EUA of Monoclonal Antibodies Revoked: Are Oral COVID Drugs the Only Hope?

Sotrovimab, a new COVID-19 monoclonal antibody drug from GlaxoSmithKline (GSK) and Vir Biotechnology (Vir), was granted Emergency Use Authorization (EUA) by the FDA in May 2021, making it the third new monoclonal antibody therapy approved in the United States.

However, less than a year after authorization was granted, on April 5, 2022, the FDA announced that the authorization for sotrovimab was revoked in response to a new variant of Omicron, BA.2, which had climbed to account for more than 50% of confirmed cases in the U.S. The decision to cancel the therapeutic approval of sotrovimab was prompted by available clinical data showing that it was not effective in neutralizing the BA.2 variant. 

Sotrovimab Proved Effective Against Alpha, Beta, and Gamma Variants

Sotrovimab was approved in May 2021 for treating COVID patients over 12 years of age with mild to moderate symptoms and those at risk of developing severe disease. It is administered by intravenous injection. The trial results submitted by GlaxoSmithKline and Vir confirmed that sotrovimab was effective against Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) variants, which were prevalent at the time.

However, with the emergence of new strains of Omicron and the BA.2 subvariant, the FDA has taken steps to limit the use of sotrovimab, and has stopped using it in New Jersey, Massachusetts, Arizona, Illinois, and other areas where BA.2 is prevalent since March. The FDA even announced a complete suspension of the use of sotrovimab throughout the United States on April 5. 

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Monoclonal Antibodies Fail to Protect Against Omicron Variants

The proliferation of Omicron variants in recent months has prompted the FDA to evaluate the efficacy of approved new drugs for COVID-19 on a rolling basis. Sotrovimab is not the first antibody drug to have its authorization revoked.

In January, the FDA also announced revised restrictions on the use of two monoclonal antibody regimens: Eli Lilly’s antibody cocktail therapy using Bamlanivimab and Etesevimab, and Regeneron’s REGEN-COV (casirivimab and imdevimab, administered together).

The FDA pointed out that monoclonal antibodies are laboratory-generated protein drugs whose efficacy will diminish as the viral structures evolve. Given that these monoclonal antibodies were ineffective against Omicron, a ban on the use of both monoclonal antibody drugs from Eli Lilly and Regeneron in all U.S. states was announced in January.

Updates on Existing Oral Drugs for COVID-19

Following the FDA’s withdrawal of approval for several monoclonal antibodies, the mainstream treatment options are now mostly oral drugs treating mild to moderate COVID-19, including Paxlovid from Pfizer, molnupiravir from MSD (Merck in the US and Canada), and remdesivir from Gilead.

However, oral drugs have not been proven to be able to protect completely against SARS-CoV-2 variants. For example, the advisory committee on molnupiravir has suggested that the drug has the potential to interfere with the genetic replication of the virus, leading to the risk of causing unexpected mutations. At this stage, MSD is required to submit the viral genome database to the FDA on a monthly basis to monitor the effect of its drug on virus variants.

In addition, a recent European study sponsored by the European Commission, which recruited more than 800 subjects from five European countries, showed that remdesivir did not significantly improve the treatment outcomes of critically ill patients requiring oxygen support compared to the control group. Remdesivir received its approval back in 2020, and this result may also lead to adjustments in its use by the European Medicines Agency (EMA).

Written by Kathy Huang/ Translated by Richard Chau

Author

GeneOnline Team