Bamlanivimab

Last updated
Bamlanivimab
Monoclonal antibody
Type Whole antibody
Source Human
Target Spike protein of SARS-CoV-2
Clinical data
Pronunciation /ˌbæmləˈnɪvɪmæb/ BAM-lə-NIV-i-mab [1]
Other namesLY-CoV555, LY3819253
AHFS/Drugs.com Monograph
License data
Routes of
administration
Intravenous
ATC code
  • None
Legal status
Legal status
Identifiers
CAS Number
DrugBank
UNII
KEGG

Bamlanivimab is a monoclonal antibody developed by AbCellera Biologics and Eli Lilly as a treatment for COVID-19. [7] The medication was granted an emergency use authorization (EUA) by the US Food and Drug Administration (FDA) in November 2020, [8] [9] [10] and the EUA was revoked in April 2021. [11]

Contents

Bamlanivimab is an IgG1 monoclonal antibody (mAb) directed against the spike protein of SARS-CoV-2. [12] The aim is to block viral attachment and entry into human cells, thus neutralizing the virus, and help preventing and treating COVID-19. [7]

Bamlanivimab emerged from the collaboration between Lilly and AbCellera to create antibody therapies for the prevention and treatment of COVID-19. [7]

Bamlanivimab is also used as part of the bamlanivimab/etesevimab combination that was granted an EUA by the FDA. [13] [14] [15]

In June 2021, the US Office of the Assistant Secretary for Preparedness and Response (ASPR) paused distribution of bamlanivimab and etesevimab together, and etesevimab alone (to pair with existing supply of bamlanivimab), due to the increase of circulating variants. [16] [17] [18]

Studies

Bamlanivimab has been studied in several trials. Some initial results on bamlanivimab seemed promising, with one review saying that it "decrease[s] viral load when given early on in the course of SARS-CoV-2 infection and favourably impact[s] clinical outcomes for patients with mild-to-moderate COVID-19". [19] However, further results have not shown any clinically relevant benefit. [12] [20]

Animal trials

An initial trial tested bamlanivimab in rhesus monkeys. Administration of the drug reduced SARS-CoV-2 replications in the upper and lower respiratory tract of monkeys. [21]

Following these results in a non-human primate model, several human studies were initiated.[ citation needed ]

Human trials

BLAZE-1 Trial

The Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies (BLAZE-1) trial was sponsored by the drug's developer Eli Lilly. [22] The drug was tested in SARS-CoV-2 patients who did not require hospitalization. While an interim analysis suggested reduced ER visits and hospitalizations, this difference was not statistically significant in the final analysis. [20] A subsequent analysis demonstrated superior efficacy of a combination of bamlanivimab and etesevimab compared to placebo. [23]

ACTIV-2 Trial

This study is sponsored by the NIH, examining bamlanivimab administration to SARS-CoV-2 patients in the outpatient setting. The study is ongoing and no data have been released yet. [24]

ACTIV-3 Trial

This study specifically examined bamlanivimab in hospitalized COVID-19 patients without severe illness (e.g. end organ damage); these patients were also receiving the standard of care at the time including supportive care, remdesivir, supplemental oxygen, and dexamethasone as indicated. Enrollment was stopped early due to futility; bamlanivimab was not found to increase sustained recovery (90 days), and did not change pulmonary function. The study was funded by Operation Warp Speed. [25] [26]

Authorization

On 7 October 2020, Eli Lilly and Company submitted a request for an Emergency Use Authorization (EUA) to the U.S. Food and Drug Administration (FDA) for LY-CoV555 monotherapy in higher-risk people who have been diagnosed with mild-to-moderate COVID-19. This authorization was largely done on the basis of the interim BLAZE-1 results showing possible benefit. However, further data obtained after the EUA was granted have not shown any clinically relevant benefit from bamlanivimab. [7] [12]

On 9 November 2020, bamlanivimab was granted an emergency use authorization by the US Food and Drug Administration (FDA) for the treatment of mild-to-moderate COVID-19 in adults and adolescents. Bamlanivimab is authorized for people with positive results of direct SARS-CoV-2 viral testing who are twelve years of age and older weighing at least 40 kilograms (88 lb), and who are at high risk for progressing to severe COVID-19 or hospitalization. This includes those who are 65 years of age or older, or who have certain chronic medical conditions. [27]

On 16 April 2021, the FDA revoked the emergency use authorization (EUA) that allowed for the investigational monoclonal antibody therapy bamlanivimab, when administered alone, to be used for the treatment of mild-to-moderate COVID-19. [11]

Bamlanivimab/etesevimab

On 9 February 2021, the FDA issued an emergency use authorization (EUA) for bamlanivimab and etesevimab administered together for the treatment of mild to moderate COVID-19 in people twelve years of age or older weighing at least 40 kilograms (88 lb) who test positive for SARS‑CoV‑2 and who are at high risk for progressing to severe COVID-19. The authorized use includes treatment for those who are 65 years of age or older or who have certain chronic medical conditions. [28]

On 1 February 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) started rolling reviews of data on the use of the monoclonal antibodies casirivimab/imdevimab, bamlanivimab/etesevimab, and bamlanivimab for the treatment of COVID-19. [29] On 29 October 2021, Eli Lilly withdrew bamlanivimab and etesevimab from the European Medicines Agency rolling review process. [30]

Deployment

On 28 October 2020, Eli Lilly and Company announced that it had struck a deal with the US government to supply 300,000 vials of bamlanivimab 700 mg for US$375 million. [7]

Society and culture

Names

Bamlanivimab is the international nonproprietary name (INN). [31]

Related Research Articles

<span class="mw-page-title-main">Eli Lilly and Company</span> American pharmaceutical company

Eli Lilly and Company is an American pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 countries. The company was founded in 1876 by, and named after, Colonel Eli Lilly, a pharmaceutical chemist and veteran of the American Civil War.

<span class="mw-page-title-main">Regeneron Pharmaceuticals</span> American biotechnology company

Regeneron Pharmaceuticals, Inc. is an American biotechnology company headquartered in Westchester County, New York. The company was founded in 1988. Originally focused on neurotrophic factors and their regenerative capabilities, giving rise to its name, the company then branched out into the study of both cytokine and tyrosine kinase receptors, which gave rise to their first product, which is a VEGF-trap.

An Emergency Use Authorization (EUA) in the United States is an authorization granted to the Food and Drug Administration (FDA) under sections of the Federal Food, Drug, and Cosmetic Act as added to and amended by various Acts of Congress, including by the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 (PAHPRA), as codified by 21 U.S.C. § 360bbb-3, to allow the use of a drug prior to approval. It does not constitute approval of the drug in the full statutory meaning of the term, but instead authorizes the FDA to facilitate availability of an unapproved product, or an unapproved use of an approved product, during a declared state of emergency from one of several agencies or of a "material threat" by the Secretary of Homeland Security.

<span class="mw-page-title-main">Baricitinib</span> Chemical compound

Baricitinib, sold under the brand name Olumiant among others, is an immunomodulatory medication used for the treatment of rheumatoid arthritis, alopecia areata, and COVID-19. It acts as an inhibitor of janus kinase (JAK), blocking the subtypes JAK1 and JAK2.

QuidelOrtho Corporation is a major American manufacturer of diagnostic healthcare products that are sold worldwide.

<span class="mw-page-title-main">Remdesivir</span> Antiviral drug

Remdesivir, sold under the brand name Veklury, is a broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences. It is administered via injection into a vein. During the COVID‑19 pandemic, remdesivir was approved or authorized for emergency use to treat COVID‑19 in numerous countries.

AbCellera Biologics Inc. is a Vancouver, British Columbia-based biotechnology firm that researches and develops human antibodies. The company is best known for its leading role in the Pandemic Prevention Platform, a project of DARPA's Biological Technologies Office. AbCellera utilizes a proprietary technology platform, which they claim can develop "medical countermeasures within 60 days." Its platform for single-cell screening was initially developed at the University of British Columbia.

<span class="mw-page-title-main">COVID-19 drug development</span> Preventative and therapeutic medications for COVID-19 infection

COVID-19 drug development is the research process to develop preventative therapeutic prescription drugs that would alleviate the severity of coronavirus disease 2019 (COVID-19). From early 2020 through 2021, several hundred drug companies, biotechnology firms, university research groups, and health organizations were developing therapeutic candidates for COVID-19 disease in various stages of preclinical or clinical research, with 419 potential COVID-19 drugs in clinical trials, as of April 2021.

<span class="mw-page-title-main">Convalescent plasma</span> Blood plasma from disease survivor

Convalescent plasma is the blood plasma collected from a survivor of an infectious disease. This plasma contains antibodies specific to a pathogen and can be used therapeutically by providing passive immunity when transfusing it to a newly infected patient with the same condition. Convalescent plasma can be transfused as it has been collected or become the source material for the hyperimmune serum which consists largely of IgG but also includes IgA and IgM. or as source material for anti-pathogen monoclonal antibodies, Collection is typically achieved by apheresis, but in low-to-middle income countries, the treatment can be administered as convalescent whole blood.

Jason S. McLellan is a structural biologist, professor in the Department of Molecular Biosciences and Robert A. Welch Chair in Chemistry at The University of Texas at Austin who specializes in understanding the structure and function of viral proteins, including those of coronaviruses. His research focuses on applying structural information to the rational design of vaccines and other therapies for viruses, including SARS-CoV-2, the novel coronavirus that causes COVID-19, and respiratory syncytial virus (RSV). McLellan and his team collaborated with researchers at the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center to design a stabilized version of the SARS-CoV-2 spike protein, which biotechnology company Moderna used as the basis for the vaccine mRNA-1273, the first COVID-19 vaccine candidate to enter phase I clinical trials in the U.S. At least three other vaccines use this modified spike protein: those from Pfizer and BioNTech; Johnson & Johnson and Janssen Pharmaceuticals; and Novavax.

Although several medications have been approved in different countries as of April 2022, not all countries have these medications. Patients with mild to moderate symptoms who are in the risk groups can take nirmatrelvir/ritonavir or remdesivir, either of which reduces the risk of serious illness or hospitalization. In the US, the Biden Administration COVID-19 action plan includes the Test to Treat initiative, where people can go to a pharmacy, take a COVID test, and immediately receive free Paxlovid if they test positive.

<span class="mw-page-title-main">Casirivimab/imdevimab</span> Antiviral combination medication

Casirivimab/imdevimab, sold under the brand name REGEN‑COV among others, is a combination medicine used for the treatment and prevention of COVID‑19. It consists of two human monoclonal antibodies, casirivimab and imdevimab that must be mixed together and administered as an infusion or subcutaneous injection. The combination of two antibodies is intended to prevent mutational escape. It is also available as a co-formulated product. It was developed by the American biotechnology company Regeneron Pharmaceuticals.

Bamlanivimab/etesevimab is a combination of two monoclonal antibodies, bamlanivimab and etesevimab, administered together via intravenous infusion as a treatment for COVID-19. Both types of antibody target the surface spike protein of SARS‑CoV‑2.

<span class="mw-page-title-main">Chloroquine and hydroxychloroquine during the COVID-19 pandemic</span> Early experimental treatment efforts during the start of COVID-19 pandemic

Chloroquine and hydroxychloroquine are anti-malarial medications also used against some auto-immune diseases. Chloroquine, along with hydroxychloroquine, was an early experimental treatment for COVID-19. Neither drug prevents SARS-CoV-2 infection.

<span class="mw-page-title-main">Sotrovimab</span> Monoclonal antibody

Sotrovimab, sold under the brand name Xevudy, is a human neutralizing monoclonal antibody with activity against severe acute respiratory syndrome coronavirus 2, known as SARS-CoV-2. It was developed by GlaxoSmithKline and Vir Biotechnology, Inc. Sotrovimab is designed to attach to the spike protein of SARS-CoV-2.

<span class="mw-page-title-main">Tixagevimab/cilgavimab</span> Monoclonal antibody treatment for COVID-19

Tixagevimab/cilgavimab, sold under the brand name Evusheld, is a combination of two human monoclonal antibodies, tixagevimab (AZD8895) and cilgavimab (AZD1061) targeted against the surface spike protein of SARS-CoV-2 used to prevent COVID-19. It is being developed by British-Swedish multinational pharmaceutical and biotechnology company AstraZeneca. It is co-packaged and given as two separate consecutive intramuscular injections.

<span class="mw-page-title-main">John R. Mascola</span> American Physician-Scientist

John R. Mascola is an American physician-scientist, immunologist and infectious disease specialist. He was the director of the Vaccine Research Center (VRC), part of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). He also served as a principal advisor to Anthony Fauci, director of NIAID, on vaccines and biomedical research affairs. Mascola is the current Chief Scientific Officer for ModeX Therapeutics.

Bebtelovimab is a monoclonal antibody developed by AbCellera and Eli Lilly as a treatment for COVID-19.

Vilobelimab, sold under the brand name Gohibic, is an investigational medication that is used for the treatment of COVID-19. It is a human-mouse chimeric IgG4 kappa antibody that targets human C5a in plasma.

References

  1. "What is bamlanivimab". Eli Lilly. Retrieved 16 December 2020.
  2. "Regulatory Decision Summary - Bamlanivimab". Health Canada . 20 November 2020. Retrieved 13 December 2020.
  3. "Bamlanivimab (bamlanivimab)". Health Canada . 20 November 2020. Retrieved 13 December 2020.
  4. "Bamlanivimab Product information". Health Canada . 25 April 2012. Retrieved 13 December 2020.
  5. "Summary Basis of Decision (SBD) for Bamlanivimab". Health Canada . 23 October 2014. Retrieved 29 May 2022.
  6. "Bamlanivimab injection, solution". DailyMed. Retrieved 4 January 2022.
  7. 1 2 3 4 5 "Lilly announces agreement with U.S. government to supply 300,000 vials of investigational neutralizing antibody bamlanivimab (LY-CoV555) in an effort to fight COVID-19" (Press release). Eli Lilly and Company. October 28, 2020.
  8. "Fact Sheet For Health Care Providers Emergency Use Authorization (EUA) Of Bamlanivimab" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 18 March 2021.
  9. "Emergency Use Authorization (EUA) for the Treatment of COVID-19". Eli Lilly and Company. 9 November 2020. Retrieved 18 March 2021.
  10. Hinton DM (2 March 2021). "Emergency Use Authorization 090" (PDF). U.S. Food and Drug Administration.
  11. 1 2 "Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for Monoclonal Antibody Bamlanivimab". U.S. Food and Drug Administration (FDA) (Press release). 16 April 2021. Retrieved 16 April 2021.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  12. 1 2 3 "Lilly provides comprehensive update on progress of SARS-CoV-2 neutralizing antibody programs". Eli Lilly and Company. 7 October 2020. Retrieved 26 October 2020.
  13. "Fact Sheet For Health Care Providers Emergency Use Authorization (EUA) Of Bamlanivimab and Etesevimab" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 18 March 2021.
  14. "Bamlanivimab and etesevimab EUA". Eli Lilly and Company. 9 February 2021. Retrieved 18 March 2021.
  15. Hinton DM (16 September 2021). "Emergency Use Authorization 094" (PDF). U.S. Food and Drug Administration.
  16. "Pause in the Distribution of bamlanivimab/etesevimab". U.S. Department of Health and Human Services. 25 June 2021.
  17. "Important Update on the Distribution of Bamlanivimab/etesevimab". U.S. Department of Health and Human Services. 16 June 2021.
  18. "Bamlanivimab and etesevimab Emergency Use Authorization (EUA) for COVID-19". Lilly COVID-19. Retrieved 2 July 2021.
  19. Taylor PC, Adams AC, Hufford MM, de la Torre I, Winthrop K, Gottlieb RL (June 2021). "Neutralizing monoclonal antibodies for treatment of COVID-19". Nature Reviews. Immunology. 21 (6): 382–393. doi:10.1038/s41577-021-00542-x. PMC   8054133 . PMID   33875867.
  20. 1 2 Chen P, Nirula A, Heller B, Gottlieb RL, Boscia J, Morris J, et al. (January 2021). "SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19". The New England Journal of Medicine. 384 (3): 229–237. doi:10.1056/NEJMoa2029849. ISSN   0028-4793. PMC   7646625 . PMID   33113295.
  21. Jones BE, Brown-Augsburger PL, Corbett KS, Westendorf K, Davies J, Cujec TP, et al. (October 2020). "LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection". bioRxiv. doi:10.1101/2020.09.30.318972. PMC   7536866 . PMID   33024963.
  22. Clinical trial number NCT04427501 for "A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Participants With Mild to Moderate COVID-19 Illness" at ClinicalTrials.gov
  23. Dougan M, Nirula A, Azizad M, Mocherla B, Gottlieb RL, Chen P, et al. (October 2021). "Bamlanivimab plus Etesevimab in Mild or Moderate Covid-19". The New England Journal of Medicine. 385 (15): 1382–1392. doi:10.1056/NEJMoa2102685. PMC   8314785 . PMID   34260849.
  24. Clinical trial number NCT04518410 for "ACTIV-2: A Study for Outpatients With COVID-19" at ClinicalTrials.gov
  25. "Statement – NIH-Sponsored ACTIV-3 Trial Closes LY-CoV555 Sub-Study | NIH: National Institute of Allergy and Infectious Diseases". www.niaid.nih.gov. 26 October 2020. Retrieved 2021-01-24.
  26. Lundgren JD, Grund B, Barkauskas CE, Holland TL, Gottlieb RL, Sandkovsky U, et al. (March 2021). "A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19". The New England Journal of Medicine. 384 (10): 905–914. doi:10.1056/NEJMoa2033130. PMC   7781100 . PMID   33356051.
  27. "FDA Authorizes Monoclonal Antibody for Treatment of COVID-19". U.S. Food and Drug Administration (FDA) (Press release). 9 November 2020. Retrieved 10 December 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  28. "FDA Authorizes Monoclonal Antibodies for Treatment of COVID-19". U.S. Food and Drug Administration (FDA) (Press release). 10 February 2021. Retrieved 9 February 2021.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  29. "EMA reviewing data on monoclonal antibody use for COVID-19" (Press release). European Medicines Agency (EMA). 4 February 2021. Retrieved 4 March 2021.
  30. "Bamlanivimab and etesevimab for COVID-19: Withdrawn application". European Medicines Agency (EMA) (Press release). 2 November 2021. Retrieved 24 April 2022.
  31. World Health Organization (2020). "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 124 – COVID-19 (special edition)" (PDF). WHO Drug Information. 34 (3): 645–646. Retrieved 23 November 2020.