Etesevimab

An anti-Spike (SARS-CoV-2) monoclonal antibody.

Phase of research

Emergency use authorization

How it helps

Antiviral

Drug status

Experimental

2
Supporting references
11
Contradictory references
9
Clinical trials

General information

Etesevimab is a human recombinant monoclonal antibody targeting SARS-CoV-2 Spike protein RBD. It blocks the interaction between viral Spike and the host’s ACE2 receptor and is therefore investigated in COVID-19 treatment (DrugBank).

On February 9, 2021, the FDA issued an Emergency Use Authorization for emergency use of bamlanivimab and etesevimab 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 are neutralizing IgG1 monoclonal antibodies that bind to distinct but overlapping epitopes within the receptor binding domain of the spike protein of SARS-CoV-2. They are both
investigational drugs and are not currently approved for any indication.

 


Synonyms

LY3832479; LY-CoV016; JS016; CB6


Supporting references

Link Tested on Impact factor Notes Publication date DB entry date
Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum
Antibody Biophysical assay Crystallization DNA In vitro Mixed substance Protein factor RNA Spike protein Spike variant
in vitro biophysical assay; crystallization; sera of COVID-19 convalescent patients and vaccinated adults; Vero cells; HEK293T/17-hACE2 cells; SARS-CoV-2 (Victoria, Alpha, Beta, and Delta); (HIV-1) SARS-CoV-2 Spike-pseudotyped virus (various variants) 41.58 (2020)

The antibody neutralized the Delta variant of SARS-CoV-2 in vitro. 

Jun/17/2021 Mar/11/2022
Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19
Antibody Mild severity Moderate severity Randomized controlled double-blind trial Spike protein Phase II clinical trial
Mild to moderate COVID-19 outpatients. 45.54

Etesevimab therapy in combination with bamlanivimab in mild to moderate COVID-19 patients was associated with statistically significant decrease in viral load compared to placebo.

Jan/21/2021 Jan/24/2021

Contradictory references

Link Tested on Impact factor Notes Publication date DB entry date
Efficacy of Antibodies and Antiviral Drugs against Covid-19 Omicron Variant
Spike protein Spike variant Protein factor In vitro Antibody
Vero E6-TMPRSS2 cells; SARS-CoV-2 strains (SARS-CoV-2/UT-NC002-1T/Human/2020/Tokyo, alpha, beta, gamma, delta, omicron) 91.25 (2020)

The antibody did not neutralize beta, gamma, and omicron strains of SARS-CoV-2 in vitro. 

Jan/26/2022 Feb/22/2022
A non-ACE2-blocking neutralizing antibody against Omicron-included SARS-CoV-2 variants
ACE2 Animal model Antibody Cryo-EM In vitro Mechanism Protein factor Spike protein Spike variant
Huh-7 cells; hACE2 mice; (VSV) SARS-CoV-2 Spike-pseudotyped virus (various strains) 18.19 (2020)

A significant loss of binding affinity of the antibody to Omicron SARS-CoV-2 Spike RBD was observed in vitro. 

Jan/25/2022 Feb/22/2022
Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement
Antibody Biophysical assay Cryo-EM Crystallization In vitro Protein factor Spike protein Spike variant
In vitro 47.73 (2020)

The antibody had no affinity for B.1.1.529 (Omicron) variant Spike of SARS-CoV-2 in vitro. 

Jan/25/2022 Feb/18/2022
An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies
Spike protein Spike variant Protein factor In vitro Antibody
Vero-TMPRSS2 cells; Vero-hACE2-TMPRSS2 cells; SARS-CoV-2 strains WA1/2020 and hCoV-19/USA/WI-WSLH-221686/2021 (Omicron) 53.44 (2020)

The antibody failed to neutralize B.1.1.529 (Omicron) variant of SARS-CoV-2 in vitro. 

Jan/19/2022 Feb/18/2022
SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses
ACE2 Antibody Biophysical assay Crystallization DNA In vitro Mixed substance Protein factor RNA Spike protein Spike variant
sera from vaccinated or convalescent individuals; VeroE6/TMPRSS2 cells; SARS-CoV-2 (various strains) 41.58 (2020)

Does not neutralize the omicron variant of SARS-CoV-2 in vitro. 

Jan/04/2022 Mar/07/2022
Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies
Spike protein Spike variant Protein factor In vitro Antibody Screening
Huh-7 cells; SARS-CoV-2 Spike-pseudotyped viruses (various strains/mutations) 49.96 (2020)

The antibody was inefficient in Omicrom (SARS-Cov-2) neutralization in vitro. 

Dec/23/2021 Feb/22/2022
The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic
Spike protein Spike variant Protein factor Viral vector In vitro Antibody
293T cells; A549-ACE2 cells; BHK-21 cells; Vero cells; Huh-7 cells; Calu-3 cells; Caco-2 cells; (VSV) SARS-CoV-2 Spike pseudoviruses (B.1, Alpha, Beta, Gamma, Delta, or Omicron) 41.58 (2020)

Alone or in combination with Bamlanivimab, the antibody did not neutralize Omicron variant and did not inhibit Spike-mediated cell entry in vitro. 

Dec/23/2021 Feb/18/2022
Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift
Spike protein Spike variant Protein factor In vitro Antibody
Vero E6-TMPRSS2 cells; SARS-CoV-2 Spike-pseudotyped viruses (including WA1/2020 D614G or Omicron) 49.96 (2020)

Lost its neutralization potency against Omicron variant of SARS-CoV-2 in vitro. 

Dec/23/2021 Feb/18/2022
Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016
Spike protein In vitro Antibody
in vitro binding assay N/A (new)

Several mutations, including those found in emerging SARS-CoV-2 variants (P.1 or B.1.351.), were shown to facilitate viral escape from the antibody. For some single mutations or some doble mutations present in certain emergent viral strains, viral escape from the antibody in a cocktail with bamlanivimab is possible, as well.

Apr/01/2021 May/02/2021
Antibody evasion by the P.1 strain of SARS-CoV-2
Antibody Biophysical assay Crystallization DNA In vitro Mixed substance Protein factor RNA Spike protein Spike variant
in vitro biophysical assay; crystallization; sera of COVID-19 convalescent patients and vaccinated adults; Vero cells; SARS-CoV-2 (Victoria, Alpha, Beta, and Gamma) 41.58 (2020)

A severe loss in neutralization potency against Beta and Gamma strains of SARS-CoV-2 was observed. 

Mar/30/2021 Mar/11/2022
Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7
Spike protein Spike variant Protein factor In vitro Antibody Mixed substance
Vero E6 cells; patient sera; SARS-CoV-2 live virus (WA1, B.1.1.7, and B.1.351 strains); (VSV) SARS-CoV-2 Spike pseudoviruses (various strain/mutations) 49.96 (2020)

Etesevimab in combination with Bamlanivimab is not active against B.1.351 in vitro. 

Mar/08/2021 Feb/18/2022

Clinical trials

ID Title Status Phase Start date Completion date
NCT05167279 A Study of JS026 and JS026 Together With JS016 for Treatment of COVID-19 Active, not recruiting Phase 1 Dec/17/2021 Dec/31/2022
NCT05205759 Non-inferiority Trial on Monoclonal Antibodies in COVID-19 Recruiting Phase 3 Dec/09/2021 Jul/01/2022
NCT05268601 COVID-19 and Disease Progression to the Severe Form: A Study on the Use of Monoclonal Antibodies Against SARS-CoV-2 Recruiting Oct/14/2021 May/31/2024
NCT04790786 UPMC OPTIMISE-C19 Trial, a COVID-19 Study Recruiting Phase 3 Mar/10/2021 Dec/01/2023
NCT04931238 Efficacy and Safety of JS016 in Patients With SARS-CoV-2 Infection (COVID-19) Recruiting Phase 2 Jan/20/2021 Dec/31/2022
NCT04634409 A Study of Immune System Proteins in Participants With Mild to Moderate COVID-19 Illness Completed Phase 2 Oct/29/2020 Oct/20/2021
NCT04497987 A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Preventing SARS-CoV-2 Infection and COVID-19 in Nursing Home Residents and Staff Completed Phase 3 Aug/02/2020 May/20/2021
NCT04427501 A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Participants With Mild to Moderate COVID-19 Illness Completed Phase 2|Phase 3 Jun/17/2020 Dec/14/2021
NCT04441918 Tolerability,Safety,Pharmacokinetic Profile and Immunogenicity of a Recombinant Humanized Anti-SARS-CoV-2 Monoclonal Antibody (JS016) for Injection in Chinese Health Subjects Recruiting Phase 1 Jun/05/2020 Dec/11/2020