Evusheld: A pre-exposure treatment for prevention of COVID-19 in high-risk individuals
Remember: treatment is NOT a substitute for vaccination
4 minute read
Evusheld, made by AstraZeneca, is a monoclonal antibody treatment used for pre-exposure prophylaxis of COVID-19 that is authorized in the US, Canada, and Europe. This means that this treatment can be administered to individuals at high risk for illness before they’ve been exposed to SARS-CoV-2 or have developed illness.
A dose of Evusheld is composed of lab-created proteins tixagevimab and cilgavimab, which are each administered in an intramuscular injection, one immediately after the other. These antibodies, derived from antibodies from B cells of infected individuals, target the spike proteins of SARS-CoV-2 and help the immune system to neutralize the virus. Modifications were made in order to extend the antibodies’ half-life in order to increase the durability and longevity of the protection offered.
The Phase III randomized clinical trial of Evusheld began in November 2020 and was conducted across 87 sites in more than 5 countries. It included over 5000 unvaccinated participants, adults over 18 years old, who either were more considered to be more vulnerable to infection or who had an increased risk of exposure to SARS-CoV-2 (e.g., occupation). This study sample was representative of persons who are immunocompromised, older than 60 years old, and/or with preexisting medical conditions. Notably, individuals who were medically unable to be vaccinated were also included in this study. The Phase III study had two major endpoints to evaluate safety and efficacy: incidence of adverse events and symptomatic COVID-19 infection, respectively. Roughly two-thirds of the participants were assigned to the Evusheld treatment group, and the remaining third of the participants received a placebo. The study was double-blinded, so participants were not aware of which treatment they received.
Ultimately, the results indicate that the treatment was well-tolerated and reduced the relative risk of COVID-19 infection (confirmed by positive PCR test) by approximately 77 percent. When the follow-up time was extended and evaluated after six months, that reduction increased to roughly 83 percent. At six months after administration, the antibody levels in serum were still elevated compared to baseline, suggesting that the protection may last at least that long, but more research is necessary. These preliminary results are in accordance with previously published data
The primary endpoints for evaluation were completed in May 2021, by which investigators were able to release the data for primary analysis, which was published in late April 2022. However, this trial is still ongoing and is expected to be completed around July of this year.
Evusheld is meant to be used before an individual is exposed or becomes ill from COVID-19 infection. In other words, it may not be helpful as a treatment once a patient has tested positive or been in close contact with someone who has tested positive. Evusheld is authorized for use in adults and pediatric patients who are at least 12 years old and who weigh over 40kg. The drug is intended for individuals who have either compromised immune systems or a history of severe reactions to COVID-19 vaccines.
This treatment received its Emergency Use Authorization (EUA) from the U.S. FDA on December 8, 2021, allowing the drug to be used on a national scale to those who qualify. Due to the nature of monoclonal antibodies and their mechanism of action, there were and are still ongoing questions as to the effectiveness of the drug in response to other variants, including Omicron.
On February 24, 2022, the FDA revised the initial EUA to recommend doubling the dose. This higher dose of 300mg was found to offer increased protection against certain subvariants, including BA.1 and BA.1.1 compared to the original dose of 150 mg. Individuals who initially received the lower dose are encouraged to receive a second lower dose (150mg) in order to adhere to the new revised guidelines and be better protected against Omicron and other variants. With the potential threat of the BA.2 subvariant, it is notable that the protection from Evusheld is expected to be more effective against BA.2 than it is for BA.1 and BA.1.1, but more research is necessary to confirm this relationship. Evusheld was authorized in Europe as of late March and Canada as of April 2022.
Experts emphasize that while this drug is used to prevent COVID-19 infection among those for whom vaccination may not be sufficient, it is not a substitution for COVID-19 vaccination, which is still recommended to all who are eligible. For those individuals who receive a COVID-19 vaccine, it is recommended that they wait to receive Evusheld until at least two weeks post vaccination, as the monoclonal antibodies may affect the body’s immune reaction to the vaccine.
This treatment is one medical tool of many that have been authorized to prevent severe illness from COVID-19, particularly among those who need it most. Its use is still being studied and the protection provided will likely depend on future trends and variants.
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