The Centers for Disease Control and Prevention (CDC) has identified that the combined frequencies of the SARS-CoV-2 P.1/Gamma variant (first identified in Brazil) and the B.1.351/Beta variant (first identified in South Africa) throughout the United States exceed 11% and are trending upward (https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-proportions.html).
Data suggests that bamlanivimab and etesevimab together are not active against either the P.1 (Gamma) or B.1.351 (Beta) variants, while other authorized monoclonal antibody therapies are expected to retain activity to this variant. Antiviral resistance information for bamlanivimab and etesevimab together can be found in Section 15 of the authorized Fact Sheet for Healthcare Providers. The FDA recommends that healthcare providers use alternative authorized monoclonal antibody therapies until further notice, and the Assistant Secretary for Preparedness and Response (ASPR) will temporarily stop shipping bamlanivimab and etesevimab together, and etesevimab alone to pair with existing bamlanivimab. You can read the Dear HCP Letter, or get more information on this and other updates here.
For additional information, contact the Lilly COVID Hotline at 1-855-545-5921 or visit LillyAntibody.com.
Bamlanivimab and etesevimab are authorized to be administered together for the treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progressing to severe COVID-19 and/or hospitalization.
- Bamlanivimab and etesevimab together have not been approved, but have been authorized for emergency use by the FDA.
- Bamlanivimab and etesevimab together are authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of bamlanivimab and etesevimab under Section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.
Limitations of Authorized Use
Bamlanivimab and etesevimab together are not authorized for use in patients:
- who are hospitalized due to COVID-19, OR
- who require oxygen therapy due to COVID-19, OR
- who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity.
- Treatment with bamlanivimab and etesevimab together has not been studied in patients hospitalized due to COVID-19. Monoclonal antibodies, such as bamlanivimab and etesevimab, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation.
IMPORTANT SAFETY INFORMATION
There are limited clinical data available for bamlanivimab and etesevimab. Serious and unexpected adverse events may occur that have not been previously reported with the use of bamlanivimab and etesevimab together.
Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions
Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of bamlanivimab with and without etesevimab. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive therapy.
Infusion-related reactions have been observed with administration of bamlanivimab and etesevimab together. These reactions may be severe or life threatening. Signs and symptoms of infusion-related reactions may include:
- fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia (e.g. atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, nausea, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, dizziness, and diaphoresis.
If an infusion-related reaction occurs, consider slowing or stopping the infusion and administer appropriate medications and/or supportive care.
Clinical Worsening After Bamlanivimab Administration
Clinical worsening of COVID-19 after administration of bamlanivimab has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmia (e.g., atrial fibrillation, sinus tachycardia, bradycardia), fatigue, and altered mental status. Some of these events required hospitalization. It is not known if these events were related to bamlanivimab use or were due to progression of COVID-19.
Limitations of Benefit and Potential Risk in Patients with Severe COVID-19
Treatment with bamlanivimab and etesevimab has not been studied in patients hospitalized due to COVID-19. Monoclonal antibodies, such as bamlanivimab and etesevimab, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation. See Limitations of Authorized Use.
Adverse reactions observed in those who have received bamlanivimab and etesevimab are anaphylaxis (n=1, 0.07%) and infusion-related reactions (n=16, 1.1%). The most common treatment-emergent adverse events included nausea, dizziness, and pruritis. No treatment-emergent events occurred in more than 1% of participants and rates were comparable to placebo.
USE IN SPECIFIC POPULATIONS
There are insufficient data to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Bamlanivimab and etesevimab should only be used during pregnancy if the potential benefit outweighs the potential risk for the mother and the fetus.
There are no available data on the presence of bamlanivimab or etesevimab in human or animal milk, the effects on the breastfed infant, or the effects on milk production. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.
Healthcare providers should review the Fact Sheet for Healthcare Providers for information on the authorized use of bamlanivimab and etesevimab and mandatory requirements of the EUA. Please also see the FDA Letter of Authorization and the Fact Sheet for Patients, Parents and Caregivers on the authorized use of bamlanivimab and etesevimab.