US FDA Authorizes Bamlanivimab, Etesevimab Monoclonal Antibodies For Treatment Of COVID-19

Maryland : The U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for bamlanivimab and etesevimab administered together for the treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age or older weighing at least 40 kilograms [about 88 pounds]) who test positive for SARS-CoV-2 and who are at high risk for progressing to severe COVID-19. The authorized use includes treatment for those who are 65 years of age or older or who have certain chronic medical conditions. The authorized dosage is bamlanivimab 700 mg and etesevimab 1400 mg administered together. Under this EUA, bamlanivimab and etesevimab must be diluted and administered together as a single intravenous (IV) infusion as soon as possible after positive viral test for SARS-CoV-2 and within 10 days of symptom onset.

Bamlanivimab and etesevimab are not authorized for use in patients who are hospitalized due to COVID-19, 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 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. Additional information regarding Limitations of Authorized Use can be found in the Fact Sheet for Health Care Providers linked below.

Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of bamlanivimab with and without etesevimab. Infusion-related reactions have been observed with administration of bamlanivimab and etesevimab together. These reactions may be severe or life threatening, warranting slowing or stopping the infusion and administering appropriate medications and/or supportive care. Additional information regarding these reactions can be found in the Fact Sheet for Health Care Providers linked below.

Bamlanivimab and etesevimab are monoclonal antibodies that are specifically directed against the spike protein of SARS-CoV-2, designed to block the virus’ attachment and entry into human cells. Bamlanivimab and etesevimab bind to different but overlapping sites on the spike protein of the virus. Using both antibodies together is expected to reduce the risk of viral resistance.

PK of bamlanivimab and etesevimab are linear and dose-proportional between 700 mg and 7000 mg following a single IV administration. There were no differences in PK of bamlanivimab between severe/moderate participants who were hospitalized and mild/moderate ambulatory participants. There were no differences in PK of etesevimab between mild/moderate ambulatory participants and healthy participants. There is no change in PK of bamlanivimab or etesevimab administered alone or together suggesting there is no interaction between the two antibodies.

Mean (90% CI) bamlanivimab Cmax was 196 µg/mL (102 to 378 µg/mL) following approximately 1 hr 700 mg IV infusion. Mean (90% CI) etesevimab Cmax is estimated to be 504 µg/mL (262 to 974 µg/mL) following approximately 1 hr 1400 mg IV infusion.

Bamlanivimab mean volume of distribution (Vd) was 2.87 L and 2.71 L for the central and peripheral compartments, respectively; the between subject variability (%CV) was 23.2%. Etesevimab mean Vd was 2.38 L and 1.98 L for the central and peripheral compartments, respectively; %CV was 27.8%.

Bamlanivimab and etesevimab are expected to be degraded into small peptides and component amino acids via catabolic pathways in the same manner as endogenous IgG antibodies. Bamlanivimab clearance (CL) was 0.27 L/hr (22.3%) and the mean apparent terminal elimination half-life was 17.6 days (15.8%). Etesevimab CL was 0.128 L/hr (33.8%) and the mean apparent terminal elimination half-life was 25.1 days (29.2%).

The PK profiles of bamlanivimab and etesevimab were not affected by age, sex, race, body weight (over the body weight range of 41 kg to 173 kg), or disease severity. Renal impairment is not expected to impact the PK of bamlanivimab and etesevimab. There is no significant difference in PK of bamlanivimab or etesevimab in patients with mild hepatic impairment compared to patients with normal hepatic function. Bamlanivimab and etesevimab have not been studied in patients with moderate or severe hepatic impairment.

The safety and effectiveness of bamlanivimab and etesevimab administered together are being assessed in adolescent patients in ongoing clinical trials. The recommended dosing regimen is expected to result in comparable serum exposures of bamlanivimab and etesevimab in patients 12 years of age and older and weighing at least 40 kg as observed in adults, based on a PK modeling approach which accounted for effect of body weight changes associated with age on clearance and volume of distribution.

In a clinical trial of patients with COVID-19 at high risk for disease progression, a single IV infusion of bamlanivimab 2800 mg and etesevimab 2800 mg administered together significantly reduced COVID-19-related hospitalization and death during 29 days of follow-up compared to placebo. The safety and effectiveness of this investigational therapy for use in the treatment of COVID-19 continue to be evaluated. Detailed information on the clinical trials and supporting data for this EUA can be found in the Fact Sheet for Health Care Providers linked below.

The authorized dosage of 700 mg bamlanivimab and 1400 mg etesevimab administered together is based on analyses of available preclinical, clinical, and virologic data, as well as PK and pharmacodynamic modeling, which, in totality, support that the authorized dosage is expected to have a similar clinical and virologic effect to 2800 mg bamlanivimab and 2800 mg etesevimab administered together.

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