First in vivo data from Washington University show Evusheld reduces viral burden of all tested Omicron subvariants in the lungs
New preclinical authentic ‘live’ virus data from Washington University School of Medicine demonstrated that Evusheld (tixagevimab co-packaged with cilgavimab) retains potent neutralising activity against the emerging and highly transmissible Omicron SARS-CoV-2 BA.2 subvariant.1 The data also showed that Evusheld retains activity against Omicron BA.1 and BA.1.1.1
In addition, in vivo (live organism) data generated using mice infected with Omicron BA.1, BA.1.1 and BA.2 demonstrated that Evusheld significantly reduced the viral burden and limited inflammation in the lungs for all three subvariants.1 SARS-CoV-2 viral load is associated with increased disease severity and mortality as well as post-COVID conditions (long COVID).2,3
The study used a transgenic mouse model to evaluate Evusheld in pre-exposure prophylaxis (prevention) of COVID-19, similar to how Evusheld is used in the clinic. These are the first in vivo data evaluating Evusheld’s efficacy against the Omicron variants versus previous in vitro neutralising activity assays in cultured cells.
The Washington University findings were reported online on bioRxiv, a preprint server.
Michael S. Diamond, MD, PhD, The Herbert S. Gasser Professor, Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University, US, said: “These new in vivo mouse model data confirm previous in vitro neutralisation activity results for Evusheld against Omicron. The findings demonstrate that Evusheld was effective at protecting against infection in the lungs, a critical disease site for severe COVID-19, across all Omicron subvariants tested.”
John Perez, Senior Vice President, Head of Late Development, Vaccines & Immune Therapies, AstraZeneca, said: “These important data show that Evusheld reduced viral burden and limited inflammation caused by Omicron. The findings further support Evusheld as a potential important option to help protect vulnerable patients such as the immunocompromised who could face poor outcomes if they were to become infected with COVID-19.”
Additional ‘live’ virus data from Aix-Marseilles University and pseudovirus data from the US Food and Drug Administration also demonstrated that Evusheld neutralises BA.2.4,5 According to the World Health Organization, cases of BA.2 have been identified in 85 countries to date, with prevalence increasing in several parts of the world.6
Evusheld is authorised for pre-exposure prophylaxis (prevention) of COVID-19 in the US and several other countries. Evusheld is intended for vulnerable populations who have a medical condition or are receiving immunosuppressive medications or treatments and may not mount an adequate immune response to COVID-19 vaccination, as well as those individuals for whom COVID-19 vaccination is not recommended.
Notes
Evusheld
Evusheld, formerly known as AZD7442, is a combination of two long-acting antibodies – tixagevimab (AZD8895) and cilgavimab (AZD1061) – derived from B-cells donated by convalescent patients after SARS-CoV-2 infection. 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 protein7 and were optimised by AstraZeneca with half-life extension and reduction of Fc effector function. The half-life extension more than triples the durability of its action compared to conventional antibodies;8-10 data from the Phase III PROVENT trial show protection lasting at least six months.11 The reduced Fc effector function aims to minimise the risk of antibody-dependent enhancement of disease – a phenomenon in which virus-specific antibodies promote, rather than inhibit, infection and/or disease.12
Evusheld received Emergency Use Authorisation (EUA) in the US in December 2021 for the pre-exposure prophylaxis (prevention) of COVID-19 in people 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, or have a history of severe adverse reactions to these vaccines. About 2% of the global population is considered at increased risk of an inadequate response to a COVID-19 vaccine.13,14
Evusheld is also authorised for use and being supplied in several other countries around the world.
The primary data supporting the Evusheld EUA are from the ongoing PROVENT Phase III pre-exposure prevention trial, which showed a statistically significant reduction (77% at primary analysis, 83% at median six-month analysis) in the risk of developing symptomatic COVID-19 compared to placebo, with protection from the virus continuing for at least six months.4 More follow-up is needed to establish the full duration of protection provided by Evusheld.
In October 2021, AstraZeneca announced positive high-level results from the TACKLE Phase III outpatient treatment trial in which a 600mg IM dose of Evusheld was generally well-tolerated.4 AstraZeneca is discussing the TACKLE mild-to-moderate COVID-19 treatment data with health authorities.
Evusheld was well-tolerated in the trials.
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 Defence; Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defence, under Contract No. W911QY-21-9-0001.
Under the terms of the licensing agreement with Vanderbilt, AstraZeneca will pay single-digit royalties on future net sales.
AstraZeneca
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.
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References
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2. Fajnzylber, J et al. SARS-CoV-2 viral load is associated with increased disease severity and mortality. Available at https://www.nature.com/articles/s41467-020-19057-5/ [Last accessed March 2022}
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4. FACT SHEET FOR HEALTHCARE PROVIDERS: EMERGENCY USE AUTHORIZATION FOR EVUSHELD™ (tixagevimab co-packaged with cilgavimab). Available at: https://www.fda.gov/media/154701/download [Last accessed: March 2022].
5. Zhou H, et al. Neutralization of SARS-CoV-2 Omicron BA.2 by Therapeutic Monoclonal Antibodies. Available at: https://www.biorxiv.org/content/10.1101/2022.02.15.480166v2.full.pdf [Last accessed March 2022].
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7. 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.
8. 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.
9. 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.
10. 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.
11. 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: March 2022].
12. van Erp EA, et al. Fc-mediated antibody effector functions during respiratory syncytial virus infection and disease. Front Immunol. 2019; 10: 548.
13. Harpaz 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.
14. AstraZeneca data on file.
Veeva ID: Z4-43091
Date of preparation: March 2022