The Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for bebtelovimab for the treatment of mild to moderate COVID-19 in patients 12 years of age and older weighing at least 40kg with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options approved or authorized by the FDA are not accessible or clinically appropriate.
Bebtelovimab is a recombinant neutralizing human IgG1κ monoclonal antibody that works by binding to the spike protein of SARS-CoV-2. The EUA was supported by data from the phase 2 BLAZE-4 trial (ClinicalTrials.gov Identifier: NCT04634409), which evaluated the efficacy and safety of bebtelovimab in nonhospitalized patients with mild to moderate COVID-19. Patients received a single IV infusion of bebtelovimab 175mg alone or together with bamlanivimab 700mg and etesevimab 1400mg.
Among 380 low-risk patients enrolled in the placebo-controlled portion of the trial, treatment with bebtelovimab resulted in a reduction in time to sustained symptom resolution compared with placebo. The median time to sustained symptom resolution was 7 days (95% CI, 6-8) for patients treated with bamlanivimab, etesevimab, and bebtelovimab together (P =.289) and 6 days (95% CI, 5-7) for patients treated with bebtelovimab alone (P =.003), compared with 8 days (95% CI, 7-9) for patients treated with placebo. There was also a reduction in viral load observed on day 5 after treatment compared with placebo.
In the randomized, open-label portion of the trial, 150 high-risk patients were treated with a single infusion of bebtelovimab alone or together with etesevimab and bamlanivimab. The proportion of patients with COVID-19 related hospitalization or death by any cause was assessed by day 29. Results showed events occurred in 2 patients treated with the combination of bamlanivimab, etesevimab, and bebtelovimab and in 3 patients treated with bebtelovimab alone. One patient treated with bebtelovimab alone died on day 34. The median time to sustained symptom resolution was 7 days for patients treated with bebtelovimab alone.
In the nonrandomized, open-label portion of the trial, 176 high-risk patients were treated with a single infusion of bamlanivimab, etesevimab, and bebtelovimab. The proportion of patients with COVID-19 related hospitalization or death by any cause was assessed by day 29. Events occurred in 3 patients with no deaths reported. The median time to sustained symptom resolution was 8 days.
BLAZE-4 was conducted prior to the emergence of the Omicron variant; no patients in the study were infected with virus of the Omicron lineage or sublineages. However, nonclinical viral neutralization data showed that bebtelovimab retained full neutralizing activity against Omicron and all other known variants of interest and concern, including BA.2.
The most common adverse reactions reported with bebtelovimab were infusion-related reactions (0.3%), pruritus (0.3%), and rash (0.8%). Treatment with bebtelovimab may also be associated with serious hypersensitivity reactions, including anaphylaxis.
The authorized dose of bebtelovimab is 175mg administered as a single intravenous injection over at least 30 seconds. Bebtelovimab should be administered as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 7 days of symptom onset. The product is supplied as a 175mg/2mL single-dose vial.
The health care provider fact sheet for bebtelovimab can be found here.
- Lilly’s bebtelovimab receives Emergency Use Authorization for the treatment of mild-to-moderate COVID-19. News release. Eli Lilly and Company. February 11, 2022. Accessed February 14, 2022. https://www.prnewswire.com/news-releases/lillys-bebtelovimab-receives-emergency-use-authorization-for-the-treatment-of-mild-to-moderate-covid-19-301480923.html
- Coronavirus (COVID-19) update: FDA authorizes new monoclonal antibody for treatment of COVID-19 that retains activity against Omicron variant. News release. US Food and Drug Administration. February 11, 2022. Accessed February 14, 2022. https://www.prnewswire.com/news-releases/coronavirus-covid-19-update-fda-authorizes-new-monoclonal-antibody-for-treatment-of-covid-19-that-retains-activity-against-omicron-variant-301480912.html
- AbCellera-discovered antibody, bebtelovimab, receives U.S. FDA Emergency Use Authorization for the treatment of mild-to-moderate COVID-19. News release. AbCellera. February 11, 2022. Accessed February 14, 2022. https://www.businesswire.com/news/home/20220211005524/en/AbCellera-Discovered-Antibody-Bebtelovimab-Receives-U.S.-FDA-Emergency-Use-Authorization-for-the-Treatment-of-Mild-to-Moderate-COVID-19
- Bebtelovimab fact sheet for health care providers. Accessed February 14, 2022. http://pi.lilly.com/eua/bebtelovimab-eua-factsheet-hcp.pdf