In the battle against COVID-19, vaccines have taken center stage. This is especially true with the recent news about the vaccines from Pfizer/BioNTech and Moderna. While vaccines are likely the most important tool to curtail the spread of the virus, an effective means to treat those who will be diagnosed with the disease is still critical.
The U.S. Food & Drug Administration (FDA) has recently provided emergency use authorization (EUA) for two treatment methods using neutralizing monoclonal antibodies: Eli Lilly and Company’s bamlanivimab and Regeneron’s REGN-COV2 cocktail.1,2 These therapies work in similar ways; both target the SARS-CoV-2 spike protein with antibodies to inhibit the ability of virions to exploit the ACE2 receptor and infect human cells. This results in a protective shield of monoclonal antibodies surrounding the virions, which effectively neutralizes them.
One point where the therapies differ is the number of monoclonal antibodies used. Bamlanivimab is the sole antibody present in the Eli Lilly and Company treatment, whereas REGN-COV2 combines two (hence the cocktail part) antibodies—casirivimab and imdevimab. Eli Lilly and Company currently have an antibody cocktail of their own in development.
An EUA means that while the FDA has not approved the therapy, it has found that the known and potential risks are worth the potential benefits. With these authorizations, the FDA hopes to provide some relief to a healthcare system stretched thin by the winter surge.
The EUA afforded to both are similar; the therapies are approved to treat mild to moderate COVID-19 infections in adults and children 12 and up who are considered a high risk to develop severe symptoms and/or are likely to need hospitalization. Both therapies have been shown to reduce patient need for hospitalization and medical care for up to a month after treatment.
Although both therapies show promise, they are not without their challenges and limitations. For example, administering the antibodies is not quick and simple. Both therapies are given intravenously, and the process takes approximately one hour. After the transfusion is complete, the patient must be monitored for a minimum of one additional hour. In a system already strained for time and resources—human and otherwise—this presents a significant challenge.
Administration of the treatment is possibly overshadowed by a second limitation of the therapies: timing. Both therapies have a relatively small window in which they must be given. That window is within approximately ten days after a positive test or symptom onset and before symptoms have become too severe. Beyond this window, the virus may simply have too strong of a foothold for the therapies to improve outcomes.
This is problematic because many people are taking advantage of mass-testing facilities and may never see a healthcare provider who can assess their risk. They may not reach out to a healthcare provider until their symptoms have become severe. Healthcare providers who do see high-risk patients within that window must convince their patients to take a relatively unknown, somewhat invasive treatment at a time when they may not be feeling very ill. However, once symptoms become severe, bamlanivimab and REGN-COV2 are no longer treatment options. In fact, both therapies may worsen the outcome of those with a severe COVID-19 infection.1,2
Supply of the therapeutics themselves is another challenge. Creating neutralizing monoclonal antibodies is complicated and requires much time, effort, expense, and expertise. Consequently, scaling up production to anticipated need is not simple. Both Eli Lilly and Company and Regeneron have invested in operations to step-up production levels to meet global demand. Eli Lilly and Company anticipate they will have one million doses of bamlanivimab by the end of 2020. Regeneron hopes to have 300,000 doses produced by the end of January 2021 and two million doses per year thereafter.
Neutralizing monoclonal antibodies are just one of the potential therapeutic options being explored for COVID-19 treatment. In addition to other treatment options, including anti-inflammatory therapeutics and immune system stimulators, there are currently 70+ other antibody treatments under evaluation.3 Given the urgency of the situation and the highly competitive atmosphere, it’s imperative for developers to find a fast and reliable way to evaluate antiviral compounds and antibodies.
A recently developed assay, called the plaque reduction microneutralization (PRMNT) assay, has shown to be an effective method to screen compounds and antibodies.4 Using an Odyssey® Imaging System and near-infrared fluorescence imaging, the researchers were able to simultaneously examine both the neutralizing abilities and potential toxicity 24 hours post-infection.4 Such a rapid and versatile approach offers the potential to improve therapeutic development timelines.
No treatment is perfect, and treatment options for those suffering from a severe infection are still required. Despite their limitations, bamlanivimab and REGN-COV2 have the potential to save many lives directly, through the patients treated with these therapies, and indirectly by easing the overall burden on the healthcare system.
References
- U.S. Food & Drug Administration. (2020, November 9). Coronavirus (COVID-19) Update: FDA Authorizes Monoclonal Antibody for Treatment of COVID-19. Press release. Retrieved December 2, 2020 from https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibody-treatment-covid-19
- U.S. Food & Drug Administration. (2020, November 21). Coronavirus (COVID-19) Update: FDA Authorizes Monoclonal Antibodies for Treatment of COVID-19. Press release. Retrieved December 2, 2020 from https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibodies-treatment-covid-19
- BIO. (n.d.). BIO COVID-19 Therapeutic Development Tracker. Retrieved December 2, 2020 from https://www.bio.org/policy/human-health/vaccines-biodefense/coronavirus/pipeline-tracker
- Park, J-G., Oladunni, F.S., Chiem, K., Ye, C., Pipenbrink, M., Moran, T., Walter, M.R., Kobie, J., and Martinez-Sobrido, L. (2021). Rapid in vitro assays for screening neutralizing antibodies and antivirals against SARS-CoV-2. Journal of Virological Methods, 287. DOI: 10.1016/j.jviromet.2020.113995
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