Evusheld

Authorized Use

Evusheld was authorized for emergency use as pre-exposure prophylaxis to help prevent COVID-19 in adults and children 12 years of age and older who weigh at least 88 pounds (40 kg). It was designed for individuals who are not currently infected with the virus and have not recently been exposed to someone with the infection.

This medication was primarily intended for two groups of people:

• Individuals with moderate to severe immune system impairment who may not produce an adequate immune response to COVID-19 vaccination. This includes people with certain medical conditions or those taking medications that suppress the immune system.
• Individuals for whom COVID-19 vaccination is not recommended due to a history of severe adverse reactions to the vaccine or its ingredients.

Current Authorization Status

The U.S. Food and Drug Administration (FDA) has announced that Evusheld is not currently authorized for use in the United States. Data indicates that the medication is unlikely to be effective against the SARS-CoV-2 variants that are currently circulating. The FDA may authorize its use again in the future if different variants that are susceptible to the drug become more common.

Important Limitations

Evusheld is not used for the following purposes:

• Treatment of an active COVID-19 infection.
• Prevention of COVID-19 after a known exposure to the virus (post-exposure prophylaxis).
• As a substitute for vaccination in people who are able to receive the COVID-19 vaccine and are expected to have an adequate immune response.

Mechanism of Action

Evusheld consists of two long-acting monoclonal antibodies, tixagevimab and cilgavimab. These are proteins designed in a laboratory to mimic the immune system's ability to fight off harmful pathogens like viruses.

The medication works through the following process:

• Targeting the Spike Protein: The antibodies specifically target the spike protein on the surface of the SARS-CoV-2 virus, which is the virus that causes COVID-19.
• Blocking Viral Entry: By binding to different, non-overlapping sites on the spike protein, the antibodies prevent the virus from attaching to human cells. This blocks the virus from entering the cells and replicating.
• Long-Lasting Protection: These antibodies have been modified to remain in the body for an extended period. This modification allows the medication to provide protection for several months after the initial administration.

Unlike a vaccine, which teaches the immune system to create its own antibodies, Evusheld provides ready-made antibodies directly to the body to help prevent infection before exposure occurs. However, the effectiveness of these antibodies can change as the virus evolves into new variants.

Common Side Effects

The most frequently reported side effects of Evusheld are generally mild and may include:

• Headache
• Fatigue
• Cough
• Nausea
• Injection site reactions, such as pain, redness, bruising, or swelling where the shots were administered

Serious Side Effects

In some cases, Evusheld can cause serious or life-threatening reactions. Seek immediate medical care if you experience any of the following:

• Allergic Reactions: Symptoms may include hives, rash, swelling of the face, lips, or throat, and difficulty breathing or swallowing.
• Cardiovascular Events: Some individuals in clinical trials experienced serious heart-related problems, including heart attack or heart failure. Symptoms to watch for include chest pain, shortness of breath, feeling faint, or sudden lightheadedness.

This is not a complete list of potential side effects. If you experience any unusual symptoms after receiving the medication, contact your healthcare provider.

Authorization Status

The FDA has revised the emergency use authorization for Evusheld, and it is not currently authorized for use in the United States. This is because the medication is unlikely to be effective against the most common circulating SARS-CoV-2 variants. Healthcare providers are advised to monitor local variant prevalence to determine if use becomes appropriate in the future.

Hypersensitivity and Allergic Reactions

Serious and potentially life-threatening allergic reactions, including anaphylaxis, have been reported with the use of monoclonal antibodies. If a clinically significant hypersensitivity reaction occurs, administration must be stopped immediately. Patients are typically monitored for at least one hour after receiving the injections to watch for immediate adverse reactions.

Cardiovascular Events

In clinical trials, a higher proportion of participants treated with Evusheld experienced serious cardiovascular adverse events compared to those in the placebo group. These events included heart attacks (myocardial infarction) and heart failure. Most participants who experienced these events had pre-existing risk factors or a history of cardiovascular disease. The risks and benefits should be carefully considered for individuals at high risk for cardiovascular events.

Bleeding Risk

Because Evusheld is administered as two separate intramuscular injections, caution is necessary for individuals with bleeding disorders or those taking anticoagulant medications (blood thinners). There is a risk of bleeding, bruising, or hematoma at the site of injection.

Pregnancy and Lactation

There is limited data on the use of Evusheld during pregnancy. It should only be used during pregnancy if the potential benefit to the patient outweighs the potential risk to the fetus. It is also unknown if the components of Evusheld pass into breast milk or how they might affect a nursing infant.

Pregnancy

There are no clinical studies or data available regarding the use of Evusheld in pregnant individuals. It is unknown if the medication increases the risk of birth defects, miscarriage, or other adverse outcomes for the mother or the fetus. Because Evusheld is composed of monoclonal antibodies, it is expected that the medication can cross the placenta and be transferred to the developing fetus.

Breastfeeding

It is not known whether the components of Evusheld pass into human breast milk. There is also no information available on how the medication might affect a nursing infant or the production of breast milk. If you are breastfeeding, you should consult with your healthcare provider to discuss the potential risks and benefits of receiving this treatment.

Consult Your Healthcare Provider

If you are pregnant, planning to become pregnant, or are breastfeeding, it is important to talk to your doctor. They can help determine if the potential benefits of the medication outweigh the unknown risks based on your individual health needs and the risk of COVID-19 exposure.

Available Forms

Evusheld is provided as a co-packaged product containing two separate monoclonal antibody medications. It is available in the following form:

• Injectable solution: Two separate vials containing sterile, preservative-free liquid for intramuscular administration.

The medication is administered by a healthcare provider as two separate, consecutive injections into the muscle, usually the buttocks.

Current Authorization Status

As of January 26, 2023, Evusheld is not currently authorized for emergency use in the United States. The U.S. Food and Drug Administration (FDA) removed the authorization because the medication is unlikely to be effective against the SARS-CoV-2 variants that are currently most common in the country.

Original Emergency Use Authorization

The FDA originally issued an Emergency Use Authorization (EUA) for Evusheld in December 2021. It was authorized for pre-exposure prophylaxis (prevention) of COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) who met specific criteria:

• Individuals with moderate to severe immune system impairment who might not have an adequate immune response to COVID-19 vaccination.
• Individuals for whom COVID-19 vaccination is not recommended due to a history of severe adverse reactions to the vaccine or its components.

Important Regulatory Limitations

Evusheld was never FDA-approved for any indication; it was only available under an EUA. It was not authorized for the treatment of COVID-19 or for use as a preventative measure after a person had already been exposed to the virus. The FDA emphasized that Evusheld is not a substitute for vaccination in people for whom COVID-19 vaccination is recommended.

The FDA continues to monitor the situation and may re-authorize the use of Evusheld if the prevalence of variants susceptible to the drug increases in the future. Healthcare facilities have been advised to retain their stock of the medication in case it becomes effective against future variants.

Prevention of COVID-19

Evusheld is a combination of two monoclonal antibodies, tixagevimab and cilgavimab, designed to prevent COVID-19. It was authorized for use in individuals who are unlikely to have an adequate immune response to COVID-19 vaccination or those for whom vaccination is not recommended due to a history of severe allergic reactions.

FDA Authorization Status

As of January 26, 2023, Evusheld is not authorized for emergency use in the United States. The FDA determined that the treatment is unlikely to protect against the SARS-CoV-2 variants that are currently most common. Because the virus changes over time, the antibodies in Evusheld may no longer be able to neutralize the circulating strains effectively.

Usage and Limitations

• Not a treatment: Evusheld is intended for pre-exposure prophylaxis (prevention) and is not authorized to treat individuals who already have COVID-19.
• Not a vaccine substitute: It is not a replacement for vaccination in people for whom COVID-19 vaccination is recommended.
• Eligibility: When authorized, it was restricted to adults and pediatric patients (12 years of age and older weighing at least 40 kg) with specific medical conditions or treatments that suppress the immune system.