Bamlanivimab

A potent anti-Spike (SARS-CoV-2) neutralizing monoclonal antibody.

Phase of research

Emergency use authorization

How it helps

Antiviral

Drug status

Experimental

4
Supporting references
12
Contradictory references
12
Clinical trials

General information

LY-CoV555 (also known as Bamlanivimab or LY3819253), a potent antispike neutralizing monoclonal antibody that binds with high affinity to the receptor-binding domain of SARS-CoV-2, was derived from convalescent plasma obtained from a patient with COVID-19 (Jones et al., 2021). The antibody was developed by Eli Lilly after its discovery by researchers at AbCellera and at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases. 

On November 9, 2020, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for the investigational monoclonal antibody therapy bamlanivimab for the treatment of mild-to-moderate COVID-19 in adult and pediatric patients. Bamlanivimab is authorized for patients with positive results of direct SARS-CoV-2 viral testing who are 12 years of age and older weighing at least 40 kilograms (about 88 pounds), and who are at high risk for progressing to severe COVID-19 and/or hospitalization. This includes those who are 65 years of age or older, or who have certain chronic medical conditions.

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

LY-CoV555


Marketed as

BAMLANIVIMAB


Supporting references

Link Tested on Impact factor Notes Publication date DB entry date
The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in non-human primates
Antibody Animal model Biophysical assay Cryo-EM Crystallization In vitro Spike protein
in vitro binding assay; in vitro biophysical assay; cryo-EM; crystallization; Vero E6 cells; rhesus macaque; SARS-CoV-2 Spike-pseudotyped virus; SARS-CoV-2 INMI-1 and USA/WA-1/2020 isolates 16.30

The antibody potently bound SARS-CoV-2 Spike RBD, inhibited its interaction with host ACE2, and displayed neutralizing activity in vitro. In a cynomolgus monkey viral challenge, a reduction of viral replication in respiratory tract was observed in the case of prophylactic dosing.

Apr/05/2021 Nov/10/2020
Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity
Antibody Biophysical assay Crystallization In silico In vitro Protein factor Spike protein Spike variant
Vero E6 cells; Vero E6-hACE2(-TMPRSS2) cells; (VSV) SARS-CoV-2 Spike-pseudotyped virus 41.58 (2020)

The antibody neutralized Spike (also N439K/K417V)-pseudotyped SARS-CoV-2 in vitro. 

Mar/04/2021 Feb/22/2022
Bamlanivimab for treatment of COVID‐19 in solid organ transplant recipients: Early single‐center experience
Spike protein Case series Antibody
Solid organ transplant recipients with COVID-19. 1.67

None of the mild to moderate COVID-19 patients, who were solid organ transplant recipients (liver or/and kidney or heart), experienced symptom worsening or required hospitalization.

Feb/17/2021 Feb/26/2021
SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19
Outpatients Antibody Moderate severity Mild severity
Patients 74.70

one of three doses of neutralizing antibody LY-CoV555 appeared to accelerate the natural decline in viral load over time, whereas the other doses had not by day 11

Oct/28/2020 Nov/10/2020

Contradictory references

Link Tested on Impact factor Notes Publication date DB entry date
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
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 Etesevimab, 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
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 failed to neutralize the Delta variant of SARS-CoV-2 in vitro. 

Jun/17/2021 Mar/11/2022
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 Etesevimab 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 complete loss of neutralization of Beta and Gamma strains of SARS-CoV-2 was observed. 

Mar/30/2021 Mar/11/2022
SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies
Antibody In vitro Mixed substance Peptide RNA Small molecule Spike protein
Caco-2 cells; Vero cells; Sera of vaccinated individuals; (VSV) SARS-CoV-2 Spike-pseudotyped virus (WT, B.1.1.7, B.1.351, ant P.1 variants) 38.64

Bamlanivimab displayed in vitro inhibition of SARS-CoV-2 Spike B.1.1.7-pseudotyped virus infection, but the emergent B.1.351 and P.1 were resistant to neutralization.

Mar/20/2021 Apr/05/2021
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)

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

Mar/08/2021 Feb/18/2022
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

Bamlanivimab monotherapy was not associated with significant change in viral load in mild to moderate COVID-19 patients compared to placebo. Sample size: 100 (0.7 g bamlanivimab) + 103 (2.8 g bamlanivimab) + 95 (7 g bamlanivimab) + 146 placebo. Dosage: 0.7 g or 2.8 g or 7 g. Endpoint: Change in SARS-CoV-2 log viral load at day 11.



Jan/21/2021 Jan/24/2021
A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19
Spike protein Randomized controlled double-blind trial Antibody
Hospitalized patients 74.70

Administered in combination with remdesivir. No improvement in clinical outcome compared to placebo. Sample size: 161 + 150 placebo (with outcomes). Dosage: 7 g in a single infusion. Endpoint: Time to a sustained recovery during a 90-day period (primary).



Dec/22/2020 Jan/07/2021

Clinical trials

ID Title Status Phase Start date Completion date
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
NCT04796402 A Study to Assess if a Medicine Called Bamlanivimab is Safe and Effective in Reducing Hospitalization Due to COVID-19 Active, not recruiting Phase 4 Mar/17/2021 Dec/31/2021
NCT04790786 UPMC OPTIMISE-C19 Trial, a COVID-19 Study Recruiting Phase 3 Mar/10/2021 Dec/01/2023
NCT04701658 A Real World Study of Bamlanivimab in Participants With Mild-to-Moderate Coronavirus Disease 2019 (COVID-19) Completed Phase 2 Feb/01/2021 Jun/22/2021
NCT04656691 At-Home Infusion Using Bamlanivimab in Participants With Mild to Moderate COVID-19 Terminated Phase 4 Jan/04/2021 Apr/18/2021
NCT04840459 Use of Monoclonal Antibodies for the Treatment of Mild to Moderate COVID-19 in Non-Hospitalized Setting Recruiting Phase 2 Nov/20/2020 Jan/31/2022
NCT04518410 ACTIV-2: A Study for Outpatients With COVID-19 Recruiting Phase 2|Phase 3 Aug/19/2020 Dec/31/2023
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
NCT04411628 A Study of LY3819253 (LY-CoV555) in Participants Hospitalized for COVID-19 Completed Phase 1 May/28/2020 Aug/26/2020
NCT04603651 Expanded Access Program to Provide Bamlanivimab (LY3819253) for the Treatment of COVID-19 No longer available Jan/01/1970 Jan/01/1970