By: Daniela Farzadfar, PharmD,PGY-1 Resident at Long Island Jewish Medical Center

             In March 2020, the World Health Organization (WHO) declared coronavirus disease- 2019 (COVID-19) a global pandemic. ¹ To date, over 30 million cases of COVID-19 have been reported in the United States and drug companies have been scrambling to develop therapies for the treatment of COVID-19. ² In early November 2020, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for one of the first investigational monoclonal antibody therapies, bamlanivimab. Under the EUA, this agent is authorized for the treatment of mild-to-moderate COVID-19 in adult and pediatric patients with positive SARS- CoV-2 test results who are ≥ 12 years, weighing ≥ 40 kg, and who are at high risk for progressing to severe COVID-19 and/or hospitalization. High-risk patients include those with a body mass index (BMI) ≥ 35, chronic kidney disease, diabetes, an immunosuppressive disease, age ≥ 65 years, as well as those with certain other chronic medical conditions. It is also recommended that the drug be administered as soon as possible after a positive test for SARS- CoV-2 and within 10 days of symptom onset. ³

The benefits of bamlanivimab have not been observed in patients hospitalized due to COVID-19 and monoclonal antibodies may actually be associated with worse clinical outcomes in hospitalized patients requiring high flow oxygen or mechanical ventilation due to COVID-19. Bamlanivimab is, therefore, not authorized for use in patients who are hospitalized or require oxygen therapy due to COVID-19 or who require an increase in baseline oxygen flow rate due to COVID-19, specifically among those who are on chronic oxygen therapy due to an underlying non-COVID-19 related comorbidity. ³

How exactly does bamlanivimab work? Monoclonal antibodies are proteins made in a laboratory that mimic the immune system by fighting off harmful pathogens. ⁴ Bamlanivimab is a recombinant neutralizing human IgG1κ monoclonal antibody to the spike protein of SARS- COV-2. By binding to the spike protein, it blocks attachment to the human ACE2 receptor. ⁵ In this way, it is thought to neutralize the virus by blocking viral attachment. ³

Although the safety and efficacy of this agent is still being studied, the FDA says that bamlanivimab has been shown to reduce COVID-19 related hospital admissions or emergency room visits in patients at high risk for disease progression within 28 days after treatment when compared to placebo.

This statement is based on an interim analysis from a phase two randomized, double-blind, placebo-controlled clinical trial called BLAZE-1, which included 465 non-hospitalized adults with mild-to-moderate COVID-19 symptoms. One hundred and one of these patients received 700 mg of bamlanivimab, 107 received 2800 mg of bamlanivimab, 101 received 7000 mg of bamlanivimab, and 156 received a placebo within 3 days of obtaining the clinical sample for the first positive SARS-CoV-2 test. The primary endpoint was a change in viral load from baseline to day 11 for bamlanivimab vs. placebo while the secondary endpoint included COVID-19-related hospitalizations or emergency room visits within 28 days after treatment. Hospitalizations and ER visits occurred in 3% of patients at high risk for disease progression treated with bamlanivimab compared to 10% in those patients treated with placebo. The reduction in hospitalizations and ER visits as well the effects on safety were similar in patients receiving any of the 3 doses of bamlanivimab. ^{4, 6} The current recommended dose is 700 mg as a single dose administered as an intravenous infusion over 60 minutes or more. ⁵ In terms of safety, there is a risk of serious hypersensitivity reactions with bamlanivimab including anaphylaxis and infusion-related reactions, which may include fevers, chills, nausea, bronchospasm, hypotension, and angioedema. ³

While the results of the secondary endpoint seem promising, looking closer at the interim analysis of the BLAZE-1 trial, the results of the primary endpoint actually show that only one of the three doses of bamlanivimab accelerates the natural decrease in the viral load while the other doses had not done so by day 11. The 2800 mg dose of bamlanivimab demonstrated a statistically significant decrease in the viral load compared to placebo. The 700 mg and 7000 mg doses, however, showed smaller differences from placebo in the change from baseline viral load by day 11 and these results were actually not statistically significant. Yet, the interim analysis does indicate a reduction in hospitalizations and ER visits with all 3 doses of bamlanivimab when compared to placebo, which is of significance. ⁶

             The EUA for bamlanivimab presents providers with an additional tool for the treatment of COVID-19 and demonstrates the potential for development of new COVID-19 therapies. In fact, additional EUAs for monoclonal antibodies, casirivimab and imdevimab administered together as well as bamlanivimab and etesevimab to be used together for the treatment of mild- to-moderate COVID-19, have also been recently issued. ^{7, 8} Although these agents are still being evaluated and have not yet been approved, this progress in the development and access of new COVID-19 therapies has shown some promise.

References:

1. World Health Organization, 2020. Archived: WHO Timeline – COVID-19. Who.int. https://www.who.int/news/item/27-04-2020-who-timeline—covid-19. Accessed 11/27/2020.
2. Centers for Disease Control and Prevention, 2020. COVID-19 Cases, Deaths, And Trends In The US | CDC COVID Data Tracker. Centers for Disease Control and Prevention. https://covid.cdc.gov/covid-data-tracker/#cases_casesper100klast7days. Accessed 4/1/2021.
3. Lilly, 2020. Bamlanivimab (BAM) EUA Treatment For COVID-19 | HCP | Lilly COVID-19 Treatment. Covid19.lilly.com. https://www.covid19.lilly.com/bamlanivimab/hcp?gclid=CjwKCAiA5IL- BRAzEiwA0lcWYga2doHyI_GWqdnmkWHQ2xecZ42oc9LANAF9cYWffCpGP_uTctaqQxoC6 64QAvD_BwE. Accessed 11/27/2020.
4. Food and Drug Administration, 2020. FDA Authorizes Monoclonal Antibody For Treatment Of COVID-19. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press- announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibody-treatment- covid-19. Published 11/9/2020. Accessed 11/27/2020.
5. Bamlanivimab. In: Lexi-drugs Online. Hudson, OH: Lexicomp, Inc.; 2020 Available from http://online.lexi.com. Updated 11/24/2020. Accessed 11/27/2020.
6. Chen P, Nirula A, Heller B, et al. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19 [published online ahead of print, 2020 Oct 28]. N Engl J Med. doi:10.1056/NEJMoa2029849
7. Food and Drug Administration, 2020. Coronavirus (COVID-19) Update: FDA Authorizes Monoclonal Antibodies For Treatment Of COVID-19. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda- authorizes-monoclonal-antibodies-treatment-covid-19. Published 11/21/2020. Accessed 11/27/2020.
8. Food and Drug Administration, 2021. Coronavirus (covid-19) UPDATE: FDA Authorizes monoclonal antibodies for treatment of covid-19., U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda- authorizes-monoclonal-antibodies-treatment-covid-19-0. Published 02/09/2021. Accessed 04/01/2021

Published by Rho Chi Post