Tixagevimab/cilgavimab

Tixagevimab/cilgavimab
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]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
    Routes of
    use    		Intramuscular
    Typical dose150mg/150mg[1]
    External links
    AHFS/Drugs.comMonograph
    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 also used to prevent mild to moderate COVID-19 disease.[17] 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.[18][19]

    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).[20]

    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.[21][22] 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,[19] and the Omicron variant.[23]

    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.[21]

    Society and culture

    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.[24] 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).[25][26]

    In November 2021, Bahrain authorized it for emergency use.[27]

    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.[28] 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.[29][30][31]

    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).[32] The applicant for this medicinal product is AstraZeneca AB.[32] It has since been granted approval for use in the UK[33][34] and in the European Union.[35]

    References

    1. 1 2 3 4 5 6 7 8 9 10 11 12 "Evusheld". Archived from the original on 16 April 2022. Retrieved 26 April 2022. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    2. 1 2 3 4 5 6 7 8 9 "Tixagevimab and Cilgavimab Monograph for Professionals". Drugs.com. Archived from the original on 21 April 2022. Retrieved 26 April 2022. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    3. 1 2 "Evusheld". Therapeutic Goods Administration (TGA). 7 March 2022. Archived from the original on 24 March 2022. Retrieved 23 March 2022. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    4. ↑ "Evusheld". Therapeutic Goods Administration (TGA). Archived from the original on 24 March 2022. Retrieved 23 March 2022. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    5. ↑ "AusPAR: Tixagevimab and cilgavimab". Therapeutic Goods Administration (TGA). 11 March 2022. Archived from the original on 24 March 2022. Retrieved 23 March 2022. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    6. ↑ "Evusheld- azd7442 kit". DailyMed. AstraZeneca. 20 December 2021. Archived from the original on 5 January 2022. Retrieved 20 January 2022. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    7. 1 2 3 4 "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. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    10. 1 2 "Evusheld EPAR". European Medicines Agency (EMA). 22 March 2022. Archived from the original on 16 April 2022. Retrieved 24 April 2022. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    11. ↑ "Evusheld". Union Register of medicinal products. 25 March 2022. Archived from the original on 28 March 2022. Retrieved 24 April 2022. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    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. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    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. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    14. ↑ "Evusheld Prices and Evusheld Coupons". GoodRx. Archived from the original on 28 April 2022. Retrieved 26 April 2022. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    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. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    17. ↑ Government of Canada, Health Canada (25 August 2010). "Notice of Compliance (NOC) online query". health-products.canada.ca. Archived from the original on 19 October 2022. Retrieved 20 October 2022. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    18. ↑ 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. {{cite news}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    19. 1 2 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. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    20. ↑ 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.
    21. 1 2 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. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    22. ↑ "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.
    23. ↑ 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. {{cite news}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    24. ↑ "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. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    25. ↑ "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.
    26. ↑ "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.
    27. ↑ 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. {{cite news}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    28. ↑ 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. {{cite news}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    29. ↑ 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. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    30. ↑ 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. {{cite news}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    31. ↑ "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. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    32. 1 2 "Evusheld: Pending EC decision". European Medicines Agency (EMA). 25 March 2022. Archived from the original on 25 March 2022. Retrieved 25 March 2022. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help) Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
    33. ↑ "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. {{cite news}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    34. ↑ 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. {{cite news}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    35. ↑ "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. {{cite news}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    Identifiers:
    • "Tixagevimab". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 15 October 2021. Retrieved 24 April 2022. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    • "Cilgavimab". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 15 October 2021. Retrieved 24 April 2022. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
    • 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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