WILMINGTON, Del.--(BUSINESS WIRE)-- New preclinical authentic ‘live’ virus data from Washington University School of Medicine demonstrated that EVUSHELD^TM (tixagevimab co-packaged with cilgavimab) retains potent neutralizing 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 neutralizing 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 neutralization 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 neutralizes 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 authorized 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.

EVUSHELD is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of EVUSHELD under Section 564(b)(1) of the Food, Drug and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

Visit EVUSHELD.com to learn more.

IMPORTANT SAFETY INFORMATION

EVUSHELD (tixagevimab co-packaged with cilgavimab) has not been approved, but has been granted an Emergency Use Authorization (EUA) by FDA. There are limited clinical data available and serious and unexpected adverse events may occur that have not been previously reported with EVUSHELD use.

Contraindication:

EVUSHELD is contraindicated in individuals with previous severe hypersensitivity reactions, including anaphylaxis, to any component of EVUSHELD.

Warnings and Precautions:

Hypersensitivity Including Anaphylaxis
Serious hypersensitivity reactions, including anaphylaxis, have been observed with IgG1 monoclonal antibodies like EVUSHELD. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive therapy. Clinically monitor individuals after injections and observe for at least 1 hour.

Clinically Significant Bleeding Disorders
As with any other intramuscular injection, EVUSHELD should be given with caution to individuals with thrombocytopenia or any coagulation disorder.

Cardiovascular Events
A higher proportion of subjects who received EVUSHELD versus placebo reported myocardial infarction and cardiac failure serious adverse events. All of the subjects with events had cardiac risk factors and/or a prior history of cardiovascular disease at baseline. A causal relationship between EVUSHELD and these events has not been established. Consider the risks and benefits prior to initiating EVUSHELD in individuals at high risk for cardiovascular events, and advise individuals to seek immediate medical attention if they experience any signs or symptoms suggestive of a cardiovascular event.

Adverse Reactions:

The most common adverse events are headache, fatigue and cough.

Use in Specific Populations:

Pregnancy
There are insufficient data to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. EVUSHELD should only be used during pregnancy if the potential benefit outweighs the potential risk for the mother and the fetus.

Lactation
There are no available data on the presence of tixagevimab or cilgavimab in human milk or animal milk, the effects on the breastfed infant, or the effects of the drug on milk production. Maternal IgG is known to be present in human milk.

Pediatric Use
EVUSHELD is not authorized for use in pediatric individuals under 12 years of age or weighing less than 40 kg. The safety and effectiveness of EVUSHELD have not been established in pediatric individuals.

AUTHORIZED USE

EVUSHELD (tixagevimab co-packaged with cilgavimab) is authorized for use under an EUA for the pre-exposure prophylaxis of COVID-19 in adults and pediatric individuals (12 years of age and older weighing at least 40 kg):

• Who are not currently infected with SARS-CoV-2 and who have not had a known recent exposure to an individual infected with SARS-CoV-2 and
  • Who have moderate to severe immune compromise due to a medical condition or receipt of immunosuppressive medications or treatments and may not mount an adequate immune response to COVID-19 vaccination or
  • For whom vaccination with any available COVID-19 vaccine, according to the approved or authorized schedule, is not recommended due to a history of severe adverse reaction (e.g., severe allergic reaction) to a COVID-19 vaccine(s) and/or COVID-19 vaccine component(s).

EVUSHELD has been authorized by FDA for the emergency use described above. EVUSHELD is not FDA-approved for any use, including use for pre-exposure prophylaxis of COVID-19.

EVUSHELD is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of EVUSHELD under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

LIMITATIONS OF AUTHORIZED USE

• EVUSHELD is not authorized for use in individuals:
  • For treatment of COVID-19, or
  • For post-exposure prophylaxis of COVID-19 in individuals who have been exposed to someone infected with SARS-CoV-2
• Pre-exposure prophylaxis with EVUSHELD is not a substitute for vaccination in individuals for whom COVID-19 vaccination is recommended. Individuals for whom COVID-19 vaccination is recommended, including individuals with moderate to severe immune compromise who may derive benefit from COVID-19 vaccination, should receive COVID-19 vaccination
• In individuals who have received a COVID-19 vaccine, EVUSHELD should be administered at least two weeks after vaccination

See Full Fact Sheet for Healthcare Providers for examples of medical conditions or treatments that may result in moderate to severe immune compromise and an inadequate immune response to COVID-19 vaccination, the justification for emergency use of drugs during the COVID-19 pandemic, information on available alternatives, and additional information on COVID-19.

The FDA Letter of Authorization is available for reference, as well as the Fact Sheet for Patients, Parents And Caregivers.

SARS-CoV-2 Viral Variant

There is a potential risk of treatment failure due to the development of viral variants that are resistant to tixagevimab and cilgavimab administered together. Prescribing healthcare providers should consider the prevalence of SARS-CoV-2 variants in their area, where data are available, when considering prophylactic treatment options.

Reporting Adverse Events

The prescribing healthcare provider and/or your designee must report all SERIOUS ADVERSE EVENTS and MEDICATION ERRORS potentially related to EVUSHELD within 7 calendar days from the healthcare provider’s awareness of the event (1) by submitting FDA Form 3500 online, (2) by downloading FDA Form 3500 and then submitting by mail or fax, or (3) contacting the FDA at 1-800-FDA-1088 to request this form.

In addition, please fax a copy of all FDA MedWatch forms to AstraZeneca at 1-866-742-7984.

Report adverse events by visiting https://contactazmedical.astrazeneca.com, or calling AstraZeneca at 1-800-236-9933.

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 optimized 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 minimize 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 Authorization (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 authorized 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 Defense; Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, 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.

About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization 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. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

References

1. Case, J et al. Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains. Available at https://www.biorxiv.org/content/10.1101/2022.03.17.484787v1 [Last accessed March 2022]
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}
3. Su Y, et al. Multiple early factors anticipate post-acute COVID-19 sequelae. Cell. 2022;185(5):881-895.e20.
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].
6. World Health Organization. Weekly epidemiological update on COVID-19 - 22 February 2022. Available from: https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---22-february-2022 [Last accessed: March 2022].
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.

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