Evusheld has emergency use authorisation
for pre-exposure prophylaxis (prevention) of COVID-19
AstraZeneca today welcomes the announcement from the US government for the purchase of an additional 500,000 doses of Evusheld (tixagevimab co-packaged with cilgavimab), a long-acting antibody (LAAB) combination for the pre-exposure prophylaxis (prevention) of COVID-19. Delivery of the additional 500,000 doses is anticipated in the first quarter of 2022.
This follows the previous government agreement for the purchase of 700,000 doses of Evusheld.
Iskra Reic, Executive Vice President, Vaccines and Immune Therapies, AstraZeneca, said: “Today’s agreement will bring protection to some of the most vulnerable people in the US, including the immunocompromised, who may receive limited or no protection from vaccines and currently have few options in the face of the rapid rise in COVID-19 cases seen in recent weeks. Evusheld isthe only antibody therapy to receive emergency use authorisation in the US for pre-exposure prophylaxis and one of only two authorised antibody therapies to show neutralising activity against Omicron and all other variants.”
Additional details on the agreement will be forthcoming in coming weeks.
Evusheld, formerly known as AZD7442, is a combination of two LAABs – tixagevimab (AZD8895) and cilgavimab (AZD1061) – derived from B-cells donated by convalescent patients after SARS-CoV-2 virus.
In December 2021, the FDA issued an EUA for the use of Evusheld for the pre-exposure prophylaxis (prevention) of COVID-19 in adults and adolescents (aged 12 and older who weigh 40kg or more) with moderate to severe immune compromise due to a medical condition or immunosuppressive medications and who may not mount an adequate immune response to COVID-19 vaccination, as well as those individuals for whom COVID-19 vaccination is not recommended due to a history of severe adverse reaction to a COVID-19 vaccine. Evusheld is the only antibody therapy authorised in the US to prevent COVID-19 symptoms before virus exposure. Evusheld is also authorised for emergency use for prevention of COVID-19 in several other countries.
About 2% of the global population is considered at increased risk of an inadequate response to a COVID-19 vaccine and may benefit from Evusheld for pre-exposure prophylaxis of COVID-19.1-2 Recent emerging evidence indicate that protecting these vulnerable populations from getting COVID-19 could help prevent viral evolution that is an important factor in the emergence of variants.3
Recent live and pseudovirus studies from the US Food and Drug Administration, University College Oxford, UK and Washington University School of Medicine, St. Louis, US showed that Evusheld retains neutralising activity against the Omicron variant (B.1.1.529) and all tested SARS-CoV-2 variants of concern to date.4-7 By combining two particularly potent antibodies with different and complementary activities against the virus, Evusheld was designed to evade potential resistance with the emergence of new SARS-CoV-2 variants.
Evusheld is being developed with support from the US government, including federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority in partnership with the Department of Defense; Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, under Contract No. W911QY-21-9-0001.
Discovered by Vanderbilt University Medical Center and licensed to AstraZeneca in June 2020, the human monoclonal antibodies bind to distinct sites on the SARS-CoV-2 spike protein8 and were optimized by AstraZeneca with half-life extension and reduced Fc receptor and complement C1q binding. The half-life extension more than triples the durability of its action compared to conventional antibodies and could afford up to 12 months of protection from COVID-19 following a single administration;9-11 data from the Phase III PROVENT trial show protection lasting at least six months.12 The reduced Fc receptor binding aims to minimize the risk of antibody-dependent enhancement of disease – a phenomenon in which virus-specific antibodies promote, rather than inhibit, infection and/or disease.13 Evusheld is delivered as an intramuscular dose of 150mg tixagevimab and 150mg cilgavimab administered in two separate, consecutive injections.
Under the terms of the licensing agreement with Vanderbilt, AstraZeneca will pay single-digit royalties on future net sales.
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
1. Harpaz R, et al. Prevalence of immunosuppression among US adults, 2013. JAMA. 2016 Dec 20;316(23):2547-2548. Available at: https://doi.org/10.1001/jama.2016.16477
2. AstraZeneca data on file.
3. Corey L, et al. SARS-CoV-2 Variants in Patients with Immunosuppression. N Engl J Med 2021; 385:562-566. DOI: 10.1056/NEJMsb2104756.
4. Dejnirattisai W, et al. Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses. bioRxiv. 2021; doi: 10.1101/2021.12.03.471045.
5. VanBlargan LA, et al. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by several therapeutic monoclonal antibodies. bioRxiv. 2021; doi: 10.1101/2021.12.15.472828.
6. National Institutes of Health. National Center for Advancing Translational Sciences Open Data Portal. SARS-CoV-2 Variants & Therapeutics. AZD7442 (AZD8895 and AZD1061; mAbs for SARS-CoV-2) Omicron Antiviral Resistance Information. Available at: https://opendata.ncats.nih.gov/variant/datasets?id=160 [Last accessed January 2022].
7. National Institutes of Health. National Center for Advancing Translational Sciences Open Data Portal. SARS-CoV-2 Variants & Therapeutics, All Variants Reported in vitro Therapeutic Activity. Available at: https://opendata.ncats.nih.gov/variant/activity. [Last accessed: January 2022].
8. Dong J, et al. Genetic and structural basis for recognition of SARS-CoV-2 spike protein by a two-antibody cocktail. bioRxiv. 2021; doi: 10.1101/2021.01.27.428529.
9. Robbie GJ, et al. A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults. Antimicrob Agents Chemother. 2013; 57 (12): 6147-53.
10. Griffin MP, et al. Safety, tolerability, and pharmacokinetics of MEDI8897, the respiratory syncytial virus prefusion F-targeting monoclonal antibody with an extended half-life, in healthy adults. Antimicrob Agents Chemother. 2017; 61(3): e01714-16.
11. Domachowske JB, et al. Safety, tolerability and pharmacokinetics of MEDI8897, an extended half-life single-dose respiratory syncytial virus prefusion F-targeting monoclonal antibody administered as a single dose to healthy preterm infants. Pediatr Infect Dis J. 2018; 37(9): 886-892.
12. AstraZeneca news release. New analyses of two AZD7442 COVID-19 trials in high-risk populations confirm robust efficacy and long-term prevention. Available at: https://www.astrazeneca.com/media-centre/press-releases/2021/new-analyses-of-two-azd7442-covid-19-phase-iii-trials-in-high-risk-populations-confirm-robust-efficacy-and-long-term-prevention.html. [Last accessed: January 2022].
13. van Erp EA, et al. Fc-mediated antibody effector functions during respiratory syncytial virus infection and disease. Front Immunol. 2019; 10: 548.