Bamlanivimab emerged as a therapeutic agent during the early phases of the COVID-19 pandemic. This monoclonal antibody was developed to treat the SARS-CoV-2 virus. Its purpose was to help individuals with mild to moderate COVID-19 avoid progression to severe illness, including hospitalization.
How Bamlanivimab Works
Bamlanivimab functions as a monoclonal antibody, a type of laboratory-made protein designed to mimic the immune system’s natural ability to fight off foreign invaders. This specific antibody was engineered to target the spike protein of the SARS-CoV-2 virus. The spike protein is a projection on the virus’s surface that allows it to attach to and enter human cells.
The antibody binds to a particular region on the spike protein called the receptor-binding domain (RBD). This RBD is responsible for interacting with the human angiotensin-converting enzyme 2 (ACE2) receptor, which acts as the entry point for the virus into host cells. By binding to the RBD, bamlanivimab physically blocks the spike protein from attaching to the ACE2 receptor. This prevents the virus from entering and replicating within human cells, thereby neutralizing its ability to cause infection.
Its Role in COVID-19 Treatment
Bamlanivimab was authorized for emergency use to treat individuals with mild to moderate COVID-19. Eligibility included adults and pediatric patients aged 12 years and older, weighing at least 40 kilograms, who tested positive for SARS-CoV-2 and were at high risk for progressing to severe COVID-19. High-risk factors included age 65 or older, or age 55 or older with conditions such as cardiovascular disease, hypertension, or chronic respiratory disease. Other qualifying conditions included a body mass index (BMI) of 35 or higher, chronic kidney disease, diabetes, or immunosuppressive conditions.
The therapy was administered as a single dose via intravenous infusion. Treatment was important to occur as soon as possible after a positive viral test and within 10 days of symptom onset. Bamlanivimab was not authorized for patients hospitalized due to COVID-19 or who required oxygen therapy, as studies did not show a benefit in these severe cases.
Why Its Use Was Limited or Discontinued
The utility of bamlanivimab as a standalone treatment diminished with the emergence of new SARS-CoV-2 variants. As the virus evolved, mutations appeared in the spike protein, particularly within the receptor-binding domain that bamlanivimab targeted. These mutations reduced the antibody’s ability to bind effectively to the altered spike protein.
By mid-March 2021, approximately 20% of sequenced viruses in the U.S. were variants expected to be resistant to bamlanivimab alone, a significant increase from about 5% in mid-January 2021. This increase in resistant variants led the U.S. Food and Drug Administration (FDA) to determine that the benefits of bamlanivimab, when administered alone, no longer outweighed the risks for its authorized use. Consequently, the FDA revoked its Emergency Use Authorization (EUA) for bamlanivimab monotherapy in April 2021.
This revocation was a direct result of the evolving variant landscape, as the drug became less effective against circulating strains. The focus shifted towards other monoclonal antibody therapies, or combinations of antibodies, that retained efficacy against newer variants. For instance, the combination of bamlanivimab and etesevimab neutralized more of the emerging variants. The manufacturer, Eli Lilly and Company, requested the revocation of the EUA for bamlanivimab alone due to variant resistance and the availability of the combined therapy.