Tixagevimab/cilgavimab

Tixagevimab/cilgavimab is a combination of two human monoclonal antibodies, tixagevimab (AZD8895) and cilgavimab (AZD1061) used to prevent COVID-19. It is being developed by British-Swedish multinational pharmaceutical and biotechnology company AstraZeneca.[3][4] It is co-packaged and given as two separate consecutive intramuscular injections (one injection per monoclonal antibody, given in immediate succession).[1]

Tixagevimab/cilgavimab
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
Routes of
administration		Intramuscular
ATC code
  • None
Legal status
Legal status

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).[5]

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.[6][7] 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".[4]

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.[6]

Regulatory review

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.[8]

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).[9][10]

Emergency use authorization

On 14 November 2021, Bahrain granted emergency use authorization.[11]

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.[12] The FDA issued an emergency use authorization (EUA) for AstraZeneca's Evusheld (tixagevimab co-packaged with cilgavimab and administered together) for the pre-exposure prophylaxis (prevention) of COVID-19 in certain people aged 12 years of age and older weighing at least 40 kilograms (88 lb).[1] The product is only authorized for those individuals who are not currently infected with the SARS-CoV-2 virus and who have not recently been exposed to an individual infected with SARS-CoV-2.[1]

References
  1. "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. This article incorporates text from this source, which is in the public domain.
  2. https://www.fda.gov/media/154704/download
  3. Ray S (21 August 2021). "AstraZeneca's Covid-19 Antibody Therapy Effective In Preventing Symptoms Among High-Risk Groups, Trial Finds". Forbes. Archived from the original on 21 August 2021. Retrieved 21 August 2021.
  4. 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 21 August 2021.
  5. 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. PMC 8543371. PMID 34548634.
  6. Haridy, Rich (23 August 2021). ""Game-changing" antibody cocktail prevents COVID-19 in the chronically ill". New Atlas. Retrieved 23 August 2021.
  7. "AZD7442 PROVENT Phase III prophylaxis trial met primary endpoint in preventing COVID-19". AstraZeneca (Press release). 20 August 2021. Retrieved 15 October 2021.
  8. "EMA starts rolling review of Evusheld (tixagevimab and cilgavimab)". European Medicines Agency. 14 October 2021. Retrieved 15 October 2021.
  9. "AZD7442 request for Emergency Use Authorization for COVID-19 prophylaxis filed in US". AstraZeneca US (Press release). 5 October 2021. Retrieved 15 October 2021.
  10. "AZD7442 request for Emergency Use Authorization for COVID-19 prophylaxis filed in US". AstraZeneca (Press release). 5 October 2021. Retrieved 15 October 2021.
  11. "Bahrain authorizes AstraZeneca's anti-COVID drug for emergency use". Reuters. 14 November 2021. Retrieved 14 November 2021.
  12. Reuters (8 December 2021). "U.S. FDA authorizes use of AstraZeneca COVID-19 antibody cocktail". Reuters. Retrieved 9 December 2021.
  • "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
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.