Evusheld: A New Monoclonal Antibody for Pre-Exposure Prophylaxis against COVID-19 in the Immunocompromised

A new tool has now entered the armamentarium of medical treatments in the fight against COVID-19: AZD7442, also known as Evusheld.

Evusheld is a long-acting monoclonal antibody combination that received Emergency Use Authorization (EUA) by the FDA for use as COVID-19 pre-exposure prophylaxis in adults and children at least 12 years old who do not have an adequate immune response to COVID-19 vaccination or cannot be fully vaccinated. Currently available therapies for COVID-19 acute infection include oral antiviral pills (such as Paxlovid) and monoclonal antibody infusions that can be used in the treatment of mild to moderate COVID-19 infection for patients at risk for developing more severe disease, such as the immunocompromised.  However, Evusheld is the first agent to receive EUA for pre-exposure prophylaxis (PrEP).

AZD7442 (Evusheld) is a combination of two long-acting monoclonal antibodies, tixagevimab and cilgavimab, administered as two intramuscular injections.  The injections have been authorized for (1) those with a medical condition or immunosuppressive medications that result in a moderate to severely compromised immune system that may not respond adequately to the COVID-19 vaccination and (2) those with severe allergic or adverse reactions to the COVID-19 vaccine or its components and cannot get fully vaccinated.1  Evusheld used a combination of these monoclonal antibodies that were derived from B-cells donated by convalescent patients after SARS-CoV-2 viral infection.

Data used to support the EUA for Evusheld came from PROVENT, a Phase III, randomized, double-blind, placebo-controlled trial assessing efficacy of a single 300 mg dose of AZD7442 compared to placebo as pre-exposure prophylaxis for prevention of COVID-19. Over 5000 participants across 87 sites in the US, UK, Spain, France and Belgium were enrolled. According to the press release from AstraZeneca, the study found AZD7442 reduced the risk of developing symptomatic COVID-19 by 77% (95% CI, 46 to 90), compared to placebo; there were no cases of severe COVID-19 or COVID-19 related deaths in those treated with AZD7442.2

While Evusheld offers promising protection against COVID-19, there are a few potential roadblocks to its future implementation. The United States federal government has obtained 700,000 doses of Evusheld to date,3 which will not cover all the immunocompromised individuals in the United States. Evusheld efficacy against Omicron or other potential future variants is also unknown.

Dr. Rebecca Sadun, Assistant Professor of Medicine and Pediatrics in the Divisions of Rheumatology at Duke University School of Medicine, was involved in the determination of Evusheld distribution for immunocompromised patients in rheumatology. Given limited supply, doses available to rheumatology were not enough to account for even 10% of their immunocompromised patients, she said.

“Given that immune compromise is a spectrum, an interdisciplinary team of leaders at our institution created a tiered system for prioritizing the most immune suppressed, starting with those who are on B-cell suppressing depleting therapies, and then continuing down to account for all of the categories of immunocompromised,” Sadun explained. “As we receive additional doses, we look forward to offering it to more and more qualifying individuals.”

Ultimately, immunocompromised patients may not receive full protection from COVID-19 vaccination and have an incomplete or absent ability to mount an immune response. Thus, pre-exposure prophylaxis through monoclonal antibodies like Evusheld offer a novel mechanism to help reduce severity of COVID-19 infection in the immunocompromised, particularly those who do not generate an adequate immune response to the COVID-19 vaccines.

References

1. FDA FACT SHEET FOR HEALTHCARE PROVIDERS: EMERGENCY USE AUTHORIZATION FOR EVUSHELD. Source: https://www.fda.gov/media/154701/download

2. AstraZeneca Press Release, 20 August 2021. Source: https://www.astrazeneca.com/media-centre/press-releases/2021/azd7442-prophylaxis-trial-met-primary-endpoint.html

3. AstraZeneca, 8 December 2021. Source: https://www.astrazeneca.com/media-centre/press-releases/2021/evusheld-long-acting-antibody-combination-authorised-for-emergency-use-in-the-us-for-pre-exposure-prophylaxis-prevention-of-covid-19.html