Bebtelovimab, alone or together with bamlanivimab and etesevimab, as a broadly neutralizing monoclonal antibody treatment for mild to moderate, ambulatory COVID-19

Abstract: medRxiv preprint doi: https://doi.org/10.1101/2022.03.10.22272100; this version posted March 12, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Bebtelovimab, alone or together with bamlanivimab and etesevimab, as a broadly neutralizing monoclonal antibody treatment for mild to moderate, ambulatory COVID-19. Authors: Michael Dougan, MD, PhD1; Masoud Azizad, MD2, Peter Chen, MD3; Barry Feldman, MD4; Matthew Frieman, PhD5; Awawu Igbinadolor, MD6; Princy Kumar, MD7; Jason Morris, MD8; Jeffrey Potts, MD9; Lauren Baracco, BS5; Lisa Macpherson, MSPHc10; Nicole L. Kallewaard, PhD10; Dipak R. Patel, MD, PhD10; Matthew M. Hufford, PhD10; Linda Wietecha, MSc10; Emmanuel Chigutsa, PhD10; Sarah L. Demmon, MS10; Bryan E. Jones, PhD10; Ajay Nirula, MD, PhD10; Daniel M. Skovronsky, MD, PhD10; Mark Williams, MD, FCCM, FCCP10; Robert L. Gottlieb, MD, PhD11. Affiliations: 1Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 2Valley Clinical Trials, Northridge, CA, USA; 3Cedars–Sinai Medical Center, Los Angeles, CA, USA; 4Millennium Medical Group, Farmington Hills, MI, USA; 5University of Maryland School of Medicine, Baltimore, MD; 6Monroe Biomedical Research, Monroe, NC, USA; 7Georgetown University, Washington, DC, USA; 8Clinical Trials of Southwest Louisiana, Lake Charles, LA, USA; 9Great Lakes Research Group, Inc., Bay City, MI, USA; 10Eli Lilly and Company, Indianapolis, IN, USA. 11Baylor University Medical Center and Baylor Scott & White Research Institute, Dallas, TX, USA; Corresponding author: Robert L. Gottlieb, MD, PhD, Baylor University Medical Center and Baylor Scott & White Research Institute, Dallas, TX, USA. E-mail: Robert.Gottlieb@BSWHealth.org. Phone: +1-214-820-6856 (Office). NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. 1 medRxiv preprint doi: https://doi.org/10.1101/2022.03.10.22272100; this version posted March 12, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . BACKGROUND: Bebtelovimab is a potent, fully human IgG1 monoclonal antibody (mAb) targeting the S-protein of SARS-CoV-2, with broad neutralizing activity to all currently known SARS-CoV-2 variants of concern, including omicron variant lineages. Specialized developmental approaches accelerated the initiation of a clinical trial designed to evaluate the efficacy and safety of bebtelovimab alone (BEB) or together with bamlanivimab (BAM) and etesevimab (ETE) delivered via slow intravenous push for the treatment of mild-tomoderate COVID-19. METHODS: This portion of the phase 2, BLAZE-4 trial (J2X-MC-PYAH; NCT04634409) enrolled 714 patients (between May and July 2021) with mild-to-moderate COVID-19 within 3 days (≤3 days) of laboratory diagnosis of SARS-CoV-2 infection. Patients at low risk for severe COVID19 were randomized 1:1:1 (double-blinded) to placebo, BEB 175 mg, or BEB 175 mg+BAM 700 mg+ETE 1400 mg (BEB+BAM+ETE). Patients at high risk for progression to severe COVID-19 were randomized 2:1 (open-label) to BEB or BEB+BAM+ETE, and a subsequent treatment arm enrolled..