Sotrovimab

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Sotrovimab
A vial of sotrovimab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetSpike protein of SARS-CoV-2
Names
Trade namesXevudy
Other namesVIR-7831, GSK4182136
Clinical data
Pregnancy
category
Routes of
use		Intravenous
Typical dose500 mg[2]
External links
AHFS/Drugs.comMonograph
Legal
License data
Legal status
  • AU: S4 (Prescription only) [1][3][4]
  • US: Unapproved; Emergency Use Authorization [5]

Sotrovimab, sold under the brand name Xevudy, is a medication which was used to treat COVID-19 in people who do not need supplemental oxygen but are a high risk of getting severe disease.[2] In this group it decreased the need for hospitalization.[6] It; however, does not appear effective for Omicron BA.2 subvariant and is not recommended in regions were this makes up more than half of cases.[7][8][9] It is given by gradual injection into a vein.[2]

Common side effects include allergic reactions including anaphylaxis.[2] Anaphylaxis occurs in about 1 in 2,000 people.[2] Safety in pregnancy or breastfeeding is unclear.[5] It is a monoclonal antibody which attaches to the spike protein of SARS-CoV-2 making the virus unable to enter the body’s cells.[2]

Sotrovimab was approved for medical use in Europe in 2021.[2] It has Emergency Use Authorization (EUA) in the United States as of 2021.[5] In the United States it costs 2,100 USD per dose, with this amount paid by the the United States government.[10]

Medical uses

In the European Union, sotrovimab is indicated for the treatment of COVID-19 in people aged twelve years of age and older and weighing at least 40 kilograms (88 lb) who do not require supplemental oxygen and who are at increased risk of the disease becoming severe.[2] It needs to be used within 5 days of the onset of symptoms.[2] It is not used in people who need oxygen or hospitalization.[5] It is believed to remain effective for the omicron variant.[7]

Those at high risk of worsening include:[5]

Dosage

It is given as a dose of 500 mg into a vein.[2] It is given over 30 minutes.[5]

Mechanism of action

Sotrovimab is designed to attach to the spike protein of SARS-CoV-2.[11][12] [13] Sotrovimab has demonstrated activity via two antiviral mechanisms in vitro, antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).[14]

History

It is under development by GlaxoSmithKline and Vir Biotechnology, Inc.[11][15]

Sotrovimab was derived from a parent antibody (S309) first isolated in 2003 from memory B cells taken from an individual who had recovered from the Severe Acute Respiratory Syndrome (SARS).[16][17] The S309 parent antibody targets the spike (S) glycoprotein, which promotes the entry of SARS-Cov-2 into host cells and is the main target of neutralizing antibodies.[18] Using electron microscopy and binding assays, S309 was shown to recognize an epitope containing the N343 glycan that is highly conserved within the Sarbecovirus subgenus in a region that does not compete with angiotensin-converting enzyme 2 (ACE2) binding.[18] This epitope does not overlap with mutations observed in current SARS-Cov-2 variants of concern[17] and, in a preprint, sotrovimab was shown to bind in vitro to SARS-CoV-2 variants, including the beta variant first identified in South Africa (known as B.1.351 or 501Y.V2).[17]

Sotrovimab has been engineered to possess an Fc LS mutation (M428L/N434S) that confers enhanced binding to the neonatal Fc receptor[19] resulting in an extended half-life and potentially enhanced drug distribution to the lungs.[14]

Society and culture

Economics

In 2021, the United States government agreed to purchase 1.5 million doses of the drug at $2,100 per dose.[10]

Authorization

On May 21, 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) completed its review on the use of sotrovimab for the treatment of COVID‑19. It concluded that sotrovimab can be used to treat confirmed COVID-19 in adults and adolescents (aged 12 years and above and weighing at least 40 kg) who do not require supplemental oxygen and who are at risk of progressing to severe COVID-19.[20] A rolling review of sotrovimab will continue and once finalized will be the basis for an EU marketing authorisation application for this medicine.

On May 26, 2021, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for sotrovimab for the treatment of mild-to-moderate COVID-19 in people aged aged 12 years and above weighing at least 40 kilograms (88 lb) with positive results of direct SARS-CoV-2 viral testing and who are at high risk for progression to severe COVID-19, including hospitalization or death.[21][22][23][24]

It was approved in Canada in July 2021.[25]

In August 2021, sotrovimab was granted provisional approval for the treatment of COVID-19 in Australia.[3]

In December 2021, the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom has approved sotrovimab for use in people aged 12 years and over.[26]

Research

Sotrovimab is being evaluated in the following clinical trials:[14]

Sotrovimab has not been evaluated in a Phase 1 study.[14]

The pivotal COMET-ICE study is an ongoing, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of sotrovimab in adults with confirmed COVID-19 (mild, early disease with less than 5 days of symptoms) at risk of disease progression.

A planned interim analysis of this study reported that sotrovimab reduced the risk of hospitalization for more than 24 hours or death by 85% compared with placebo. Overall 1% of patients receiving sotrovimab died or required hospitalization for more than 24 hours compared to 7% of patients treated with placebo.[20] The study is ongoing and preliminary results have been published in the New England Journal of Medicine.[27]

References

  1. ↑ 1.0 1.1 "Xevudy". Therapeutic Goods Administration (TGA). 20 August 2021. Archived from the original on 18 September 2021. Retrieved 17 September 2021.
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 "Xevudy EPAR". European Medicines Agency (EMA). 15 December 2021. Archived from the original on 18 December 2021. Retrieved 17 December 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  3. ↑ 3.0 3.1 "TGA provisionally approves GlaxoSmithKline's COVID-19 treatment: sotrovimab (Xevudy)". Therapeutic Goods Administration (TGA) (Press release). 20 August 2021. Archived from the original on 4 September 2021. Retrieved 4 September 2021.
  4. ↑ "COVID-19 treatment: GlaxoSmithKline Australia Pty Ltd, sotrovimab (Xevudy)". Therapeutic Goods Administration (TGA). 20 August 2021. Archived from the original on 23 October 2021. Retrieved 22 October 2021.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 "Sotrovimab injection, solution, concentrate". DailyMed. Archived from the original on 7 July 2021. Retrieved 15 June 2021.
  6. ↑ "Treatments". www.bccdc.ca. Archived from the original on 9 October 2021. Retrieved 4 January 2022.
  7. ↑ 7.0 7.1 "Statement on Therapies for High-Risk, Nonhospitalized Patients". COVID-19 Treatment Guidelines. Archived from the original on 7 January 2022. Retrieved 6 January 2022.
  8. ↑ Kreier, Freda (23 February 2022). "Will a rising Omicron variant scramble antibody treatments?". Nature: d41586–022–00419-6. doi:10.1038/d41586-022-00419-6.
  9. ↑ "FDA updates Sotrovimab emergency use authorization". FDA. Archived from the original on 28 March 2022. Retrieved 30 March 2022.
  10. ↑ 10.0 10.1 "After slow start, demand for COVID monoclonal antibodies treatment skyrockets". USA Today. 25 August 2021. Archived from the original on 18 December 2021. Retrieved 18 December 2021.
  11. ↑ 11.0 11.1 "EMA starts rolling review of sotrovimab (VIR-7831) for COVID-19". European Medicines Agency (EMA) (Press release). 7 May 2021. Archived from the original on 3 August 2021. Retrieved 21 May 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  12. ↑ "EMA issues advice on use of sotrovimab (VIR-7831) for treating COVID-19". European Medicines Agency (EMA) (Press release). 21 May 2021. Archived from the original on 29 July 2021. Retrieved 21 May 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  13. ↑ "EMA starts review of VIR-7831 for treating patients with COVID-19". European Medicines Agency (EMA) (Press release). 15 April 2021. Archived from the original on 22 May 2021. Retrieved 21 May 2021.
  14. ↑ 14.0 14.1 14.2 14.3 "Assessment Report: Use of sotrovimab for the treatment of COVID-19" (PDF). European Medicines Agency. May 2021. Archived (PDF) from the original on 28 July 2021. Retrieved 2 December 2021.
  15. ↑ "GSK and Vir Biotechnology announce the start of the EMA rolling review of VIR-7831 (sotrovimab) for the early treatment of COVID-19". GlaxoSmithKline (Press release). 7 May 2021. Archived from the original on 22 May 2021. Retrieved 21 May 2021.
  16. ↑ Ledford H (March 2021). "COVID antibody treatments show promise for preventing severe disease". Nature. 591 (7851): 513–514. Bibcode:2021Natur.591..513L. doi:10.1038/d41586-021-00650-7. PMID 33712752. S2CID 232218189.
  17. ↑ 17.0 17.1 17.2 Cathcart AL, Havenar-Daughton C, Lempp FA, Ma D, Schmid M, Agostini ML, et al. (2021). "The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and 3 in vivo activity against SARS-CoV-2". bioRxiv: Preprint. doi:10.1101/2021.03.09.434607. S2CID 232223983. Archived from the original on 5 August 2021. Retrieved 2 December 2021.
  18. ↑ 18.0 18.1 Pinto D, Park YJ, Beltramello M, Walls AC, Tortorici MA, Bianchi S, et al. (July 2020). "Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody". Nature. 583 (7815): 290–295. Bibcode:2020Natur.583..290P. doi:10.1038/s41586-020-2349-y. PMID 32422645. S2CID 218691958.
  19. ↑ Saunders KO (2019). "Conceptual Approaches to Modulating Antibody Effector Functions and Circulation Half-Life". Frontiers in Immunology. 10: 1296. doi:10.3389/fimmu.2019.01296. PMC 6568213. PMID 31231397.
  20. ↑ 20.0 20.1 "EMA issues advice on use of sotrovimab (VIR-7831) for treating COVID-19". European Medicines Agency. May 2021. Archived from the original on 29 July 2021. Retrieved 2 December 2021.
  21. ↑ "Coronavirus (COVID-19) Update: FDA Authorizes Additional Monoclonal Antibody for Treatment of COVID-19". U.S. Food and Drug Administration (FDA) (Press release). 26 May 2021. Archived from the original on 6 August 2021. Retrieved 26 May 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  22. ↑ "Emergency Use Authorization 100: Sotrovimab". U.S. Food and Drug Administration (FDA). 28 May 2021. Archived from the original on 10 June 2021. Retrieved 2 December 2021.
  23. ↑ "Fact Sheet for Healthcare Providers Emergency Use Authorization (Eua) of Sotrovimab". U.S. Food and Drug Administration (FDA). 2021. Archived from the original on 31 July 2021. Retrieved 2 December 2021.
  24. ↑ "Frequently Asked Questions on the Emergency Use Authorization of Sotrovimab". U.S. Food and Drug Administration (FDA). 26 May 2021. Archived from the original on 7 July 2021. Retrieved 2 December 2021.
  25. ↑ Canada, Health (17 September 2020). "Drug and vaccine authorizations for COVID-19: List of applications received". www.canada.ca. Archived from the original on 18 March 2021. Retrieved 6 January 2022.
  26. ↑ "UK approves another antibody treatment for Covid". BBC News. 2 December 2021. Archived from the original on 2 December 2021. Retrieved 2 December 2021.
  27. ↑ Gupta, Anil; Gonzalez-Rojas, Yaneicy; Juarez, Erick; Crespo Casal, Manuel; Moya, Jaynier; Falci, Diego R.; Sarkis, Elias; Solis, Joel; Zheng, Hanzhe; Scott, Nicola; Cathcart, Andrea L.; Hebner, Christy M.; Sager, Jennifer; Mogalian, Erik; Tipple, Craig; Peppercorn, Amanda; Alexander, Elizabeth; Pang, Phillip S.; Free, Almena; Brinson, Cynthia; Aldinger, Melissa; Shapiro, Adrienne E.; COMET-ICE Investigators (18 November 2021). "Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab". New England Journal of Medicine. 385 (21): 1941–1950. doi:10.1056/NEJMoa2107934. PMID 34706189. S2CID 240074048. Archived from the original on 5 December 2021. Retrieved 28 November 2021.

External links

External sites:
Identifiers:
  1. ↑ "New ATC 5th levels". WHOCC. Archived from the original on 28 November 2021. Retrieved 2 December 2021.
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