Tixagevimab

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

Phase of research

Emergency use authorization

How it helps

Antiviral

Drug status

Experimental

10
Supporting references
0
Contradictory references
4
AI-suggested references
1
Clinical trials

General information

Tixagevimab is a recombinant monoclonal antibody (IgG1κ), which was derived from COV-2196. It was developed by Vanderbilt Vaccine Center in collaboration with AstraZeneca. It binds SARS-CoV-2 Spike RBD (Dong et al., 2021; Zost et al., 2020a; Zost et al., 2020b).

Tixagevimab is co-packaged, under the trademark Evusheld™, and co-administered (as separate infusions) with cilgavimab. Evusheld™ by AstraZeneca Pharmaceuticals LP has been granted an emergency use authorization by the FDA (USA) for use in immunocompromised individuals aged 12+ years (weight 40+ kg) as a pre-exposure prophylaxis when vaccination is either not possible or effective. It is under rolling review by EMA (EU).

In vitro data indicate that the antibody (cocktail) is either inefficient (Cao et al., 2021) or less efficient against the Omicron strain of SARS-CoV-2 compared to previous variants of concern (Takashita et al., 2022).

 

Tixagevimab on DrugBank
Tixagevimab on Wikipedia


Synonyms

AZD8895; AZD-8895; AZD7442 (combined with Cilgavimab); AZD-7442 (combined with Cilgavimab)


Marketed as

EVUSHELD (co-packaged with Cilgavimab)

 


Supporting references

Link Tested on Impact factor Notes Publication date
Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail
Spike protein Spike variant Crystallization Protein factor In vitro Mechanism Antibody
in vitro; Vero E6 cells; Vero-hACE2-TMPRSS2 cells; SARS-CoV-2 (various strains) 17.75

Based on crystallization data, the antibody binds SARS-CoV-2 Spike RBD with the paratope being germ-line encoded and at the interface of light and heavy chain. The antibody neutralized various strains of SARS-CoV-2 in vitro (D614G, D614G + N501Y, alpha, beta, gamma, epsilon, kappa, and delta). As its activity is mostly synergic with cilgavimab and the profile of escape mutations is different, the authors argue for the use of a cocktail of these two antibodies (Evusheld™). 

Sep/21/2021
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

Tixagevimab retained only weak anti-omicron (SARS-CoV-2) activity in vitro. It neutralized the omicron variant in combination with cilgavimab; however, the efficacy of such formulation was significantly lower compared to the efficacy against the other strains tested. 

Jan/26/2022
The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in non-human primates and has an extended half-life in humans
Spike protein ACE2 Spike variant Protein factor Animal model In vitro Phase I clinical trial Randomized controlled double-blind trial Antibody
HEK293T-ACE2 cells; Vero E6 cells; rhesus macaques; cynomolgus macaques; healthy humans aged 18–55 years 17.96

Tixagevimab blocked binding of SARS-CoV-2 Spike to ACE2 a virus cell entry in vitro. It also neutralized tested variants (WT, Alpha, Beta, Gamma, and Delta). In an animal model, the antibody in combination with cilgavimab prevented SARS-CoV-2 infection if administered prophylactically and accelerated viral clearance from lungs if administered therapeutically. Administration of the mixed formulation to healthy individuals provided high and long half-life serum neutralizing titres. Sample size: 50 (in 5 sub-cohorts) + 10 placebo. Dosage: 150 mg IM, 150 mg IV, 500 mg IV or 1,500 mg IV sequentially with cilgavimab or 1,500 mg mixed with cilgavimab. Main outcome: Safety and tolerability.

Jan/25/2022
SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses
Spike protein ACE2 RNA DNA Spike variant Crystallization Biophysical assay Protein factor In vitro Antibody Mixed substance
sera from vaccinated or convalescent individuals; VeroE6/TMPRSS2 cells; SARS-CoV-2 (various strains) 41.58

Tixagevimab combined with Cilgavimab neutralized the Omicron variant in vitro (albeit with several-fold lower potency compared to previous variants of concern). 

Jan/04/2022
Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera
Spike protein Spike variant Crystallization Protein factor In vitro Mechanism Antibody
in vitro biophysical assay; crystallization; sera of COVID-19 convalescent patients or vaccinated adults; Vero cells; SARS-CoV-2 (SARS-CoV-2/human/AUS/VIC01/2020 and SAR-CoV-2/B.1.1.7) 41.58

The antibody displayed only a slight reduction in B.1.1.7 variant neutralization. 

Feb/18/2021
Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera
Spike protein RNA DNA Spike variant Biophysical assay Protein factor In vitro Antibody Mixed substance
in vitro biophysical assay; plasma of COVID-19 (Beta strain) convalescent patients or vaccinated adults; Vero cells; SARS-CoV-2 (SARS-CoV-2/human/AUS/VIC01/2020 and SARS-CoV-2/B.1.351) 41.58

Binds SARS-CoV-2 RBD and neutralizes the virus in vitro in the case of the Beta variant (slightly weaker compared to the original strain, however). 

Feb/23/2021
Antibody evasion by the P.1 strain of SARS-CoV-2
Spike protein RNA DNA Spike variant Crystallization Biophysical assay Protein factor In vitro Antibody Mixed substance
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

A modest reduction in neutralization potency against Beta and Gamma strains of SARS-CoV-2 was observed. The antibody retained some of its activity, however. 

Mar/30/2021
Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum
Spike protein RNA DNA Spike variant Crystallization Biophysical assay Protein factor In vitro Antibody Mixed substance
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

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

Jun/17/2021
Resistance of SARS-CoV-2 Omicron BA.1 and BA.2 Variants to Vaccine-Elicited Sera and Therapeutic Monoclonal Antibodies
Spike protein Spike variant Protein factor In vitro Antibody In silico
in silico; HEK293T cells; (lentiviral) SARS-CoV-2 pseudotypes (D614G, Delta, BA.1, and BA.2) 5.82

The Omicron variants BA.1 and BA.2 displayed significant decrease in neutralization by the antibody in vitro. The combination of Tixagevimab with Cilgavimab (a formulation “Evusheld”), retained more neutralizing activity. 

Jun/18/2022
Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies
Spike protein Spike variant Protein factor In vitro Antibody Cohort study
Immunocompromised individuals; Vero E6 cells; S-Fuse cells

The combination of tixagevimab with cilgavimab ("Evusheld" formulation) retained greater neutralizing activity against Delta and Omicron variant. Sample size: 29. 

Mar/23/2022

AI-suggested references

Clinical trials

ID Title Status Phase Start date Completion date
NCT05234398 TIXAGEVIMAB/CILGAVIMAB Protection of Covid-19 in Transplanted Patients Not yet recruiting Feb/01/2022 Aug/01/2023
  • Alternative id - 69HCL21_1433|2021-A03245-36
  • Interventions - Biological: Blood and saliva samplings
  • Study type - Observational
  • Study results - No Results Available
  • Locations - Service de Néphrologie, Transplantation et Immunologie Clinique Hôpital Edouard Herriot - Hospices Civils de Lyon, Lyon, France|Service de Néphrologie et Transplantation, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
  • Study designs - Observational Model: Other|Time Perspective: Prospective
  • Enrollment - 160
  • Age - 18 Years and older   (Adult, Older Adult)
  • Outcome measures - Percentage of patients whose serum has viral neutralization capacity in vitro at M6 after TIXAGEVIMAB/CILGAVIMAB injection.