FDA Issues EUA for Monoclonal Antibodies as Treatment for COVID-19
A clinical trial of patients with COVID-19 at high risk for disease progression showed that a single intravenous infusion of bamlanivimab and etesevimab together significantly reduce COVID-19-related hospitalization and death.
Officials with the FDA have issued an emergency use authorization (EUA) for Eli Lilly and Co.’s investigational bamlanivimab (LY-CoV555) and etesevimab (LY-CoV016) administered together for the treatment of mild to moderate cases of the coronavirus disease 2019 (COVID-19). The EUA is indicated for adults and pediatric patients (ages 12 years or older weighing at least 40 kilograms [about 88 pounds]) who test positive for SARS-CoV-2, the virus that causes COVID-19, and who are at high risk for progressing to severe COVID-19.
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.
According to the FDA, a clinical trial of patients with COVID-19 at high risk for disease progression showed that a single intravenous infusion of bamlanivimab and etesevimab administered together significantly reduce 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.
The data supporting the EUA for bamlanivimab and etesevimab are based on a randomized, double-blind, placebo-controlled clinical trial in 1035 nonhospitalized adults with mild to moderate COVID-19 symptoms who were at high risk for progressing to severe COVID-19. Of these patients, 518 received a single infusion of bamlanivimab 2800 milligrams and etesevimab 2800 milligrams together, and 517 received placebo. The primary endpoint was COVID-19 related hospitalizations or death by any cause during 29 days of follow-up. Hospitalization or death occurred in 7% of patients who received placebo compared to 2% of patients treated with bamlanivimab 2800 milligrams and etesevimab 2800 milligrams administered together, a 70% reduction. All 10 deaths occurred in the placebo group. Thus, all-cause death was significantly lower in the bamlanivimab 2800-milligram and etesevimab 2800-milligram group than the placebo group.
The authorized dosage of 700 milligrams bamlanivimab and 1400 milligrams etesevimab administered together is based on analyses of available preclinical, clinical, and virologic data, as well as pharmacokinetic and pharmacodynamic modeling, which, in totality, support that the authorized dosage is expected to have a similar clinical and virologic effect to 2800 milligrams bamlanivimab and 2800 milligrams etesevimab administered together.
On Nov. 9, 2020, the FDA issued an EUA for a single infusion of 700 mg bamlanivimab for the treatment of mild-to-moderate COVID-19 in adult and certain pediatric patients. While bamlanivimab and etesevimab administered together resulted in a lower risk of resistant viruses developing during treatment compared with bamlanivimab administered alone, both treatments are expected to benefit patients at high risk of disease progression. At present, both 700 milligrams bamlanivimab alone as well as 700 milligrams bamlanivimab and 1,400 milligrams etesevimab administered together will be available under an EUA.
Serious and unexpected adverse events including hypersensitivity, anaphylaxis, and infusion-related reactions have been observed with bamlanivimab with and without coadministration of etesevimab. In addition, clinical worsening following bamlanivimab administration has been reported, although it is not known if these events were related to bamlanivimab use or were due to progression of COVID-19. Possible adverse effects of bamlanivimab and etesevimab administered together include nausea, dizziness, pruritus, and rash.
Bamlanivimab and etesevimab are not authorized for patients who are hospitalized due to COVID-19 or require oxygen therapy due to 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.
Coronavirus (COVID-19) Update: FDA Authorizes Monoclonal Antibodies for Treatment of COVID-19 [news release]. Silver Spring, MD; February 9, 2021: FDA.