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monoclonal antibody to spike glycoprotein of SARS-CoV2 (COVID-19)

bamlanivimab/etesevimab, casirivimab/imdevimab, & sotrovimab Indications: - treatment of outpatients with COVID-19* >= 14 years of age >= 40 kg - especially adults >= 65 years with COVID-19 at risk for severe disease * 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 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] - details of study & pharmacology of antibody(s) not revealed [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] Dosage: - Bamlanivimab (700 mg) plus etesevimab (1400 mg) once by IV infusion - Casirivimab (1200 mg) plus imdevimab (1200 mg) once by IV infusion [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]

Interactions

drug adverse effects of pharmaceutical monoclonal antibodies

Specific

'bebtelovimab bamlanivimab (LY-CoV555) casirivimab cilgavimab cilgavimab/tixagevimab (Evusheld, AZD7442) etesevimab imdevimab pemivibart (Pemgarda) S309 monoclonal antibody sotrovimab tixagevimab VIR-7831

General

pharmaceutical monoclonal antibody antiviral agent

References

  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
  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: 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: 33356051 https://www.nejm.org/doi/full/10.1056/NEJMoa2033130
  3. 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: 33332778 https://www.nejm.org/doi/full/10.1056/NEJMoa2035002 - Regeneron Pharmaceuticals. Jan 26, 2021 Regeneron Reports Positive Interim Data with REGEN-COV 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. 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: 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: 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. 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: 32422645 https://www.nature.com/articles/s41586-020-2349-y
  6. 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. 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. 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. 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/
  10. 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. 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. 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
  13. Dolgin E 'Super-antibodies' could curb COVID-19 and help avert future pandemics. Nature Biotechnology 2021 39:783-785. June 22 PMID: 34158667 PMCID: PMC8218965 Free PMC article https://www.nature.com/articles/s41587-021-00980-x
  14. Abbasi J Uberantibodies From Recovered COVID-19 Patients Could Spur New Therapeutics and Vaccines. JAMA. Published online July 28, 2021 PMID: 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: 34210892 https://science.sciencemag.org/content/early/2021/06/30/science.abh1766
  15. 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: 34592170 PMCID: PMC8443366 Free PMC article https://www.cell.com/cell-reports/fulltext/S2211-1247(21)01243-2
  16. American Medical Association (AMA) AMA Morning Rounds. Jan 25, 2022
  17. O'Mary L COVID-19 Monoclonal Antibody Treatments No Longer Effective. Medscape. Dec 5, 2022 https://www.medscape.com/viewarticle/985001