Tixagevimab/cilgavimab

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Tixagevimab/cilgavimab
Tixagevimab-cilgavimab binding SARS-CoV-2 spike protein 7L7E.png
Tixagevimab (teal, right) and cilgavimab (purple, left) binding the spike protein RBD. From PDB: 7L7E​.
Combination of
TixagevimabMonoclonal antibody
CilgavimabMonoclonal antibody
Clinical data
Trade namesEvusheld
Other namesAZD7442
AHFS/Drugs.comMonograph
MedlinePlusa621058
License data
Routes of
administration		Intramuscular
ATC code
Legal status
Legal status
Identifiers
KEGG
Tixagevimab
Clinical data
Drug classAntiviral
ATC code
  • None
Identifiers
CAS Number
DrugBank
UNII
KEGG
Chemical and physical data
FormulaC6488H10034N1746O2038S50
Molar mass146706.82 g·mol−1
Cilgavimab
Clinical data
Drug classAntiviral
ATC code
  • None
Identifiers
CAS Number
DrugBank
UNII
KEGG
Chemical and physical data
FormulaC6626H10218N1750O2078S44
Molar mass149053.44 g·mol−1

Tixagevimab/cilgavimab, sold under the brand name Evusheld is a combination of two human monoclonal antibodies, tixagevimab (AZD8895) and cilgavimab (AZD1061) targeted against the surface spike protein of SARS-CoV-2[5][6] used to prevent COVID-19.[7] It is being developed by British-Swedish multinational pharmaceutical and biotechnology company AstraZeneca.[8][9] It is co-packaged and given as two separate consecutive intramuscular injections (one injection per monoclonal antibody, given in immediate succession).[2]

Development[]

In 2020, researchers at Vanderbilt University Medical Center discovered particularly potent monoclonal antibodies, isolated from COVID-19 patients infected with a SARS-CoV-2 circulating at that time. Initially designated COV2-2196 and COV2-2130, antibody engineering was used to transfer their SARS-CoV-2 binding specificity to IgG scaffolds that would last longer in the body, and these engineered antibodies were named AZD8895 and AZD1061, respectively (and the combination was called AZD7442).[10]

To evaluate the antibodies' potential as monoclonal antibody based prophylaxis (prevention), the 'Provent' clinical trial enrolled 5,000 high risk but not yet infected individuals and monitored them for 15 months.[11][12] The trial reported that those receiving the cocktail showed a 77% reduction in symptomatic COVID-19 and that there were no severe cases or deaths. AstraZeneca also found that the antibody cocktail "neutralizes recent emergent SARS-CoV-2 viral variants, including the Delta variant".[9]

In contrast to pre-exposure prophylaxis, the Storm Chaser study of already-exposed people (post-exposure prophylaxis) did not meet its primary endpoint, which was prevention of symptomatic COVID-19 in people already exposed. AZD7442 was administered to 1,000 volunteers who had recently been exposed to COVID.[11]

Society and culture[]

Legal status[]

In October 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) started a rolling review of tixagevimab/cilgavimab, which is being developed by AstraZeneca AB, for the prevention of COVID-19 in adults.[13]

Also in October 2021, AstraZeneca requested Emergency Use Authorization for tixagevimab/cilgavimab to prevent COVID-19 from the U.S. Food and Drug Administration (FDA).[14][15]

On 14 November 2021, Bahrain authorized it for emergency use.[16]

On 8 December 2021, the U.S. Food and Drug Administration (FDA) granted emergency use authorization of this combination to prevent COVID-19 (before exposure) in people with weakened immunity or who cannot be fully vaccinated due to a history of severe reaction to coronavirus vaccines.[17] and in certain people aged 12 years of age and older weighing at least 40 kilograms (88 lb).[2] The product is only authorized for those individuals who are not infected with the SARS-CoV-2 virus and who have not recently been exposed to an individual infected with SARS-CoV-2.[2]

References[]

  1. ^ "Evusheld- azd7442 kit". DailyMed. AstraZeneca. 20 December 2021. Archived from the original on 5 January 2022. Retrieved 20 January 2022.
  2. ^ a b c d "Coronavirus (COVID-19) Update: FDA Authorizes New Long-Acting Monoclonal Antibodies for Pre-exposure Prevention of COVID-19 in Certain Individuals". U.S. Food and Drug Administration (FDA) (Press release). 8 December 2021. Retrieved 9 December 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  3. ^ O'Shaughnessy A (20 December 2021). "Re: Emergency Use Authorization 104" (PDF). Food and Drug Administration. Letter to AstraZeneca Pharmaceuticals LP | Attention: Stacey Cromer Berman, PhD. Archived from the original on 29 December 2021. Retrieved 18 January 2022.
  4. ^ "FDA authorizes revisions to Evusheld dosing". U.S. Food and Drug Administration (FDA). 24 February 2022. Retrieved 27 February 2022.
  5. ^ "Cilgavimab". IUPHAR/BPS Guide to PHARMACOLOGY. IUPHAR. 27 December 2021. Retrieved 27 December 2021.
  6. ^ "Tixagevimab". IUPHAR/BPS Guide to PHARMACOLOGY. IUPHAR. 27 December 2021. Retrieved 27 December 2021.
  7. ^ Abramowicz M, Zuccotti G, Pflomm JM, eds. (January 2022). "Tixagevimab and Cilgavimab (Evusheld) for Pre-Exposure Prophylaxis of COVID-19". JAMA. 327 (4): 384–385. doi:10.1001/jama.2021.24931. PMID 35076671.
  8. ^ Ray S (21 August 2021). "AstraZeneca's Covid-19 Antibody Therapy Effective In Preventing Symptoms Among High-Risk Groups, Trial Finds". Forbes. ISSN 0015-6914. Archived from the original on 21 August 2021. Retrieved 18 January 2022.
  9. ^ a b Goriainoff AO (20 August 2021). "AstraZeneca Says AZD7442 Antibody Phase 3 Trial Met Primary Endpoint in Preventing Covid-19". MarketWatch. Archived from the original on 21 August 2021. Retrieved 18 January 2022.
  10. ^ Dong J, Zost SJ, Greaney AJ, Starr TN, Dingens AS, Chen EC, et al. (October 2021). "Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail". Nature Microbiology. 6 (10): 1233–1244. doi:10.1038/s41564-021-00972-2. LCCN 2016247755. OCLC 959654134. PMC 8543371. PMID 34548634.
  11. ^ a b Haridy R (23 August 2021). ""Game-changing" antibody cocktail prevents COVID-19 in the chronically ill". New Atlas. Retrieved 23 August 2021.
  12. ^ "AZD7442 PROVENT Phase III prophylaxis trial met primary endpoint in preventing COVID-19". AstraZeneca (Press release). 20 August 2021. Retrieved 15 October 2021.
  13. ^ "EMA starts rolling review of Evusheld (tixagevimab and cilgavimab)". European Medicines Agency. 14 October 2021. Retrieved 15 October 2021.
  14. ^ "AZD7442 request for Emergency Use Authorization for COVID-19 prophylaxis filed in US". AstraZeneca US (Press release). 5 October 2021. Retrieved 15 October 2021.
  15. ^ "AZD7442 request for Emergency Use Authorization for COVID-19 prophylaxis filed in US". AstraZeneca (Press release). 5 October 2021. Retrieved 15 October 2021.
  16. ^ Abd-Alaziz M, Elhamy A (14 November 2021). Macfie N (ed.). "Bahrain authorizes AstraZeneca's anti-COVID drug for emergency use". Reuters. Archived from the original on 23 November 2021. Retrieved 18 January 2022.
  17. ^ Mishra M, Satija B (8 December 2021). Dasgupta S (ed.). "U.S. FDA authorizes use of AstraZeneca COVID-19 antibody cocktail". Reuters. Archived from the original on 13 January 2022. Retrieved 18 January 2022.

External links[]

  • "Tixagevimab". Drug Information Portal. U.S. National Library of Medicine.
  • "Cilgavimab". Drug Information Portal. U.S. National Library of Medicine.
  • Clinical trial number NCT04625972 for "Phase III Double-blind, Placebo-controlled Study of AZD7442 for Post-exposure Prophylaxis of COVID-19 in Adults (STORM CHASER)" at ClinicalTrials.gov
  • Clinical trial number NCT04625725 for "Phase III Double-blind, Placebo-controlled Study of AZD7442 for Pre-exposure Prophylaxis of COVID-19 in Adult. (PROVENT)" at ClinicalTrials.gov
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