#16,179
Although there are currently two monoclonal antibody regimens (sotrovimab or the combination of casirivimab and imdevimab) that have not shown any reduction in effectiveness against any of the known COVID variants, for some time there have been concerns over Eli Lilly's combo Bamlanivimab & Etesevimab, and at the end of August the FDA had limited its EUA (Emergency Use Authorization) to:
Despite this change notification, as of September 8th (see Bamlanivimab and Etesevimab Authorized States, Territories, and U.S. Jurisdictions) this mAb combo is still available in all U.S. states and territories, since it is still believed effective against the Delta variant which comprises more than 95% of call cases right now.
But the concern is that - over time - if Delta gives way to some of the other VOIs and VOCs we've been watching, treatment using Bamlanivimab & Etesevimab could be less effective.
On Friday the CDC emailed out a COCA NOW newsletter that inadvertently left the impression that the Delta Variant might also evade this mAb treatment. At this time, there is only a cautionary note on mAbs and Delta which reads; Potential reduction in neutralization by some EUA monoclonal antibody treatments 7, 14
Overnight the CDC sent out the following email clarification.
COCA NOW Clarification COCA Memo: Monoclonal Antibodies Bamlanivimab and Etesevimab May Be Less Effective for Treating Cases of COVID-19 Caused by SARS-CoV-2 Variants
The recent COCA NOW : Monoclonal Antibodies Bamlanivimab and Etesevimab May Be Less Effective for Treating Cases of COVID-19 Caused by SARS-CoV-2 Variants COCA notification released September 10, 2021 highlighted changes made to CDC’s Variant Classification and Definitions webpage, which primarily focused on updates to Substitutions of Therapeutic Concern. These updates contained accurate information, but unintentionally indicated a possible cause for concern that this combination monoclonal antibody product was not effective against infections with the SARS-CoV-2 Delta variant.
CDC has no evidence at present that Delta variants circulating in the United States carry mutations than might confer resistance to this drug.
The information provided in the Substitutions of Concern for SARS-CoV-2 Monoclonal Antibody Therapies is based on laboratory data provided in the Fact Sheet for Health Care Providers for EUA of Bamlanivimab and Etesevimab, which indicates no change in susceptibility to bamlanivimab and etesevimab for the Delta variants. As such, clinical recommendations have not changed.
Clinicians seeking advice on the use of monoclonal antibody products authorized for emergency use in the United States for the treatment and prevention of SARS-CoV-2 should consult the NIH COVID-19 Treatment Guidelines.
Lest anything think this reduction in mAb effectiveness against some variants is a new discovery, we've been discussing it for months (see here, here, and here). The CDC's latest update (Sept 11th) to their SARS-CoV-2 Variant Classifications and Definitions webpage advises:
Treatment considerations for healthcare providers
Substitutions of Concern for SARS-CoV-2 Monoclonal Antibody Therapies
In the United States, there are three anti-SARS-CoV-2 monoclonal antibody treatments with FDA Emergency Use Authorization (EUA) for the treatment of COVID-19: bamlanivimab plus etesevimab, casirivimab plus imdevimab, and sotrovimab.
CDC’s national genomic surveillance program identifies new and emerging SARS-CoV-2 variants to determine implications for COVID-19 diagnostics, treatments, or vaccines approved or authorized for use in the United States. Sequences with similar genetic changes are grouped into lineages, and multiple lineages can have the same substitutions. For example, the E484K substitution is found in lineages B.1.351, P.1, B.1.526, and many others. Genomic surveillance efforts provide the capability to detect viruses that have reduced susceptibility to treatments more quickly.
Reduced susceptibility of SARS-CoV-2 to sotrovimab or the combination of casirivimab and imdevimab has not been reported. In laboratory studies, SARS-CoV-2 variants that contain certain substitutions in the spike protein cause a reduction in susceptibility to the combination of bamlanivimab and etesevimab*. These include the following individual or combinations of substitutions:* For some substitutions or combination of substitutions, the reduction in susceptibility is modest, and the clinical implications of this modest decrease are not known at this time. Clinicians seeking advice on the use of monoclonal antibody products authorized for emergency use in the United States for the treatment and prevention of SARS-CoV-2 should consult the NIH COVID-19 Treatment Guidelines.
- L452R
- E484K
- L452R and E484Q
- K417N, E484K, and N501Y
- K417T, E484K, and N501Y
- K417N, L452R, and T478K
- R346K, E484K, and N501Y
The data below show the national and regional unweighted proportions of SARS-CoV-2 that contain the individual or combinations of spike protein substitutions listed above. As new data become available, additional substitutions may be added below. The national and regional proportions provided below will be updated weekly.
Among the variants listed by the CDC which appear to evade the bamlanivimab and etesevimab mAb treatment are:
- VOC Beta - Significantly reduced susceptibility to the combination of bamlanivimab and etesevimab monoclonal antibody treatment,7 but other EUA monoclonal antibody treatments are available 14
- VOC Gamma - Significantly reduced susceptibility to the combination of bamlanivimab and etesevimab monoclonal antibody treatment,7 but other EUA monoclonal antibody treatments are available 14
- VOI Eta - Potential reduction in neutralization by some Emergency Use Authorization (EUA) monoclonal antibody treatments 7, 14
- VOI Iota - Reduced susceptibility to the combination of bamlanivimab and etesevimab monoclonal antibody treatment; however, the clinical implications of this are not known.7 Alternative monoclonal antibody treatments are available.14
- VOI Kappa - Potential reduction in neutralization by some EUA monoclonal antibody treatments 7, 14
Rapid evolution is a virus's best friend, and our worst enemy, during a pandemic. While it can sometimes attenuate a virus over time - so far with COVID - it has only made it more formidable.
Viruses have managed to exist for hundreds of millions of years because they are able to adapt to an ever-changing, and often hostile, environment.
An attribute our species would do well to emulate.
