AstraZeneca, Regeneron Say Their COVID-19 Antibodies Treatments Still Work on Omicron

Regeneron and AstraZeneca both say their therapeutic antibody cocktails remain active against Omicron, but questions remain in light of a Chinese study concluding that the variant escapes 85 percent of tested antibodies.

AstraZeneca posted laboratory results showing that its Evusheld (tixagevimab and cilgavimab) retained neutralization power similar to that found in a person previously infected with COVID-19. The study was performed independently by the FDA’s Center for Biologics Evaluation and Research, the company noted.

Regeneron did not provide detailed data, saying “Currently authorized REGEN-COV (casirivimab and imdevimab) antibodies have diminished potency vs. Omicron but are active against the predominant Delta variant.”

However, the company said the combo “maintained an adequate potency when tested on Omicron samples,” according to new preclinical data.

Both companies cited the “Open Data Portal SARS-CoV-2 Variants and Therapeutics Activity Explorer” hosted by the National Center for Advancing Translational Science (NCATS). The website contains detailed data on COVID-19 vaccines, antibodies and therapeutics and their potency against all 15 variants of the SARS-CoV-2 virus.

The NCATS site notes that the datasets “are intended to provide an at-a-glance summary of the in vitro activity of therapeutics against individual SARS-CoV-2 variants and reference strains” and should not be regarded as conclusive or reported in the media as established information. The data are all lab studies and have not been shown to correlate with clinical outcomes, it added; nevertheless, these are the data upon which Regeneron and AstraZeneca based their statements to the media.

Honing in on the Omicron variant (B.1.1.159) allows users to explore the potency windows. The constituent antibodies of each cocktail are listed separately. Clicking on the data point allows users to open a dataset browser with details. The potency changes are relative to the antibodies’ effect on the original Wuhan strain.

A Chinese study posted Dec. 9 on BioRxiv by a team from Peking University looked at all four antibodies. It’s important to note that this study, like all preprint studies, has not been peer-reviewed. The investigators determined that both of Regeneron’s antibodies, casirivimab and imdevimab, are 2,000-fold less potent against Omicron. AstraZeneca’s cilgavimab was 1,000-fold less potent and tixagevimab was 6,860-fold less potent.

A National Institutes of Health study also looked at the AstraZeneca antibodies and found much less loss of potency: a 133-fold decrease for cilgavimab to 975-fold decrease for tixagevimab.

Yunlong Cao lead the Chinese study, which tested 247 human neutralizing antibodies obtained from convalescents and vaccinated people. The Regeneron and AstraZeneca cocktails were among many that showed severely diminished efficacy against Omicron.

Cao also found that Omicron escaped Lilly’s bamlanivimab/etesevimab combo and BRII-196, GlaxoSmithKline’s sotrovimab and DXP-604, an antibody by BeiGene/Singlomics, still functioned at reduced efficacy.

The most potent antibodies tested were those that directly interfered with Omicron’s ability to bind to the ACE2 receptor, the team wrote. However, “the neutralizing powers of these [antibodies] are often abrogated by receptor-binding domain mutations in the evolutionary arms race between SARS CoV-2 and human humoral immunity.”

Omicron’s spike protein has 30 mutations compared to the original Wuhan strain; 15 of those are in the receptor-binding domain, according to the Centers for Disease Control.

Access the NCATS OpenData Portal here: bit.ly/3yAnX74.

Read the Cao paper here: bit.ly/32dIsKq. — Michele G. Sullivan