bamlanivimab and etesevimab together

This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.

Will bamlanivimab and etesevimab together be effective in the treatment of COVID-19 infections caused by circulating SARS-CoV-2 variants?

Lilly developed bamlanivimab and etesevimab for administration together to be prepared for the spread of SARS-CoV-2 variants that could resist treatment with either monoclonal antibody alone.

US_cFAQ_BAM_ETE105_CIRCULATING_VARIANTS_EFFICACY_COVID-19
US_cFAQ_BAM_ETE105_CIRCULATING_VARIANTS_EFFICACY_COVID-19
en-US

Bamlanivimab and Etesevimab Emergency Use Authorization

Bamlanivimab and etesevimab have not been approved, but have only been authorized for emergency use by FDA to be administered together 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.1,2

Bamlanivimab and etesevimab are authorized to be administered together 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 only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of the bamlanivimab and etesevimab under Section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.1,2

For information on the authorized use of bamlanivimab and etesevimab together and mandatory requirements under the EUA, please review the FDA Letter of Authorization, Fact Sheet for Healthcare Providers, and Fact Sheet for Patients/Caregivers at BAMandETE.com.

Emerging SARS-CoV-2 Variants and Prevalence

Multiple variants of SARS-CoV-2 have been identified and are circulating globally. The following variants of concern are currently in the US:

  • The UK identified a variant called B.1.1.7 with a large number of mutations in the fall of 2020. This variant has been shown to spread more easily and quickly than other variants. It has since been detected in many countries around the world. This variant was first detected in the US at the end of December 2020.
  • In South Africa, a variant called B.1.351 emerged. Originally detected in early October 2020, B.1.351 shares some mutations with B.1.1.7. Cases caused by this variant have been reported in the US at the end of January 2021.
  • In Brazil, a variant called P.1 emerged. This variant contains a set of additional mutations that may affect its ability to be recognized by antibodies. This variant was first detected in the US at the end of January 2021.
  • The US has identified the
    • California variant, L452R, found in B.1.429/B.1.427 lineages (a.k.a. 20C/CAL.20C), and
    • New York variant, found in the B.1.526 in 2021.2-5

According to real-time data accessed via the GISAID COVID-19 variant tracker (https://www.gisaid.org), these variants currently represent over half of COVID-19 infections presently in the US.3,6

Furthermore, prevalence of these variants or mutations can differ by country or even by state.4,5

 

Bamlanivimab and Etesevimab Fact Sheet for Healthcare Providers

Circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies. Health care providers should review the Antiviral Resistance information in Section 15 of the Fact Sheet for details regarding specific variants and resistance, and refer to the CDC website (https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-proportions.html) as well as information from state and local health authorities regarding reports of viral variants of importance in their region to guide treatment decisions.2

Antiviral Resistance

There is a potential risk of treatment failure due to the development of viral variants that are resistant to bamlanivimab and/or etesevimab. Prescribing healthcare providers should consider the prevalence of SARS-CoV-2 variants in their area, where data are available, when considering treatment options.2

Global Variants Surveillance

Evaluation of susceptibility of variants identified through global surveillance in subjects treated with bamlanivimab and etesevimab is ongoing.2

Nonclinical Results

Pseudotyped VLP evaluation of amino acid substitutions identified in global surveillance showed that the

  • V483A substitution reduced susceptibility to bamlanivimab 48-fold, but activity was maintained with etesevimab, and with bamlanivimab and etesevimab together, and
  • N501Y and N501T substitutions reduced susceptibility to etesevimab approximately 5-fold and 20-fold, respectively, but activity was maintained with bamlanivimab alone, and with bamlanivimab and etesevimab together.7

Bamlanivimab alone and bamlanivimab and etesevimab together retained activity against a SARS-CoV-2 B.1.1.7 lineage (UK origin) virus and related pseudotyped VLPs expressing del69-70 + N501Y found in the B.1.1.7 variant (UK origin) (see Pseudotyped Virus-Like Particle Neutralization Data for SARS-CoV-2 Variant Substitutions with Bamlanivimab and Etesevimab Together (1:2 Molar Ratio) and  Authentic Live SARS-CoV-2 Neutralization Data for Bamlanivimab and Etesevimab Together (1:2 Molar Ratio)).2

Pseudotyped VLPs expressing spike protein from the B.1.351 lineage (South Africa origin) or substitutions K417N + E484K + N501Y found in this lineage had reduced susceptibility to bamlanivimab and etesevimab together of 215-fold or >45-fold, respectively (see Pseudotyped Virus-Like Particle Neutralization Data for SARS-CoV-2 Variant Substitutions with Bamlanivimab and Etesevimab Together (1:2 Molar Ratio)).2

Pseudotyped VLPs expressing spike protein from the P.1 lineage (Brazil origin) or K417T + E484K + N501Y found in the P.1 lineage had reduced susceptibility to bamlanivimab and etesevimab together of >46-fold or >511-fold, respectively (see Pseudotyped Virus-Like Particle Neutralization Data for SARS-CoV-2 Variant Substitutions with Bamlanivimab and Etesevimab Together (1:2 Molar Ratio).2

Pseudotyped VLPs expressing spike protein from the B.1.427/B.1.429 lineages (California origin)  or the L452R substitution found in this lineage, maintained activity for etesevimab but showed reduced susceptibility to bamlanivimab and etesevimab together of 9-fold or 15-fold, respectively (see Pseudotyped Virus-Like Particle Neutralization Data for SARS-CoV-2 Variant Substitutions with Bamlanivimab and Etesevimab Together (1:2 Molar Ratio)).2

Pseudotyped Virus-Like Particle Neutralization Data for SARS-CoV-2 Variant Substitutions with Bamlanivimab and Etesevimab Together (1:2 Molar Ratio)2

Lineage with Spike Protein Substitution

Key Substitutions Testeda

Fold Reduction in Susceptibility

B.1.1.7 (UK origin)

N501Y

no changeb

B.1.351 (South Africa origin)

K417N + E484K + N501Y

>215c

P.1 (Brazil origin)

K417T + E484K + N501Y

>46c

B.1.427/B.1.429 (California origin)

L452R

9d

B.1.526 (New York origin)e

E484K

31

Abbreviations: SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; UK = United Kingdom.

aSpike variants reflective of the consensus sequences for the lineage were tested when available; for variants with more than one substitution of concern, only the one(s) with the greatest impact on activity is(are) listed.

bNo change: <5-fold reduction in susceptibility.

cBamlanivimab and etesevimab together are unlikely to be active against variants from this lineage. No activity observed at the highest concentration tested.

dEtesevimab retains activity against this variant.

eIsolates of the B.1.526 lineage harbor several spike protein amino acid substitutions, and not all isolates contain the E484K substitution (as of February 2021). This assay was conducted using pseudotyped VLPs with the E484K substitution only.

 Authentica Live SARS-CoV-2 Neutralization Data for Bamlanivimab and Etesevimab Together (1:2 Molar Ratio)2

Lineage with Spike Protein Substitution

Key Substitutions Testedb

Fold Reduction in Susceptibility

B.1.1.7 (UK origin)

N501Y

no changec

B.1.526 (New York origin)d

E484K

10.5

Abbreviations: UK = United Kingdom

aThe B.1.1.7 variant was assessed using cell culture-expanded virus; the B.1.526/E484K substitution was assessed using recombinant SARS-CoV-2 (USA/WA/1/2020 isolate).

bFor variants with more than one substitution of concer, only the one(s) with the greatest impact on activity is (are) listed.

cNo change: <5-fold reduction in susceptibility

dNot all isolates of the New York lineage harbor the E484K substitution (as of February 2021).

Due to the lack of pseudotyped VLP neutralization activity of both bamlanivimab and etesevimab against the substitutions in B.1.351 (South Africa origin) and P.1 (Brazil origin), it is unlikely that bamlanivimab and etesevimab together will be active against these variants.2

Clinical Results

It is unclear how small reductions in susceptibility to bamlanivimab and etesevimab seen in authentic or recombinant SARS-CoV-2 or pseudotyped VLP assays correlate with clinical outcomes.2

B.1.526 lineage (New York origin)

SARS-CoV-2 (USA/WA/1/2020 isolate) engineered to express the E484K substitution present in the B.1.526 lineage (New York origin) retained activity to etesevimab alone but showed reduced susceptibility to bamlanivimab and etesevimab together of 10-fold (see  Authentic Live SARS-CoV-2 Neutralization Data for Bamlanivimab and Etesevimab Together (1:2 Molar Ratio)).2

Available nonclinical and clinical PK data indicate that etesevimab at the authorized dose may retain activity against the B.1.526 variant clinically, although only very limited data are currently available from patients infected with this variant in clinical trials.2

L452R variant (California origin)

Preliminary clinical evidence indicates that the administration of bamlanivimab and etesevimab together result in similar viral load reductions in participants infected with the L452R variant (California origin) as observed in those who were infected with bamlanivimab-sensitive strains.2

Of the 134 participants infected with the L452R variant at baseline in the Phase 3 portion of BLAZE-1, 3 of the 50 individuals treated with placebo (6%) and 1 of the 84 participants treated with bamlanivimab 700 mg and etesevimab 1400 mg (1%) were hospitalized (p=.15).2

References

The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).

1United States Food and Drug Administration. Bamlanivimab and Etesevimab FDA Emergency Use Authorization Letter. Issued February 9, 2021. Accessed February 9, 2021. http://pi.lilly.com/eua/bam-and-ete-eua-fda-authorization-letter.pdf

2Fact sheet for healthcare providers. Emergency Use Authorization (EUA) of bamlanivimab and etesevimab. US Food and Drug Administration (FDA). 2021.

3Centers for Disease Control and Prevention. About variants of the virus that causes COVID-19. Updated April 2, 2021. Accessed April 22, 2021. https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant.html

4GISAID. Tracking of hcov19 Variants. Accessed March 12, 2021. https://www.gisaid.org/hcov19-variants/

5Data on file, Eli Lilly and Company and/or one of its subsidiaries.

6GISAID. Tracking of hcov19 Variants. Accessed April 22, 2021. https://www.gisaid.org/hcov19-variants/

7U. S. Food and Drug Administration (FDA). Fact Sheet for Health Care Providers. Emergency Use Authorization (EUA) of bamlanivimab. 2021.

Glossary

CDC = Centers for Disease Control and Prevention

COVID-19 = coronavirus disease 2019

EUA = emergency use authorization

FDA = Food and Drug Administration

SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2

UK = United Kingdom

US = United States

VLP = virus-like particles

Date of Last Review: May 14, 2021


Contact Lilly

Call Us

If you have immediate questions regarding COVID-19, or to report an Adverse Event or Product Complaint, please call us.

Daily Live Support: 9am to 7pm ET.
After Hours: Call Back Support Available

Or you can

Chat with us

Chat with us

Submit a Request

Visit Us @LillyMedical