pharmacists, as well as the rest of the healthcare team, should be aware of the authorized use indications for bamlanivimab in order to select appropriate high-risk patients to receive the medication.
- Fact sheet for healthcare providers: emergency use authorization (EUA) of bamlanivimab. U.S. Food and Drug Administration. https://www.fda.gov/media/143603/download. Accessed November 20, 2020.
- Emergency Use Authorization of Medical Products. U.S. Food and Drug Administration. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-medical-products-and-related-authorities. Accessed November 28, 2020.
- Frequently Asked Questions on the Emergency Use Authorization for Bamlanivimab. U.S. Food and Drug Administration. https://www.fda.gov/media/143605/download. Accessed November 28, 2020.
Chen P, Nirula A, Heller B, et al. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients With Covid-19 [Epub ahead of print October 28, 2020]. N Engl J Med. 2020.
- VEKLURY® (remdesivir) [package insert]. Foster City, CA:Gilead Sciences, Inc., October 2020.