Losing Options for COVID-19: Monoclonal Antibodies vs Omicron Subvariants

Volume 21, Issue 4

In July of this year, I authored a column updating the landscape of available treatments for BA.5, which had become the dominant strain of COVID-19 in the United States. Unfortunately, 2 new subvariants, BQ.1 and BQ.1.1, have recently supplanted BA.5 as the dominant strains in this country.

In my July column, I closed by saying, “Given the spike protein of the SARS-CoV-2 virus is the main site of mutation for this virus, it would make sense for pharmaceutical manufacturers to develop future products that do not depend so heavily on effective binding to the spike protein for viral neutralization.”

Those words appear prescient today, as we still depend heavily on monoclonal antibody products for treating and preventing COVID-19 infection, which is salient given the virus has again mutated its spike protein in the latest iteration of BQ.1 and BQ.1.1. In this week’s issue of Talking Therapeutics, we explore how the landscape of COVID-19 monoclonal antibodies has shifted again with these latest mutations.

Bebtelovimab Is Off the Table

As I discussed in my July column, bebtelovimab was the only monoclonal antibody to retain efficacy against BA.4 and BA.5, which made it the only viable monoclonal option for treating patients with COVID-19.

Unfortunately, the US Food and Drug Administration reported earlier this month through updated information in the package insert that bebtelovimab has lost its neutralizing effect against the BQ.1 and BQ.1.1 lineages. As such, we no longer have an effective monoclonal antibody product for treating COVID-19.

Fortunately, the available evidence suggests the efficacy of Paxlovid, remdesivir, and molnupiravir is preserved, so these agents can be recommended for treating patients with COVID-19 infection. According to the current National Institutes of Health treatment guidelines, Paxlovid and remdesivir are preferred agents, whereas molnupiravir is a second-line agent.

Evusheld Is Off the Table

Tixagevimab plus cilgavimab (Evusheld) is the only pre-exposure prophylactic agent available on the US market for COVID-19. While this important agent retained some neutralizing efficacy against the BA.4 and BA.5 lineages, recent evidence suggests it has lost efficacy against BQ.1 and BQ.1.1.

As such, this agent cannot be recommended for pre-exposure prophylaxis in regions where these 2 new variants are dominant.