monoclonal antibody to spike glycoprotein of SARS-CoV2 (COVID-19)
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Introduction
bamlanivimab/etesevimab, casirivimab/imdevimab, & sotrovimab
Indications
* not effective against Omicron varients[17]
Contraindications
- not authorized hospitalized patients or patients who require oxygen therapy for COVID-19
* may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation
Dosage
- Bamlanivimab (700 mg) plus etesevimab (1400 mg) once by IV infusion
- Casirivimab (1200 mg) plus imdevimab (1200 mg) once by IV infusion[8]
Clinical significance
- monoclonal antibodies to spike glycoprotein
- not useful for hospitalized patients with COVID-19 or if hypoxic[2]
- casirivimab in combination with imdevimab (casirivimab/imdevimab) (REGEN-COV)
- both monoclonal antibodies directed against the spike protein
- received emergency use authorization from the FDA for treatment of outpatients with COVID-19 >= 14 years of age >= 40 kg, especially adults >= 65 years at risk for severe disease
- most effective in COVID-19 patients who haven't yet elicited an immune response or in those with a high viral load[3]
- proposed for prevention of COVID-19 in people with high-risk exposures[3]
- appears to be effective against B.1.351 (Beta) variant from South Africa, P.1 (Gamma) variant from Brazil[9][11] & B.1.617.2 (Delta) variant from India[12]
- ineffective against Omicron variant, off market Jan 2022
- monoclonal antibody bamlanivimab (LY-CoV555) directed against spike glycoprotein
- emergency use authorization for outpatients > 65 years with chronic disease[2]
- bamlanivimab in combination with etesevimab reduces viral load at day 11[4]
- bamlanivimab monotherapy does not reduce viral load[4]
- bamlanivimab + etesevimab not effective against B.1.351 (Beta) or P.1 (Gamma) variants[9][11] or Omicron variant[16]
- monoclonal antibody sotrovimab directed against spike glycoprotein
- emergency use authorization for outpatients (GlaxoSmithKline)
- activity against SARS-CoV2 variants, including those from the U.K., South Africa, Brazil, California, New York, & India
- S309 human monoclonal SARS CoV antibody cross neutralizes SARS CoV-2 via binding to the receptor(ACE2)-binding domain of the spike glyoprotein[5]
- S309 may be useful for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease[5]
- VIR-7831 (Vir & Glaxo) reduces hospitalization & death by 85%[7]
- NIH COVID-19 Treatment Guidelines Panel says not enough evidence to recommend for or against use of casirivimab plus imdevimab for COVID-19[6]
- variants less susceptible to monoclonal antibodies in vitro, esp bamlanivimab[8]
Mechanism of action
- monoclonal antibody specifically directed against the spike protein of SARS-CoV2
Notes
- ultrapotent antibodies from convalescent serum effective with high titers across all 23 SARS-CoV2 variants, including alpha, beta, delta & presumably gamma[14]
- spike glycoprotein binding site has been determined
- customized monoclonal antibodies & mRNA vaccines presumably to follow
- 54042-4 is a potently neutralizing SARS-CoV2 antibody[15]
- the epitope of 54042-4 is highly conserved among current SARS-CoV2 isolates
- 54042-4 maintains potent neutralization against Alpha, Beta, Gamma, & Delta variants
- not effective against Omicron variants[17]
- the epitope of 54042-4 is highly conserved among current SARS-CoV2 isolates
More general terms
More specific terms
- 'bebtelovimab
- bamlanivimab (LY-CoV555)
- casirivimab
- cilgavimab
- cilgavimab/tixagevimab (Evusheld, AZD7442)
- etesevimab
- imdevimab
- pemivibart (Pemgarda)
- S309 monoclonal antibody
- sotrovimab
- tixagevimab
- VIR-7831
References
- ↑ FDA News Release. Nov 21, 2020 Coronavirus (COVID-19) Update: FDA Authorizes Monoclonal Antibodies for Treatment of COVID-19 https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibodies-treatment-covid-19
- ↑ 2.0 2.1 2.2 Chen P, Nirula A, Heller B et al SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. N Engl J Med 2020. Oct 28 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33113295 https://www.nejm.org/doi/full/10.1056/NEJMoa2029849
FDA News Release. Nov 9, 2020 Coronavirus (COVID-19) Update: FDA Authorizes Monoclonal Antibody for Treatment of COVID-19. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibody-treatment-covid-19
NIH COVID-19 Treatment Guidelines. Nov 18, 2020. The COVID-19 Treatment Guidelines Panel's Statement on the Emergency Use Authorization of Bamlanivimab for the Treatment of COVID-19. https://www.covid19treatmentguidelines.nih.gov/statement-on-bamlanivimab-eua/
ACTIV-3/TICO LY-CoV555 Study Group A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19. N Engl J Med 2020. Dec 22. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33356051 https://www.nejm.org/doi/full/10.1056/NEJMoa2033130 - ↑ 3.0 3.1 3.2 Weinreich DM, Sivapalasingam S, Norton T et al REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. N Engl J Med 2020. Dec 17 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33332778 https://www.nejm.org/doi/full/10.1056/NEJMoa2035002
Regeneron Pharmaceuticals. Jan 26, 2021 Regeneron Reports Positive Interim Data with REGEN-COV<TM> Antibody Cocktail used as Passive Vaccine to Prevent COVID-19. https://www.prnewswire.com/news-releases/regeneron-reports-positive-interim-data-with-regen-cov-antibody-cocktail-used-as-passive-vaccine-to-prevent-covid-19-301214619.html - ↑ 4.0 4.1 4.2 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-19A Randomized Clinical Trial. JAMA. Published online January 21, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33475701 https://jamanetwork.com/journals/jama/fullarticle/2775647
Malani PN, Golub RM. Neutralizing Monoclonal Antibody for Mild to Moderate COVID-19. JAMA. Published online January 21, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33475716 https://jamanetwork.com/journals/jama/fullarticle/2775645
Lily Investors. News Release. March 10, 2021 Lilly's bamlanivimab and etesevimab together reduced hospitalizations and death in Phase 3 trial for early COVID-19. https://investor.lilly.com/news-releases/news-release-details/lillys-bamlanivimab-and-etesevimab-together-reduced - ↑ 5.0 5.1 5.2 Pinto D, Park YJ, Beltramello M et al Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature. May 18, 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32422645 https://www.nature.com/articles/s41586-020-2349-y
- ↑ 6.0 6.1 FDA News Release. Nov 21, 2020 Coronavirus (COVID-19) Update: FDA Authorizes Monoclonal Antibodies for Treatment of COVID-19 https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibodies-treatment-covid-19
NIH COVID-19 Treatment Guidelimes. Dec 2, 2020 The COVID-19 Treatment Guidelines Panel's Statement on the Emergency Use Authorization of the Casirivimab Plus Imdevimab Combination for the Treatment of COVID-19. https://www.covid19treatmentguidelines.nih.gov/statement-on-casirivimab-plus-imdevimab-eua/ - ↑ 7.0 7.1 7.2 Walker J Covid-19 Antibody Drug Effective in Study,GlaxoSmithKline and Vir Say Wall Street Journal. March 10, 2021 https://www.wsj.com/articles/covid-19-antibody-drug-effective-in-study-glaxosmithkline-and-vir-say-11615433671
- ↑ 8.0 8.1 8.2 National Institutes of Health (NIH) The COVID-19 Treatment Guidelines Panel's Statement on the Emergency Use Authorization of Anti-SARS-CoV-2 Monoclonal Antibodies for the Treatment of COVID-19. Last Updated: April 8, 2021 https://www.covid19treatmentguidelines.nih.gov/statement-on-anti-sars-cov-2-monoclonal-antibodies-eua/
- ↑ 9.0 9.1 9.2 NIH COVID-19 Treatment Guidelimes. April 21, 2021 Anti-SARS-CoV-2 Monoclonal Antibodies. https://www.covid19treatmentguidelines.nih.gov/anti-sars-cov-2-antibody-products/anti-sars-cov-2-monoclonal-antibodies/
- ↑ Basen R, D'Ambrosio A COVID-19 Treatments: What's In, What's Out. A look at which treatments are effective -- and which aren't. MedPage Today March 17, 2021 https://www.medpagetoday.com/special-reports/exclusives/91680
- ↑ 11.0 11.1 11.2 Walker M U.S. Pauses Use of Lilly's Monoclonal Antibody Combo for COVID. Bamlanivimab and etesevimab not active against all viral strains. MedPage Today June 28, 2021 https://www.medpagetoday.com/infectiousdisease/covid19/93313
- ↑ 12.0 12.1 Fiore K What Doctors Should Know About Delta. Here's the latest on transmissibility, virulence, vaccine efficacy, and more. MedPage Today June 29, 2021 https://www.medpagetoday.com/special-reports/exclusives/93351
- ↑ Dolgin E 'Super-antibodies' could curb COVID-19 and help avert future pandemics. Nature Biotechnology 2021 39:783-785. June 22 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34158667 PMCID: PMC8218965 Free PMC article https://www.nature.com/articles/s41587-021-00980-x
- ↑ 14.0 14.1 Abbasi J Uberantibodies From Recovered COVID-19 Patients Could Spur New Therapeutics and Vaccines. JAMA. Published online July 28, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34319350 https://jamanetwork.com/journals/jama/fullarticle/2782673
Wang L, Zhou T, Zhang Y et al Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants. Science 01 Jul 2021: PMID: https://www.ncbi.nlm.nih.gov/pubmed/34210892 https://science.sciencemag.org/content/early/2021/06/30/science.abh1766 - ↑ 15.0 15.1 Kramer KJ, Johnson NV, Shiakolas AR et al Potent neutralization of SARS-CoV-2 variants of concern by an antibody with an uncommon genetic signature and structural mode of spike recognition. Cell Reports. Sept 15, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34592170 PMCID: PMC8443366 Free PMC article https://www.cell.com/cell-reports/fulltext/S2211-1247(21)01243-2
- ↑ 16.0 16.1 American Medical Association (AMA) AMA Morning Rounds. Jan 25, 2022
- ↑ 17.0 17.1 17.2 O'Mary L COVID-19 Monoclonal Antibody Treatments No Longer Effective. Medscape. Dec 5, 2022 https://www.medscape.com/viewarticle/985001