Casirivimab and imdevimab represent a combination of two distinct monoclonal antibodies. These laboratory-engineered proteins were developed to assist the immune system in combating specific viral threats. The co-formulated product was designed for a particular purpose, which became prominent during the COVID-19 pandemic.
What Are Casirivimab and Imdevimab
Casirivimab and imdevimab are laboratory-made proteins, specifically a type of monoclonal antibody, that mimic the body’s natural immune response. Monoclonal antibodies are designed in a laboratory to target and neutralize specific pathogens, like viruses. Casirivimab (REGN10933) and imdevimab (REGN10987) were developed by Regeneron Pharmaceuticals.
These two antibodies are combined into a single co-formulated product, often referred to by the brand name REGEN-COV. They are intended to be administered together, either as an infusion or subcutaneous injection. This dual antibody approach is a strategy to help prevent the target virus from evolving and escaping the treatment.
How These Antibodies Work
Casirivimab and imdevimab function by targeting the spike protein of the SARS-CoV-2 virus, which is the virus responsible for COVID-19. The spike protein is a structure on the surface of the virus that allows it to attach to and enter human cells. By binding to non-overlapping regions of this spike protein, specifically the receptor-binding domain, the antibodies effectively block the virus’s ability to infect cells. This binding action neutralizes the virus, preventing it from spreading further within the body.
Their Role in COVID-19 Treatment
Casirivimab and imdevimab played a role in the early treatment strategies for the COVID-19 pandemic. They were primarily intended for treating mild-to-moderate COVID-19 in patients who were not hospitalized and who faced a high risk of their condition worsening to severe disease, requiring hospitalization, or leading to death. This included individuals with certain underlying health conditions or those over 65 years of age.
The U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for casirivimab and imdevimab in November 2020. This authorization allowed for their use in specific patient populations to help reduce the burden on healthcare systems by preventing hospitalizations.
Clinical trials showed that, when administered together, casirivimab and imdevimab reduced COVID-19-related hospitalizations or emergency room visits in high-risk individuals within 28 days of treatment, compared to a placebo. For instance, in high-risk patients, hospitalizations and emergency room visits occurred in approximately 3% of those treated with the antibodies, compared to about 9% in placebo-treated patients. The treatment was not authorized for patients who were already hospitalized due to COVID-19 or those requiring oxygen therapy, as studies did not show a benefit in these groups and, in some cases, monoclonal antibodies were associated with worse outcomes for hospitalized patients needing high-flow oxygen or mechanical ventilation.
Administering the Treatment and Who Was Eligible
The administration of casirivimab and imdevimab typically involved a healthcare professional in a monitored clinical setting. The primary method of delivery was intravenous (IV) infusion, where the medication was slowly dripped into a vein over a period, often between 20 to 50 minutes. In situations where IV infusion was not practical or would cause a delay in treatment, subcutaneous injections (under the skin) were an authorized alternative, given as multiple separate injections in areas like the abdomen, upper thighs, or upper arms.
Patients needed to be at least 12 years of age and weigh a minimum of 40 kilograms (approximately 88 pounds). A positive direct SARS-CoV-2 viral test result was also required. The therapy was reserved for non-hospitalized individuals who had mild-to-moderate COVID-19 symptoms but were at high risk for progressing to severe disease, hospitalization, or death. High-risk factors included being 65 years or older, or having certain chronic medical conditions such as obesity, chronic kidney disease, diabetes, or immunosuppression.
Potential Side Effects and Current Status
Casirivimab and imdevimab were associated with potential side effects. Common adverse reactions included injection site reactions such as pain, bleeding, bruising, soreness, swelling, or infection, particularly with subcutaneous administration. Infusion-related reactions were also observed, which could manifest as fever, chills, nausea, headache, dizziness, changes in heart rate, chest pain, or difficulty breathing. These reactions typically occurred during or within 24 hours of the infusion and were mostly moderate in severity, though severe or life-threatening hypersensitivity reactions, including anaphylaxis, were possible. Patients were monitored closely during and for at least an hour after administration.
The current status of casirivimab and imdevimab has changed since their initial authorization. Their emergency use authorization (EUA) by the FDA was revoked, and the product is no longer available for use in most regions. This change was primarily due to the emergence and widespread circulation of new SARS-CoV-2 variants, such as Omicron, against which casirivimab and imdevimab demonstrated significantly reduced activity. As a result of viral evolution, regulatory bodies determined that the known and potential benefits of the treatment no longer outweighed the known and potential risks for the currently circulating variants.