AstraZeneca's Evusheld loses potency against new omicron subvariant, FDA warns

For COVID-19 antibody drugs in the pandemic world, it’s been life in the fast lane.

With the coronavirus rapidly evolving, there is little longevity for finely tuned antibodies. It was that way for successful but short-lived treatments from Regeneron, GSK and Eli Lilly. Now, for AstraZeneca’s Evusheld, the lights may be turning red.

Monday, amid reports that the antibody combo is ineffective against the latest subvariant of omicron, BA.4.6, the FDA has updated (PDF) its fact sheet for Evusheld, including a table detailing which geographic areas around the world present more risk of infection for Evusheld users.

With BA.4.6 spreading in the U.S. and beginning to take hold in Europe, Evusheld’s days as an option for prevention of infection could be numbered.

The BA.5 subvariant is still the dominant version of the coronavirus globally, accounting for 85% of current infections, an AstraZeneca spokesman pointed out. The company also adds that BA.4.6 represents just 6.2% of infections around the world and is “growing slowly.”

“It is not expected to become a dominant strain,” the spokesperson wrote in an email. “Based on the low prevalence of BA.4.6 and Evusheld’s activity against the dominant variant, Evusheld should continue to provide protection to the vast majority of intended recipients.”

The potential spread of the BA.4.6 subvariant is bad news for those who are immunocompromised and don’t get an effective response from vaccines. For these people, Evusheld has been billed as an effective option.

The FDA still recommends the use of Evusheld—which is a combination of separately packaged drugs tixagevimab and cilgavimab—but warns of the increased risk of contracting COVID variants not neutralized by the combo.

One antibody treatment that remains on the market is Lilly's bebtelovimab. While it doesn’t have authorization for prophylactic use, it can be used to treat mild-to-moderate COVID-19 in those who are at high risk for progression to a severe form of the virus. 

After a brief run of success, Lilly's bamlanivimab/etesevimab antibody combo was sidelined by the FDA earlier this year. Also meeting the same fate were Regeneron's Regen-Cov and GSK and Vir Biotechnology's sotrovimab.  

Early last month, Columbia University Professor David Ho, Ph.D., found in lab testing that the BA.4.6 lineage evaded the neutralization ability of Evusheld.

“The COVID-19 variant landscape is dynamic and location dependent, with different variants and subvariants coming and going, with only a few becoming dominant,” AstraZeneca’s spokesperson said. “Variants are rarely dominant for more than a few months—they tend to either evolve further into different subvariants or are replaced by newer variants.”

Editor's note: This story was edited to reflect that Eli Lilly's bebtelovimab remains on the market to treat mild to moderate COVID-19.