REGEN-COV was a therapy developed by Regeneron Pharmaceuticals composed of two monoclonal antibodies, casirivimab and imdevimab, administered together. The primary purpose of this combination treatment was to treat mild to moderate cases of COVID-19 and to prevent infection after a known exposure. The therapy was created to provide a form of immediate, passive immunity against the SARS-CoV-2 virus.
How REGEN-COV Works
The treatment’s two laboratory-made proteins mimic the antibodies produced by the human immune system in response to an infection. The antibodies, casirivimab and imdevimab, were specifically developed to target the spike protein of the SARS-CoV-2 virus, which the virus uses to enter human cells.
The two antibodies in REGEN-COV attach to two distinct, non-overlapping locations on the spike protein. This dual-binding action blocks the virus from latching onto and entering host cells. This mechanism was intended to halt viral replication, reduce the amount of virus in a person’s system, lessen symptom severity, and decrease the chances of severe disease progression.
Authorized Use and Administration
Under its Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA), REGEN-COV was intended for specific populations. The primary group eligible for treatment included adults and pediatric patients aged 12 and older with positive SARS-CoV-2 tests, mild to moderate symptoms, and who were at high risk for progressing to severe COVID-19. The therapy was not authorized for patients already hospitalized due to COVID-19.
The treatment was also authorized as post-exposure prophylaxis to prevent infection in high-risk individuals after exposure. The authorized dose was 600 mg of casirivimab and 600 mg of imdevimab, administered together as a single intravenous (IV) infusion, with subcutaneous injections as an alternative.
Clinical Efficacy and Variant Limitations
Initial clinical trials demonstrated that the antibody combination was effective against earlier strains of the SARS-CoV-2 virus. The treatment could reduce the risk of death in certain hospitalized patients who had not yet produced their own antibodies. For non-hospitalized patients with mild to moderate symptoms, data indicated that REGEN-COV reduced viral load and lowered the risk of hospitalization or death. This efficacy was most pronounced in patients who were seronegative, meaning their own immune systems had not yet mounted a response.
The effectiveness of REGEN-COV diminished with the evolution of the SARS-CoV-2 virus. The emergence of the Omicron variant revealed that specific mutations on its spike protein altered the binding sites for casirivimab and imdevimab. As Omicron and its subvariants became the dominant circulating strains, the utility of REGEN-COV was limited because it was no longer able to counter the prevalent form of the virus.
Current Status of Authorization
Due to its reduced effectiveness against the Omicron variant, the FDA revised the EUA for REGEN-COV in January 2022. The treatment was no longer authorized for use in any U.S. state or territory. The decision was based on data showing that the therapy was not expected to work against the then-dominant Omicron variant.
REGEN-COV is not currently a recommended or available treatment for COVID-19 in the United States. In late 2022, Regeneron requested that the FDA formally revoke the EUA, noting that all manufactured lots had expired and the company did not plan to offer the product in the U.S. going forward.
Potential Side Effects
The most common side effects were infusion-related reactions. These could include:
- Fever
- Chills
- Nausea
- Headache
Reactions at the injection site like bruising, soreness, or swelling were possible with subcutaneous injections. Allergic reactions were also a noted risk, such as rashes or hives. Although rare, more severe allergic reactions, including anaphylaxis, were a possibility with any infusion or injection. Individuals with a known history of a severe allergic reaction to the antibody cocktail were advised not to receive it.