FDA Revokes Lilly’s bamlanivimab EUA As Its Efficacy Wanes Against SARS-CoV-2 Variants

FDA Revokes Lilly’s bamlanivimab EUA As Its Efficacy Wanes Against SARS-CoV-2 Variants

The U.S. Food and Drug Administration (FDA) just recently revoked the emergency use authorization (EUA) for bamlanivimab, the investigational monoclonal therapy, when administered alone for the use of treatment for mild-to-moderate COVID-19 in adults and certain pediatric patients. The FDA has determined that the known and potential benefits of the investigational monoclonal antibody when administered alone no longer outweigh the known and possible risks for its authorized use. Why? Because of an ongoing analysis by the FDA, when combined with emerging data, indicate that sustained increase of SARS-CoV-2 viral variants that are resistant to the monoclonal antibody product produced by Eli Lilly and Co. (Lilly) result in increased risk for treatment failure. Consequently, the FDA has revoked the EUA. Bamlanivimab also faltered in the NIH-sponsored ACTIV- 3 trial centering on hospitalized patients last October. The monoclonal antibody can still be used with Lilly’s etesevimab, licensed by a Chinese biotech, based on data generated from the BLAZE-1 clinical trial. Also still available is the monoclonal antibody cocktail produced by Regeneron known as REGEN-COV (Casirivimab and imdevimab).

The Situation

On Nov. 9, 2020, based on the totality of scientific evidence available at the time, the FDA issued an EUA to Lilly authorizing the emergency use of bamlanivimab alone for the treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progressing to severe COVID-19 and/or hospitalization. Importantly, although the FDA is now revoking this EUA, alternative monoclonal antibody therapies remain available under EUA, including REGEN-COV (casirivimab and imdevimab, administered together), and bamlanivimab and etesevimab, administered together, for the same uses as previously authorized for bamlanivimab alone. The FDA believes that these alternative monoclonal antibody therapies remain appropriate to treat patients with COVID-19 when used in accordance with the authorized labeling based on information available at this time.

Recently, the Director of the FDA’s Center for Drug Evaluation and Research Patrizia Cavazzoni, MD, declared:

“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. 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.”

What are Monoclonal Antibodies?

Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off harmful pathogens such as viruses, like SARS-CoV-2. Like other infectious organisms, SARS-CoV-2 can mutate over time, resulting in genetic variation in the population of circulating viral strains.

FDA Responsibility: The Safety of the Public

The FDA has a responsibility to regularly review the appropriateness of an EUA, and as such, the agency will review emerging information associated with the emergency uses for the authorized products. Recent data from the U.S. Centers for Disease Control and Prevention’s (CDC) national genomic surveillance program show an increased frequency of SARS-CoV-2 variants that are expected to be resistant to bamlanivimab administered alone. As of mid-March 2021, approximately 20% of viruses sequenced in the U.S. were reported as variants expected to be resistant to bamlanivimab alone, increasing from approximately 5% in mid-January 2021.

Additionally, there are currently no testing technologies available that enable health care providers to test individual patients for SARS-CoV-2 viral variants prior to start of treatment with monoclonal antibodies. Therefore, empiric treatment with monoclonal antibody therapies that are expected to work broadly against all variants across the nation should be used to reduce the likelihood of treatment failure.

The FDA will continue working closely with other federal governmental agencies, including the CDC and the National Institutes of Health, on the surveillance of variants that may impact the monoclonal antibody therapies authorized for emergency use. The agency remains committed to providing timely and transparent communication as additional information becomes available.

What is etesevimab?

Etesevimab (LY-CoV016, also known as JS016) is a recombinant fully human monoclonal neutralizing antibody, which specifically binds to the SARS-CoV-2 surface spike protein receptor binding domain with high affinity and can block the binding of the virus to the ACE2 host cell surface receptor. Point mutations were introduced into the native human IgG1 antibody to mitigate effector function. Lilly licensed etesevimab from Junshi Biosciences after it was jointly developed by Junshi Biosciences and the Institute of Microbiology, Chinese Academy of Science (IMCAS). Junshi Biosciences leads development in Greater China, while Lilly leads development in the rest of the world.

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Responses

  1. It seems the change is only to demand that bam-la-ni-vi-mab always be administered TOGETHER with ete-se-vi-mab, another Eli Lilly variant. Due to virus mutation they strive for a broader effect buy combining the two monochlonal antibody variants. So a new EUA has been issued to cover that combination. Seems this is among the more interesting ‘early treatment’ medicines for people in risk of severe illness if left untreated.