Those with severe adverse reactions to COVID-19 vaccine or the inability to mount an adequate immune response after receiving one now have another option to protect themselves against SARS-CoV-2.

The FDA issued an Emergency Use Authorization (EUA) for AstraZeneca's Evusheld (tixagevimab copackaged with cilgavimab and administered together) for the preexposure prophylaxis of COVID-19 in certain adults and children aged 12 years or older and weighing at least 40 kg (approximately 88 pounds).

"The product is only authorized for those individuals who are not currently infected with the SARS-CoV-2 virus and who have not recently been exposed to an individual infected with SARS-CoV-2," the FDA advises.

Those prescribed the product also must be either:

• Moderate to severely compromised immune systems due to a medical condition or taking immunosuppressive medications or treatments, and may not mount an adequate immune response to COVID-19 vaccination (examples of such medical conditions or treatments can be found in the fact sheet for healthcare providers) or;
• Have a history of severe adverse reactions to a COVID-19 vaccine and/or component(s) of those vaccines; therefore, vaccination with a COVID-19 vaccine, according to the approved or authorized schedule, is not recommended

Medical conditions or treatments that may result in moderate-to-severe immune compromission and an inadequate immune response to COVID-19 vaccination include, but are not limited to:

• Active treatment for solid tumor and hematologic malignancies
• Receipt of solid-organ transplant and taking immunosuppressive therapy
• Receipt of chimeric antigen receptor T-cell or hematopoietic stem cell transplant (within 2 years of transplantation or taking immunosuppression therapy)
• Moderate or severe primary immunodeficiency (e.g., DiGeorge syndrome, Wiskott-Aldrich syndrome)
• Advanced or untreated HIV infection (people with HIV and CD4 cell counts).

"Vaccines have proven to be the best defense available against COVID-19. However, there are certain immune compromised individuals who may not mount an adequate immune response to COVID-19 vaccination, or those who have a history of severe adverse reactions to a COVID-19 vaccine and therefore cannot receive one and need an alternative prevention option," said Patrizia Cavazzoni, MD, director of the FDA Center for Drug Evaluation and Research. "Today's action authorizes the use of the combination of two monoclonal antibodies to reduce the risk of developing COVID-19 in these individuals."

In granting the EUA, the FDA states that one dose of Evusheld, administered as two separate consecutive intramuscular injections—one injection per monoclonal antibody, given in immediate succession—might be effective for preexposure prevention for 6 months. It emphasizes that Evusheld is not authorized for the treatment of COVID-19 or for postexposure prevention of COVID-19.

Public health officials also strongly state that preexposure prevention with Evusheld is not a substitute for vaccination in people for whom COVID-19 vaccination is recommended. They still urge vaccinations for those who do not have serious reactions and can mount an antibody response.

Tixagevimab and cilgavimab are long-acting monoclonal antibodies, laboratory-made proteins that mimic the immune system's ability to fight off harmful pathogens that are specifically directed against the spike protein of SARS-CoV-2 and are designed to block the virus' attachment and entry into human cells. Tixagevimab and cilgavimab bind to different, nonoverlapping sites on the spike protein of the virus.

PROVENT, a randomized, double-blind, placebo-controlled clinical trial, was the primary support for the granting of an EUA, according to the FDA. Participants in that study were adults greater than age 59 years, with a prespecified chronic medical condition, or at increased risk of SARS-CoV-2 infection for other reasons who had not received a COVID-19 vaccine and did not have a history of SARS-CoV-2 infection or test positive for SARS-CoV-2 infection at the start of the trial. The primary outcome was defined as whether a trial participant had a first case of COVID-19 after receiving Evusheld or placebo and before Day 183 of the trial.

In the trial, 3,441 people received Evusheld and 1,731 received a placebo, with a 77% reduced risk of developing COVID-19 in recipients compared with those who received a placebo—a statistically significant difference. Additional analysis found the reduction in risk of developing COVID-19 was maintained for 6 months. The safety and effectiveness of Evusheld for use in the pre-exposure prevention of COVID-19 continues to be evaluated.

Possible side effects of Evusheld include hypersensitivity reactions (including anaphylaxis), bleeding at the injection site, headache, fatigue, and cough.

While serious cardiac adverse events were infrequent in PROVENT, more trial participants had serious cardiac adverse events (such as myocardial infarction and heart failure) after receiving Evusheld compared with placebo. However, it is not clear if the cardiac adverse events were caused by the drug, according to the FDA, and all the participants who had the events had either risk factors for cardiac disease or a history of cardiovascular disease before participating in the clinical trial.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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