The U.S. Food and Drug Administration (FDA) has revoked the emergency use authorization (EUA) for bamlanivimab when used as a monotherapy for the treatment of mild-to-moderate COVID-19 in adults and certain pediatric patients. This decision, announced on April 16, 2021, was based on the agency's analysis of emerging scientific data indicating a sustained increase in SARS-CoV-2 viral variants resistant to bamlanivimab alone, leading to a higher risk of treatment failure.
Increasing Variant Resistance
Recent data from the U.S. Centers for Disease Control and Prevention's (CDC) national genomic surveillance program revealed a significant rise in the frequency of SARS-CoV-2 variants expected to be resistant to bamlanivimab monotherapy. As of mid-March 2021, approximately 20% of viruses sequenced in the U.S. were reported as variants with expected resistance, a substantial increase from approximately 5% in mid-January 2021. This rapid shift in viral strains prompted the FDA to reassess the risk-benefit profile of bamlanivimab monotherapy.
Impact on Treatment
The FDA's decision means that bamlanivimab, when administered alone, is no longer considered an appropriate treatment option for COVID-19 due to the increased likelihood of treatment failure. According to Patrizia Cavazzoni, M.D., Director of the FDA's Center for Drug Evaluation and Research, "While the risk-benefit assessment for using bamlanivimab alone is no longer favorable due to the increased frequency of resistant variants, other monoclonal antibody therapies authorized for emergency use remain appropriate treatment choices...and can help keep high risk patients with COVID-19 out of the hospital."
Alternative Monoclonal Antibody Therapies
Despite the revocation of the EUA for bamlanivimab monotherapy, the FDA emphasizes that alternative monoclonal antibody therapies remain available under EUA. These include REGEN-COV (casirivimab and imdevimab, administered together) and bamlanivimab and etesevimab, administered together. These alternative therapies are authorized for the same uses as previously authorized for bamlanivimab alone, targeting mild-to-moderate COVID-19 in high-risk individuals.
Monoclonal Antibodies and Viral Mutation
Monoclonal antibodies are laboratory-made proteins designed to mimic the immune system's ability to combat harmful pathogens, including viruses like SARS-CoV-2. However, like other infectious organisms, SARS-CoV-2 can mutate over time, resulting in genetic variation in circulating viral strains. This genetic variation can lead to the emergence of variants that are less susceptible to specific monoclonal antibody therapies.
Ensuring Effective Treatment
The FDA highlights the absence of readily available testing technologies to identify SARS-CoV-2 viral variants in individual patients before initiating monoclonal antibody treatment. Consequently, the agency recommends using monoclonal antibody therapies expected to work broadly against all variants across the nation to reduce the likelihood of treatment failure. The FDA continues to collaborate with the CDC and the National Institutes of Health to monitor variants and their impact on authorized monoclonal antibody therapies, ensuring timely and transparent communication as new information emerges.
