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The US Food and Drug Administration (FDA) has granted Eli Lilly’s request to revoke emergency use authorization for the COVID-19 monoclonal antibody therapy bamlanivimab when used as a monotherapy, saying the evidence indicates that it is likely not effective against currently circulating variants.
The agency said in a letter to Lilly that bamlanivimab is still effective when used in combination with etesevimab, another Lilly anti-SARS-CoV-2 monoclonal antibody.
The FDA authorized emergency use of the combination in February. The company and the FDA are instructing infusion sites to hold on to bamlanivimab doses with an eye toward using it for combination therapy.
As of March 2, bamlanivimab was the most-distributed anti-COVID-19 monoclonal antibody, almost 800,000 doses shipped to various states and cities, according to the US Department of Health and Human Services (HHS).
“While the risk–benefit assessment for using bamlanivimab alone is no longer favorable due to the increased frequency of resistant variants, other monoclonal antibody therapies authorized for emergency use remain appropriate treatment choices when used in accordance with the authorized labeling and can help keep high risk patients with COVID-19 out of the hospital,” said Patrizia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research, in a statement. “We urge the American public to seek out these therapies when needed while we continue to use the best data available to provide patients with safe and effective treatments during this pandemic.”
The FDA’s revocation follows an April 8 recommendation by the National Institutes of Health against the use of bamlanivimab alone and against using any of the anti-SARS-CoV-2 monoclonal antibodies in hospitalized patients.
Safety Not the Issue
Neither agency has expressed concern about bamlanivimab safety. But both cite data that in the lab, vesicular stomatitis virus-based pseudovirus expressing spike protein with variant substitutions, specifically E484K and L452R, exhibit large reductions (>1000-fold) in susceptibility to bamlanivimab alone in neutralization assays.
The L452R substitution has been found in the B.1.427 and B.1.429 lineages, both first detected in California, and now accounting for more than 20% of cases in eight states, and more than 10% in an additional two states, according to genomic surveillance conducted by the US Centers for Disease Control and Prevention, said the FDA.
The agency also noted recent reports that variants with the E484K mutation are circulating at rates exceeding 10% in the New York City metropolitan area, including northern New Jersey.
Bamlanivimab was first granted emergency use authorization in November as a monotherapy for treatment of mild to moderate COVID-19 in adults and pediatric patients at high risk for progressing to severe COVID-19 and/or hospitalization.
The agency urges clinicians to consider using alternatives, including Regeneron’s combo (casirivimab and imdevimab, administered together), and bamlanivimab and etesevimab given together, for the same uses as previously authorized for bamlanivimab alone.
Only 148,000 doses of casirivimab/imdevimab had been distributed as of February 2, according to the latest data available from HHS.
Alicia Ault is a Lutherville, Maryland-based freelance journalist whose work has appeared in publications including Smithsonian.com, the New York Times, and the Washington Post. You can find her on Twitter @aliciaault.