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
Names
Trade namesEvusheld
Other namesAZD7442
Clinical data
Main usesPrevent COVID-19 before exposure[1][2]
Side effectsAllergic reaction, injection site pain[1]
Pregnancy
category
Routes of
use
Intramuscular
Typical dose150mg/150mg[1]
External links
AHFS/Drugs.comMonograph
US NLMTixagevimab/cilgavimab
MedlinePlusa621058
Legal
License data
Legal status

Tixagevimab/cilgavimab, sold under the brand name Evusheld, is a medication used to prevent COVID-19 before exposure.[1][2] It may be used in those who weight more than 40 kg or are older than 12 years.[1] It is given by injection into a muscle.[1] Evidence supports benefits for up to six month.[1]

Common side effects are allergic reactions, headaches, tiredness, and pain at the site of injection.[1][2] Other serious side effects may include anaphylaxis and heart problems.[2] Safety in pregnancy is unclear.[2] It is a combination of two monoclonal antibody, tixagevimab and cilgavimab.[1] It works by binding the spike protein of SARS-CoV-2 which prevents it from entering cells.[1]

The combination was approved for medical use in Europe in March and in Canada in April of 2022.[1][12] In the United States it received Emergency Use Authorization in December of 2021.[2] In the United States the government pays about 855 USD per dose.[13] The cost to the individual is generally less than 10 USD.[14]

Medical uses

Tixagevimab/cilgavimab is a medication used to prevent COVID-19 before exposure, in those with poor immune function.[15][2] It decreases the risk of infection by about 77%.[16]

It is not used after exposure to SARS-CoV-2 or in those who already have symptoms of COVID-19.[2] Its use should not prevent vaccination against COVID-19.[2]

Dosage

It is co-packaged and given as two separate intramuscular injections (one injection per monoclonal antibody, given in immediate succession).[7] It is given as 150 mg of tixagevimab and 150 mg of cilgavimab.[1] Evidence for repeated doses is unclear.[2]

History

It was developed by AstraZeneca.[17][18]

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).[19]

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.[20][21] 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,[18] and the Omicron variant.[22]

In contrast to use before exposure, the Storm Chaser study of of use after exposure exposure but before symptoms did not meet its primary endpoint, which was prevention of symptomatic COVID-19.[20]

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.[23] It was approved for medical use in the European Union in March 2022.[10]

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).[24][25]

In November 2021, Bahrain authorized it for emergency use.[26]

In 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.[27] and in certain people aged 12 years of age and older weighing at least 40 kilograms (88 lb).[7] 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.[7]

Although Evusheld is FDA-approved for emergency use in the U.S, it is estimated that around 80% of the available doses sit unused in warehouses and on pharmacy and hospital shelves due to confusion among patients and health care providers.[28][29][30]

In March 2022, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Evusheld, intended for the pre-exposure prophylaxis of COVID-19 in adults and adolescents aged 12 years and older weighing at least 40 kilograms (88 lb).[31] The applicant for this medicinal product is AstraZeneca AB.[31] It has since been granted approval for use in the UK[32][33] and in the European Union.[34]

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 "Evusheld". Archived from the original on 16 April 2022. Retrieved 26 April 2022.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 "Tixagevimab and Cilgavimab Monograph for Professionals". Drugs.com. Archived from the original on 21 April 2022. Retrieved 26 April 2022.
  3. 3.0 3.1 "Evusheld". Therapeutic Goods Administration (TGA). 7 March 2022. Archived from the original on 24 March 2022. Retrieved 23 March 2022.
  4. "Evusheld". Therapeutic Goods Administration (TGA). Archived from the original on 24 March 2022. Retrieved 23 March 2022.
  5. "AusPAR: Tixagevimab and cilgavimab". Therapeutic Goods Administration (TGA). 11 March 2022. Archived from the original on 24 March 2022. Retrieved 23 March 2022.
  6. "Evusheld- azd7442 kit". DailyMed. AstraZeneca. 20 December 2021. Archived from the original on 5 January 2022. Retrieved 20 January 2022.
  7. 7.0 7.1 7.2 7.3 "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. Archived from the original on 28 April 2022. Retrieved 9 December 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  8. 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.
  9. "FDA authorizes revisions to Evusheld dosing". U.S. Food and Drug Administration (FDA). 24 February 2022. Archived from the original on 27 February 2022. Retrieved 27 February 2022.
  10. 10.0 10.1 "Evusheld EPAR". European Medicines Agency (EMA). 22 March 2022. Archived from the original on 16 April 2022. Retrieved 24 April 2022.
  11. "Evusheld". Union Register of medicinal products. 25 March 2022. Archived from the original on 28 March 2022. Retrieved 24 April 2022.
  12. Canada, Health (14 April 2022). "Health Canada authorizes Evusheld for the prevention of COVID-19 in immune compromised adults and children". www.canada.ca. Archived from the original on 25 April 2022. Retrieved 26 April 2022.
  13. McDade, Aaron (11 February 2022). "Army awards AstraZeneca $855M contract for Evusheld COVID treatment". Newsweek. Archived from the original on 26 April 2022. Retrieved 26 April 2022.
  14. "Evusheld Prices and Evusheld Coupons". GoodRx. Archived from the original on 28 April 2022. Retrieved 26 April 2022.
  15. 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.
  16. "FDA Authorizes Evusheld: First COVID-19 PrEP Drug". GoodRx. Archived from the original on 16 April 2022. Retrieved 26 April 2022.
  17. 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.
  18. 18.0 18.1 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.
  19. 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.
  20. 20.0 20.1 Haridy R (23 August 2021). ""Game-changing" antibody cocktail prevents COVID-19 in the chronically ill". New Atlas. Archived from the original on 10 October 2021. Retrieved 23 August 2021.
  21. "AZD7442 PROVENT Phase III prophylaxis trial met primary endpoint in preventing COVID-19". AstraZeneca (Press release). 20 August 2021. Archived from the original on 13 October 2021. Retrieved 15 October 2021.
  22. Reuters (21 March 2022). "AstraZeneca COVID drug neutralises Omicron sub-variants in lab study". Reuters. Archived from the original on 22 April 2022. Retrieved 5 April 2022.
  23. "EMA starts rolling review of Evusheld (tixagevimab and cilgavimab)". European Medicines Agency (EMA). 14 October 2021. Archived from the original on 8 November 2021. Retrieved 15 October 2021.
  24. "AZD7442 request for Emergency Use Authorization for COVID-19 prophylaxis filed in US". AstraZeneca US (Press release). 5 October 2021. Archived from the original on 15 October 2021. Retrieved 15 October 2021.
  25. "AZD7442 request for Emergency Use Authorization for COVID-19 prophylaxis filed in US". AstraZeneca (Press release). 5 October 2021. Archived from the original on 27 October 2021. Retrieved 15 October 2021.
  26. 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.
  27. 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.
  28. CNN, Elizabeth Cohen and Danielle Herman (24 March 2022). "Vulnerable Americans are desperate to find this Covid-19 drug. Thousands of boxes are sitting around unused". CNN. Archived from the original on 15 April 2022. Retrieved 5 April 2022.
  29. Morris, Amanda; Stolberg, Sheryl Gay (6 March 2022). "High Demand for Drug to Prevent Covid in the Vulnerable, Yet Doses Go Unused". The New York Times. ISSN 0362-4331. Archived from the original on 24 April 2022. Retrieved 5 April 2022.
  30. "It was already hard to find Evusheld COVID prevention therapy. Now it's harder". The Seattle Times. 21 March 2022. Archived from the original on 18 April 2022. Retrieved 5 April 2022.
  31. 31.0 31.1 "Evusheld: Pending EC decision". European Medicines Agency (EMA). 25 March 2022. Archived from the original on 25 March 2022. Retrieved 25 March 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  32. "AstraZeneca's Evusheld Covid-prevention drug gets UK approval". The Guardian. 17 March 2022. Archived from the original on 25 April 2022. Retrieved 5 April 2022.
  33. Fourcade, Marthe. "Astra Covid Antibody Gets U.K. Approval for People With Poor Immunity". Bloomberg. Archived from the original on 6 April 2022. Retrieved 5 April 2022.
  34. "New drug that prevents you from catching COVID-19 given green light in Europe". Fortune. Archived from the original on 25 April 2022. Retrieved 5 April 2022.

External links

Identifiers:
  • "Tixagevimab". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 15 October 2021. Retrieved 24 April 2022.
  • "Cilgavimab". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 15 October 2021. Retrieved 24 April 2022.
  • 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