Builds on initial US government agreement, now totalling 1.7 million doses
Only antibody therapy authorized in the US for pre-exposure prophylaxis of COVID-19 in people who are immunocompromised
AstraZeneca today announced the US Department of Health and Human Services has finalized its agreement to purchase an additional one million doses of EVUSHELDTM (150mg of tixagevimab co-packaged with 150mg of cilgavimab), a long-acting antibody combination for the pre-exposure prophylaxis (prevention) of COVID-19 in immunocompromised populations.
This agreement includes the 500,000 additional dose purchase announced by the US government on January 12, 2022 and follows the government’s initial agreement for the purchase of 700,000 doses of EVUSHELD which are already being administered at sites around the US, for a total of 1.7 million doses. The US government has indicated that it plans to distribute these additional doses to states and territories at no cost.
Ruud Dobber, Executive Vice President and President, BioPharmaceuticals Business Unit, AstraZeneca, said: “With continued cases of COVID-19 across the US and in the wake of the Omicron variant, there remains a critical need to provide additional protection to immunocompromised patients who are most vulnerable to the virus. We are proud to continue playing a leading role in the fight against COVID-19 with EVUSHELD, the first long-acting antibody combination to receive emergency use authorization in the US for pre-exposure prophylaxis of COVID-19 and the only antibody therapy authorized for this use that shows neutralizing activity against Omicron and all other variants of concern to date.”
Multiple independent live and pseudovirus studies showed that EVUSHELD retains neutralizing activity against the Omicron variant and all tested SARS-CoV-2 variants of concern to date.1-4 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 received Emergency Use Authorization (EUA) in the US on December 8, 2021 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 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.
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.
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.
The most common adverse events are headache, fatigue and cough.
Use in Specific Populations:
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.
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.
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.
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
o 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
o 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:
o For treatment of COVID-19, or
o 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.
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.
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. 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 protein5 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;6-8 data from the Phase III PROVENT trial show protection lasting at least six months.9 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.10 EVUSHELD is delivered as an IM dose of 150mg tixagevimab and 150mg cilgavimab administered in two separate, consecutive injections.
In December 2021, the FDA issued an EUA for the use of EVUSHELD for the pre-exposure prophylaxis (prevention) of COVID-19. It is the only antibody authorized in the US to prevent COVID-19 symptoms before virus exposure. EVUSHELD is also authorized for emergency use for prevention of COVID-19 in several other countries.
In August 2021, AstraZeneca announced that EVUSHELD demonstrated a statistically significant reduction in the risk of developing symptomatic COVID-19 in the PROVENT trial; efficacy was 83% compared to placebo in a six-month analysis announced on November 18, 2021. In October 2021, AstraZeneca announced positive high-level results from the EVUSHELD TACKLE Phase III outpatient treatment trial. EVUSHELD is also being studied as a potential treatment for hospitalized COVID-19 patients as part of the National Institute of Health’s ACTIV-3 trial and in an additional collaborator hospitalization treatment trial.
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.
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.
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1 ACTIV. 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: February 2022].
2 VanBlargan, L.A., Errico, J.M., Halfmann, P.J. et al. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies. Nat Med (2022). https://doi.org/10.1038/s41591-021-01678-y.
3 Dejnirattisai W, Huo J, Zhou D et al. SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses, Cell, Volume 185, Issue 3, 2022, Pages 467-484.e15,
ISSN 0092-8674, https://doi.org/10.1016/j.cell.2021.12.046.
4 Takashita E, Kinoshita N, Yamayoshi et al. Efficacy of Antibodies and Antiviral Drugs against Covid-19 Omicron Variant. N Engl J Med. 2022 Jan 26. doi: 10.1056/NEJMc2119407. Epub ahead of print. PMID: 35081300.
5 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.
6 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.
7 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.
8 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.
9 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].
10 van Erp EA, et al. Fc-mediated antibody effector functions during respiratory syncytial virus infection and disease. Front Immunol. 2019; 10: 548.