April 23, 2021

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Unpublished data from a phase 3 trial of 4567 high-risk non-hospitalized people with COVID-19 show that the mAb cocktail consisting of casirivimab with imdevimab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

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.