Coronavirus Variants and their Impact on Treatment

New coronavirus variants are circulating in the United States. The Department of Health and Human Services (HHS) established a SARS-CoV-2 interagency group (SIG) to improve coordination among government agencies in characterizing and monitoring new variants and determining their potential impact on COVID-19 treatment and prevention measures. The SIG includes the Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), US Food and Drug Administration (FDA), Biomedical Advanced Research and Development Authority (BARDA), and Department of Defense (DoD).

They established a classification scheme to describe new strains of the virus as variants of interest, concern, or of high consequence. Three variants of interest, two that were first identified in New York (B.1.526, B.1.525) and one first identified in Brazil (P.2), share a common mutation at D614G and may spread more quickly than viruses without this mutation.1

The CDC is closely monitoring several variants of concern that were first identified in the United Kingdom (B.1.1.7), South Africa (B.1.351), Brazil (P.1), and two variants first identified in California (B.1.427, B.142). These variants may have an impact on diagnostic testing and the efficacy of treatments or vaccines and are associated with increased transmissibility and disease severity compared with earlier coronavirus variants. Currently, no variants of high consequence have been identified.1

Monoclonal antibodies that have received Emergency Use Authorization (EUA) by the FDA—bamlanivimab, bamlanivimab plus etesevimab, and casirivimab plus imdevimab—have shown efficacy in preventing mild-to-moderate COVID-19 from progressing to severe disease in people with certain risk factors.2–7 These treatments are effective against the variant that emerged from the United Kingdom. However, because of concern that bamlanivimab monotherapy is ineffective against the California variants, its distribution in California, Arizona, and Nevada was halted.8 Preclinical data of bamlanivimab with etesevimab show that this combination continues to remain effective against the California variants. This antibody cocktail in addition to the casirivimab and imdevimab combination continue to be available in all states based on their respective EUAs.8

*Since the time of this writing, distribution of bamlanivimab as monotherapy has been halted in all U.S. states.

References
 

  1. Centers for Disease Control and Prevention (CDC). SARS-CoV-2 variant classifications and definitions. (www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance/variant-info.html#Concern) Accessed 3/23/2021.
  2. Bamlanivimab Emergency Use Authorization fact sheet, revised 3/2021. (www.fda.gov/media/143603/download) Accessed 3/24/2021.
  3. 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.
  4. Bamlanivimab and etesevimab Emergency Use Authorization fact sheet, revised 3/2021. (www.fda.gov/media/145802/download) Accessed 3/34/2021
  5. 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.
  6. Casirivimab and imdevimab Emergency Use Authorization fact sheet, revised 3/2021. (www.regeneron.com/sites/default/files/treatment-covid19-eua-fact-sheet-for-hcp.pdf) Accessed 3/24/2021.
  7. 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.
  8. BioSpace. HHS halts bamlanivimab distribution in three states as COVID-19 variants spread. (www.biospace.com/article/hhs-suspends-use-of-monoclonal-antibody-cocktail-in-three-states-due-to-rise-of-california-covid-19-variant/?keywords=bamlanivimab) Accessed 3/23/2021.
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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.

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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