Eli Lilly’s, Regeneron’s Monoclonal Antibodies May Need Tweaking for COVID-19 Variants

A new study has found that Eli Lilly and Regeneron may need to adjust their monoclonal antibody treatments to effectively fight fast-spreading COVID-19 variants, especially the South African mutation, which along with a UK variant has raised concerns among scientists that SARS-CoV-2 may mutate to resist vaccines and treatments.

Researchers are now expressing concern that should the virus continue to spread rapidly and undergo significant mutations, SARS-CoV-2 may need to be combated continually, perhaps annually, like influenza and stressed the importance of monitoring mutations globally and adjusting antibodies if needed.

The new study by researchers at Columbia University, the National Institutes of Health (NIH)  Vaccine Research Center and Regeneron tested Eli Lilly’s and Regeneron’s monoclonal antibodies against pseudoviruses the researchers created that contained each of the variants’ mutations as well as ones with all eight mutations of the UK variant and all nine of South Africa’s. Their findings, which have not yet been peer-reviewed, were posted on the bioRxiv preprint server.

The study found that Eli Lilly’s bamlanivimab (LY-CoV555) and Regeneron’s casirivimab (REGN10933), the former of which has been granted Emergency Use Authorization (EUA) by the FDA, were “completely or markedly abolished” by the South African variant but did not appear to be thwarted by the UK mutation. Eli Lilly’s bamlanivimab was found to be inactive against the South African strain, while Regeneron’s casirivimab was impaired.

Worse yet, they found that bamlanivimab, even when given with Junshi Biosciences’ CB6 antibody, failed to neutralize the South African strain.

However, Regeneron’s antibody cocktail REGN-COV2, which is comprised of imdevimab (REGN10987) and casirivimab and received an EUA for high-risk patients with moderate-to- severe COVID-19, was seemingly unaffected by the South African mutation.

The researchers also tested several monoclonal antibody candidates in development against the two strains, finding that a larger amount of them were significantly impacted by the South African variant than by the UK strain, which had only modest impacts on effectiveness.

“Mutationally, this virus is traveling in a direction that could ultimately lead to escape from our current therapeutic and prophylactic interventions directed to the viral spike,” they said.

Eli Lilly’s Chief Scientific Officer Dan Skovronsky said last week that the company has antibodies in its laboratories able to neutralize the South African mutation that it can advance if the variant is deemed a true global threat. And Regeneron said it has hundreds of neutralizing antibodies in its labs that could be combined as treatments against future variants.

A new Brazilian variant, which bears some of the same mutations as the South African strain, was recently found in a U.S. patient. Regeneron said it believes its antibody cocktail will remain effective against the Brazilian variant.

Read the bioRxiv study here: bit.ly/3r9T2JZ. — James Miessler