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COVID-19 Monoclonal Antibodies and Effectiveness Against Variants

The Centers for Disease Control and Prevention (CDC) report that the COVID-19 variant first identified in the U.K.—B.1.1.7—is the most common cause of new infection in the U.S, particularly in Florida, Michigan, Minnesota, Massachusetts, Colorado, California, Maryland, Pennsylvania, and New Jersey.1 This strain has evidence of being more infectious and causing more severe disease compared with the original strain.2 Other variants of concern circulating in the U.S. are P.1 and B.1.351, first identified in Brazil and South Africa, respectively, and B.1.427 and B.1.429 which were first identified in California.3

Monoclonal antibodies (mAbs) and mAb cocktails that have received Emergency Use Authorization (EUA) by the US Food and Drug Administration (FDA) have shown efficacy in preventing mild-to- moderate COVID-19 from progressing to severe disease in people with certain risk factors.4–6 Because of concern that single-agent mAbs are ineffective against the variants, the distribution of bamlanivimab (LY-CoV555) as monotherapy was halted nationwide.7

Preclinical data of bamlanivimab with etesevimab (LY-CoV016/JS016) show that this combination continues to remain effective against the B.1.1.7 variant but has reduced activity against the B.1.351 variant; it continues to be available based on its EUA.8,9

Unpublished data from a phase 3 trial of 4567 high-risk non-hospitalized people with COVID-19 show that the mAb cocktail consisting of casirivimab with imdevimab (REGN-COV™) reduced hospitalizations or death by 70% and significantly reduced symptom duration by 4 days compared with placebo. All doses of the antibody cocktail—8000 mg, 2400 mg, and 1200 mg—showed similar efficacy.10 A companion dose-ranging phase 2 trial of 803 non-hospitalized people with COVID-19 showed significant and comparable viral reductions for all REGEN-COV doses tested, including as low as 300 mg.10 The FDA recently updated U.S. EUA fact sheets for all authorized monoclonal antibody treatments, indicating that compared with other mAbs, REGEN-COV retains potency against several key variants of concern circulating in the U.S.8,11

REGEN-COV continues to be investigated on ongoing clinical trials in both the outpatient and hospital settings.

References

  1. Centers for Disease Control and Prevention (CDC). US COVID-19 cases caused by variants. Updated 4/6/2021. (www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html) Accessed 4/8/2021.
  2. Davies NG, Abbott S, Barnard RC, et al. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science. 2021;March 3: Epub ahead of print.
  3. CDC. SARS-CoV-2 Variant classifications and definitions. Updated 3/16/2021. (www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance/variant-info.html#Concern) Accessed 4/8/2021.
  4. Weinreich DM, Sivapalasingam S, Norton T, et al. REGN-COV2, a neutralizing antibody cocktail in outpatients with COVID-19. N Engl J Med. 2021;384:238-251.
  5. Chen P, Nirula A, Heller B, et al. SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with Covid-19. N Engl J Med. 2021;384:229-237.
  6. Gottlieb RL, Nirula A, Chen P, et al. Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: a randomized clinical trial. JAMA. 2021;325:632-644.
  7. Department of Health and Human Services (DHHS). Outpatient monoclonal antibody treatment for COVID-19 made available under emergency use authorization. (www.phe.gov/emergency/events/COVID19/investigationMCM/Bamlanivimab/Pages/default.aspx) Accessed 4/8/2021.
  8. US Food and Drug Administration (FDA). Fact sheet for health care providers: Emergency Use Authorization (EUA) of bamlanivimab and etesevimab. Updated 3/2021. (www.fda.gov/media/145802/download). Accessed 4/8/2021.
  9. Wang P, Nair JS, Liu L, et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature. 2021;Mar 8: Epub ahead of print.
  10. Regeneron press release. Phase 3 trial shows REGEN-COV™ (casirivimab with imdevimab) antibody cocktail reduced hospitalization or death by 70% in non-hospitalized COVID-19 patients. (https://investor.regeneron.com/node/24986/pdf) Accessed 4/8/2021.
  11. FDA. Fact sheet for health care providers Emergency Use Authorization (EUA) of REGEN-COV (casirivimab with imdevimab). Updated 3/2021. (www.fda.gov/media/145611/download) Accessed 4/8/2021.

This activity is co-provided by Ultimate Medical Academy/Complete Conference Management (CCM).
This activity is supported by educational grants from AbbVie, Astellas, Genentech, Lilly, Merck & Co., Inc., Pfizer and Regeneron Pharmaceuticals, Inc.

Copyright © 2019 Med Learning Group. Built by Divigner. All Rights Reserved.
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Updates in the Treatment and Prevention of COVID-19​

Bebtelovimab Is the Only Monoclonal Antibody That Retains Activity Against Omicron Subvariants

The Omicron subvariants BA.2 and BA.2.12.1 now account for 99% of all COVID-19 cases in the United States. Studies assessing the neutralizing activity of monoclonal antibodies for the treatment of COVID-19 have found that only bebtelovimab retains activity against BA.2 and BA.2.12.1. Other monoclonal antibodies, including sotrovimab, bamlanivimab, etesevimab, casirivimab, and imdevimab, are not effective against these new subvariants and are not currently authorized by the US Food and Drug Administration (FDA) to treat COVID-19 due to the high incidence of Omicron BA.2.

Bebtelovimab is authorized for emergency use by the FDA for the treatment of mild-to-moderate COVID-19 in patients 12 years and older weighing at least 40 kg with positive results of direct SARS-CoV-2 viral testing who are at high risk for progression to severe COVID-19, including hospitalization or death. Bebtelovimab should be administered as soon as possible after positive SARS-CoV-2 results and within 7 days of symptom onset.

FDA Approves Baricitinib for Hospitalized COVID-19 Patients

Baricitinib, an oral Janus kinase (JAK) inhibitor, is now FDA-approved for the treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). It is also authorized for emergency use by the FDA for hospitalized pediatric patients between 2 and 18 years of age who require oxygen support. The approval of baricitinib is based on efficacy and safety data from the ACTT-2 and COV-BARRIER clinical trials. In ACTT-2, baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time, particularly in patients receiving high-flow oxygen or noninvasive ventilation (10 days vs 18 days; rate ratio for recovery, 1.51; 95% confidence interval (CI), 1.10 to 2.08). The 28-day mortality was 5.1% with baricitinib plus remdesivir and 7.8% with remdesivir alone (hazard ratio [HR] for death, 0.65; 95% CI, 0.39 to 1.09). The COV-BARRIER trial found that baricitinib, in addition to standard of care (SoC), was associated with reduced 28-day mortality in hospitalized adults with COVID-19 compared with SoC alone (8% vs 13%; HR, 0.57; 95% CI, 0.41 to 0.78; P= .0018). The 60-day all-cause mortality was 10% with baricitinib plus SoC versus 15% with SoC (P= .005).

References:
Baricitinib fact sheet for healthcare providers. May 2022. (https://www.fda.gov/media/143823/download).  Accessed 5.24.2022.

Baricitinib (Olumiant®) PI 2022 (https://pi.lilly.com/us/olumiant-uspi.pdf). Accessed 5.24.2022.

Bebtelovimab fact sheet for healthcare providers. May 2022. (https://www.fda.gov/media/156152/download).  Accessed 5.24.2022.

Centers for Disease Control and Prevention (CDC). COVID data tracker. May 23, 2022. (https://covid.cdc.gov/covid-data-tracker/#variant-proportions). Accessed 5.24.2022.

Iketani S, et al. Antibody evasion properties of SARS-CoV-2 Omicron sublineages. Nature. 2022;604:553-556.

Kalil AC, et al. Baricitinib plus remdesivir for hospitalized adults with COVID-19. N Engl J Med. 2021;384:795-807.

Marconi VC, et al. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Resp Med. 2021;9:1407-1418.