Only antibody authorized in the US for pre-exposure prophylaxis of COVID-19

AstraZeneca’s EVUSHELD (tixagevimab co-packaged with cilgavimab), a long-acting antibody combination for the prevention of COVID-19, retained neutralizing activity against the Omicron SARS-CoV-2 variant (B.1.1.529), according to new preclinical data.

In this study, EVUSHELD’s Inhibitory Concentration 50 (IC50), a measure of neutralizing potency of an antibody, was 171 ng/ml and 277 ng/ml in two confirmatory tests, which is within the range of neutralizing titers found in someone who has been previously infected with COVID-19. EVUSHELD’s IC50 for the original strain of SARS-CoV-2, previously referred to as the Wuhan strain, was approximately 1.3 ng/ml and 1.5 ng/ml, respectively.

The early data, generated by pseudovirus testing of the full Omicron variant spike against the combination of tixagevimab with cilgavimab, the antibodies that comprise EVUSHELD, add to the growing body of preclinical evidence demonstrating that EVUSHELD retains activity against all tested variants of concern to date.¹

The study was performed independently by investigators at the US Food and Drug Administration (FDA), Center for Biologics Evaluation and Research. The work was supported by US government research funds.

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “This study shows EVUSHELD retains neutralization activity against the Omicron variant. By combining two 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 the first long-acting antibody to receive emergency use authorization in the US for pre-exposure prophylaxis of COVID-19, in addition to authorizations in other countries, and we are working with regulators on applications for the use of EVUSHELD in treating COVID-19.”

The Omicron variant was not in circulation during the EVUSHELD clinical trials. The Company is continuing to collect further data to better understand the implications of this observation in clinical practice. Additional analyses to evaluate EVUSHELD against the Omicron variant are being conducted by AstraZeneca and third-party laboratories, with data anticipated very soon.

EVUSHELD received Emergency Use Authorization (EUA) in the US in December 2021 for 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. The first doses are expected to become available within days.

About 2% of the global population is considered at increased risk of an inadequate response to a COVID-19 vaccine.^3,4 Emerging evidence indicates that protecting vulnerable populations from getting COVID-19 could help prevent viral evolution that is an important factor in the emergence of variants.⁵

Additionally, the TACKLE Phase III outpatient treatment trial of EVUSHELD showed it reduced the risk of developing severe COVID-19 or death (from any cause) by 50% compared to placebo in non-hospitalized patients with mild to moderate COVID-19 who had been symptomatic for seven days or less.⁶

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 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 protein⁷ 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;^8-10 data from the Phase III PROVENT trial show protection lasting at least six months.¹¹ 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.¹²

In December 2021, the U.S. Food and Drug Administration issued an Emergency Use Authorization (EUA) for the use of EVUSHELD (tixagevimab co-packaged with cilgavimab) 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.

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

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