FDA revises emergency use authorization for AstraZeneca's Evusheld prophylaxis treatment for COVID-19; revised regimen offers a higher dose due to evidence suggesting lower effectiveness against Omicron subvariants

WASHINGTON , February 25, 2022 (press release) –

The U.S. Food and Drug Administration has revised the emergency use authorization for Evusheld (tixagevimab co-packaged with cilgavimab) to change the initial dose for the authorized use as pre-exposure prophylaxis (prevention) of COVID-19 in certain adults and pediatric patients.

Based on the most recent information and data available, Evusheld may be less active against certain Omicron subvariants. The dosing regimen was revised because available data indicate that a higher dose of Evusheld may be more likely to prevent infection by the COVID-19 Omicron subvariants BA.1 and BA.1.1 than the originally authorized Evusheld dose.

Previously, the authorized Evusheld dosage was 150 mg of tixagevimab and 150 mg of cilgavimab administered as two separate consecutive intramuscular injections, with repeat doses every six months while SARS-CoV-2 remains in circulation. With this EUA revision, FDA has increased the initial authorized dose to 300 mg of tixagevimab and 300 mg of cilgavimab. Patients who have already received the previously authorized dose (150 mg of tixagevimab and 150 mg of cilgavimab) should receive an additional dose of 150 mg of tixagevimab and 150 mg of cilgavimab as soon as possible to raise their monoclonal antibody levels to those expected for patients receiving the higher dose.

Evusheld is authorized for the emergency use as pre-exposure prophylaxis (PrEP) for prevention of COVID-19 in certain adults and pediatric patients (12 years of age and older weighing at least 40 kg). Health care providers should only administer it to individuals who are not currently infected with SARS-CoV-2 and who have not had a known recent exposure to someone infected with SARS-CoV-2. Evusheld is only authorized for those:

• who have moderate-to-severe immune compromise due to a medical condition or who have received immunosuppressive medications or treatments and may not mount an adequate immune response to COVID-19 vaccination or
• for whom vaccination with any available approved or authorized COVID-19 vaccine 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).

The duration of protection provided by Evusheld against symptomatic SARS-CoV-2 infection may not be as long as was shown in the clinical trial supporting the initial authorization because the clinical trial data came from a time period before the emergence of the BA.1 and BA.1.1 subvariants. However, it is not known whether BA.1 and BA1.1 will still be circulating in the coming months or whether another Omicron subvariant, BA.2, for which Evusheld is expected to have greater neutralizing activity, will become dominant. Because it is unclear which SARS-CoV-2 variant or Omicron subvariant will become dominant in the United States over the next few months, the recommended timing for repeat dosing cannot be provided at this time. We will continue to monitor the situation closely and will provide updates with redosing recommendations in the near future when more data are available to determine the appropriate timing of redosing (e.g., 3 months or 6 months after the prior dose).

What should patients know:
Patients who previously received an initial lower dose of Evusheld (150 mg of tixagevimab and 150 mg of cilgavimab) should contact their health care provider and return for an additional 150 mg of tixagevimab and 150 mg of cilgavimab dose as soon as possible. Any subsequent repeat dosing will be timed from the date of this additional Evusheld dose.

Patients who have not received any doses of Evusheld should talk to their health care provider to determine whether, based on their individual circumstances, they are eligible to receive it. If they are eligible, they should receive the 300 mg of tixagevimab and 300 mg of cilgavimab dose.

Patients with any additional questions should contact their health care provider.
What health care professionals should know:
Health care professionals should contact patients who received the previously authorized Evusheld dose to return for an additional 150 mg tixagevimab and 150 mg cilgavimab dose as soon as possible.
The volume of each injection for the new, higher dose will be larger, 3 mL instead of 1.5 mL. This means that the injections should be limited to large muscles on the body that can accommodate this volume (e.g., the gluteal muscles).
Health care professionals should review the updated Fact Sheets and Dear Health Provider Letter for Evusheld.
As part of the EUA, FDA requires health care providers who prescribe Evusheld to report all medication errors and serious adverse events considered to be potentially related to Evusheld through FDA’s MedWatch Adverse Event Reporting program. Providers can complete and submit the report online; or download and complete the form, then submit it via fax at 1-800-FDA-0178.

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