REGEN-COV, developed by Regeneron, was an important early therapeutic option against COVID-19. This treatment is a monoclonal antibody cocktail, combining two distinct laboratory-made antibodies: casirivimab and imdevimab. It was authorized for emergency use to treat mild-to-moderate COVID-19 infection and prevent progression to severe disease, hospitalization, or death.
The Science Behind REGEN-COV
REGEN-COV utilizes two recombinant human monoclonal antibodies engineered to mimic the natural immune response. These components, casirivimab and imdevimab, were designed to specifically bind to the SARS-CoV-2 spike protein.
The spike protein is what the virus uses to attach to and enter human cells. Both antibodies attach to non-overlapping sites (epitopes) within the spike protein’s receptor-binding domain (RBD). By occupying these sites, the antibodies neutralize the virus, blocking viral entry into the host cell.
The treatment was formulated as a cocktail of two antibodies to reduce the chance of the virus developing resistance, known as viral escape. If a mutation allowed the virus to evade one antibody, the second would still be present to neutralize the threat. This two-pronged mechanism maintained effectiveness even as the virus evolved.
Clinical Use and Patient Eligibility
Under the Emergency Use Authorization (EUA) granted by the FDA, REGEN-COV had two main indications. The primary use was treating mild-to-moderate COVID-19 in patients who tested positive and were considered high-risk for progression to severe disease.
The second authorized use was post-exposure prophylaxis, preventing the disease in high-risk individuals exposed to COVID-19. For maximum effectiveness, it had to be administered quickly following a positive test, typically within ten days of symptom onset. This timing is crucial because monoclonal antibodies are most beneficial before the virus has replicated extensively.
REGEN-COV required administration via either an intravenous (IV) infusion or a subcutaneous (SC) injection. While IV infusion was generally preferred, SC injection was authorized as an alternative when IV access was difficult or caused significant treatment delays. Patients were monitored for at least an hour after receiving the medication to watch for immediate reactions.
The treatment was generally well-tolerated but carried the potential for side effects, including mild infusion-related reactions (hives, itching, flushing, or rash) and rare, severe allergic reactions like anaphylaxis. The authorization explicitly stated that REGEN-COV was not to be used in patients already hospitalized due to COVID-19 or requiring oxygen therapy.
Regulatory Status and Variant Resistance
The authorization for REGEN-COV was ultimately revoked due to the rapid evolution of the SARS-CoV-2 virus. Viral evolution produces new variants that often carry mutations on the spike protein targeted by the cocktail. These mutations can prevent the existing monoclonal antibodies from binding effectively.
Variant resistance became a significant problem with the emergence of the Omicron variant and its sublineages. Laboratory testing showed that the mutations on the Omicron spike protein dramatically reduced the binding affinity and neutralizing capability of casirivimab and imdevimab. The drug essentially lost potency against the dominant circulating strain.
In January 2022, the FDA revised the EUA for REGEN-COV, halting its use in the United States. This action occurred because the Omicron variant became the overwhelmingly dominant strain, accounting for over 99% of new infections. Continuing to use an ineffective treatment risked exposing patients to adverse effects without providing therapeutic benefit.
The regulatory decision was based on the determination that if a highly prevalent variant is resistant, the benefits of the drug no longer outweigh the risks. The authorization was officially withdrawn, and REGEN-COV is currently not authorized or recommended for use in most global regions where resistant variants remain dominant.