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Unpublished data from a phase 3 trial of 4567 high-risk non-hospitalized people with COVID-19 show that the mAb cocktail consisting of casirivimab with imdevimab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.
Menu

Patient Toolkit

The COVID FRONTLINE Patient Toolkit is a resource center for patients who have been diagnosed with or who are interested in learning about COVID-19. Choose from the options below to learn more.

This activity is provided by Med Learning Group. This activity is co-provided by Ultimate Medical Academy/CCM.
This activity is supported by educational grants from AbbVie, Astellas, Genentech, Lilly, Merck & Co., Inc., Pfizer and Regeneron Pharmaceuticals, Inc.

Copyright © 2019 | COVID Frontline | All Rights Reserved | Website by Divigner

Updates in the Treatment and Prevention of COVID-19​

Subcutaneous Administration of Casirivimab and Imdevimab Reduced the Risk of Symptomatic COVID-19 by 81% Among Household Contacts

Top-line results from a phase 3 trial showed that the combination of casirivimab and imdevimab reduced the risk of symptomatic infections by 81% among household contacts of SARS-CoV-2 infected individuals. The trial enrolled 1,505 individuals who did not have COVID-19 symptoms or anti-SARS-CoV-2 antibodies, but who lived in the same household as an individual who tested positive for SARS-CoV-2 within the prior 4 days. A single subcutaneous injection of casirivimab and imdevimab provided rapid protection to those with exposure to SARS-CoV-2 at home, with protection against symptomatic infections ranging from 72% in the first week to 93% in subsequent weeks. Individuals who developed symptomatic infections despite casirivimab and imdevimab therapy had a shorter duration of symptoms compared with those who received placebo (1 week vs 3 weeks, respectively). Infected individuals who received therapy also cleared the virus faster. Adverse events (AEs) occurred in 20% of patients receiving casirivimab and imdevimab and 29% of patients receiving placebo. Injection site reactions, all of which were grades 1-2, occurred in 4% of patients in the treatment group and 2% of placebo participants.

Casirivimab and Imdevimab Significantly Reduced Progression to Symptomatic COVID-19 in Recently Infected Asymptomatic Patients

In a phase 3 trial of 204 recently infected asymptomatic COVID-19 patients, subcutaneous administration of casirivimab and imdevimab reduced the overall risk of progressing to symptomatic COVID-19 by 31%, and by 76% after the third day. In addition to reducing the risk of symptomatic infections, the top-line results report that the combination of casirivimab and imdevimab shortened the total number of weeks patients experienced symptoms by 45% and reduced the viral burden by more than 90%. No patients withdrew from the trial due to AEs in either group. Casirivimab and imdevimab are investigational drugs with emergency use authorization for the treatment of individuals with mild-to-moderate COVID-19 who are at high-risk of progressing to severe COVID-19 or hospitalization. Casirivimab and imdevimab (REGEN-COV™) continues to be evaluated in clinical trials in multiple settings for COVID-19, including the open-label RECOVERY trial of hospitalized patients in the UK.

Johnson & Johnson COVID-19 Vaccine Administration Paused

The Centers for Disease Control and Prevention (CDC) and the Federal Drug Administration (FDA) are recommending a pause in the use of the Ad26.COV2.S vaccine developed by Johnson & Johnson (Janssen) as they review data involving 6 reported cases of a rare and severe type of blood clot in individuals after vaccination. The vaccine has been administered to more than 6.8 million individuals in the US. In all 6 reported cases, a type of blood clot called cerebral venous sinus thrombosis (CVST) occurred in combination with low platelet levels (thrombocytopenia). Treatment of CVST differs from other blood clots and administration of heparin may be dangerous in these patients. All 6 cases occurred among women aged 18 to 48 years and symptoms usually occurred 6 to 13 days after vaccination. People who develop severe headache, abdominal pain, leg pain, or shortness of breath within 3 weeks after vaccination should contact their healthcare provider.

References:

Regeneron Press Release. Phase 3 Prevention Trial Showed 81% Reduced Risk of Symptomatic SARS-CoV-2 Infections with Subcutaneous Administration of REGEN-COV™ (Casirivimab and Imdevimab). April 12, 2021. Available at: https://investor.regeneron.com/news-releases/news-release-details/phase-3-prevention-trial-showed-81-reduced-risk-symptomatic-sars

Regeneron Press Release. Phase 3 Treatment Trial in Recently Infected Asymptomatic Patients Showed REGEN-COV™ (Casirivimab and Imdevimab) Significantly Reduced Progression to Symptomatic COVID-19. April 12, 2021. Available at: https://investor.regeneron.com/news-releases/news-release-details/phase-3-treatment-trial-recently-infected-asymptomatic-patients

FDA Statement. Joint CDC and FDA Statement on Johnson & Johnson COVID-19 Vaccine. April 13, 2021. Available at: https://www.fda.gov/news-events/press-announcements/joint-cdc-and-fda-statement-johnson-johnson-covid-19-vaccine