Evusheld, the only FDA-approved COVID-19 pre-exposure prophylactic, is anticipated to be ineffective against the emerging XBB.1.5 variant.
The emergence of XBB.1.5, the infectious Omicron subvariant, raises concerns once again about the inability of monoclonal antibodies to neutralize the newest COVID-19 iterations.
Now, the US Food and Drug Administration (FDA) has released a statement saying they anticipate Evusheld will not effectively neutralize XBB.1.5.
AstraZeneca’s Evusheld (tixagevimab and cilgavimab) is a dual injectable, previously FDA-approved for the early outpatient treatment of mild-to-moderate COVID-19 disease. Evusheld is the only approved option for pre-exposure prophylaxis (PrEP) of COVID-19.
The Centers for Disease Control and Prevention (CDC) estimates XBB.1.5 is now responsible for 27.6% of COVID-19 infections in the US. Because the similar XBB variant was not neutralized by Evusheld, the FDA has reason to believe the treatment will also be ineffective against XBB1.5.
The FDA has a history of pausing the distribution of monoclonal antibodies when they have been proven ineffective against the latest COVID-19 mutations. The agency has not yet taken this step, and will provide more updates upon receipt of additional data verifying Evusheld inactivity.
Evusheld was granted Emergency Use Authorization (EUA) by the FDA for the prevention of COVID-19 infection in moderately-to-severely immunocompromised adults and children, 12 years and older and weighing at least 40 kg, who were not currently positive for COVID-19 and had not had a recent exposure.
Tixagevimab and cilgavimab, Evusheld’s long-acting antibody combination, are both human monoclonal antibodies derived from B-cells donated by recovered COVID-19 patients.
A prior clinical study found that Evusheld reduced the risk of severe or fatal COVID-19 disease progression by 50%. Participants given Evusheld within 3 days of symptom onset saw an 88% reduction in severe or fatal COVID-19. Within 5 days of symptom onset, Evusheld was 67% more effective than placebo at preventing severe or fatal COVID-19.
The FDA had already upped the recommended dosage of Evusheld in February 2022 to help the treatment retain some efficacy against the Omicron BA.1 and BA.1.1 variants.
The FDA noted they are closely monitoring the emergence of XBB.1.5 and stated approved COVID-19 prophylactics and treatments, including Evusheld, are still recommended for the time being.