Sotrovimab Explained

Type:mab
Mab Type:mab
Source:u
Target:Spike protein of SARS-CoV-2
Tradename:Xevudy
Dailymedid:Sotrovimab
Pregnancy Au:B2
Pregnancy Au Comment:[1]
Routes Of Administration:Intravenous
Atc Prefix:J06
Atc Suffix:BD05
Legal Au:S4
Legal Au Comment:[2] [3]
Legal Ca:Rx-only
Legal Ca Comment:/ Schedule D[4] [5]
Legal Uk:POM
Legal Us:Rx-only
Legal Us Comment:via emergency use authorization [6] [7]
Legal Eu:Rx-only
Cas Number:2423014-07-5
Iuphar Ligand:11333
Drugbank:DB16355
Unii:1MTK0BPN8V
Kegg:D12014
Synonyms:VIR-7831, GSK4182136

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.[8] [9] [10] It was developed by GlaxoSmithKline and Vir Biotechnology, Inc.[11] Sotrovimab is designed to attach to the spike protein of SARS-CoV-2.[12]

The most common side effects include hypersensitivity (allergic) reactions and infusion-related reactions.

Although Sotrovimab was used world-wide against SARS-CoV-2, including in the United States under an FDA emergency use authorization (EUA), the FDA canceled the EUA in April 2022 due to lack of efficacy against the Omicron variant.

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 40kg (90lb) who do not require supplemental oxygen and who are at increased risk of the disease becoming severe.

Sotrovimab is given by intravenous infusion, preferably within 5 days of onset of COVID-19 symptoms.[13]

Development and mechanism of action

Sotrovimab's development began in December 2019, at Vir Biotechnology when Vir scientists first learned of the initial COVID-19 outbreak in China.[14] Vir subsidiary Humabs BioMed had already compiled a library of frozen blood samples from patients infected with viral diseases, including two samples from patients infected with SARS-CoV-1. Vir scientists obtained samples of the novel SARS-CoV-2 virus and mixed them with various antibodies recovered from the old SARS-CoV-1 blood samples. The objective was to identify antibodies effective against both SARS-CoV-1 and SARS-CoV-2. This would imply that the antibodies were targeting highly conserved sequences and in turn would be more likely to remain effective against future variants of SARS-CoV-2. In April 2020, Lawrence Berkeley National Laboratory conducted a X-ray crystallography study at Vir's request to investigate how such antibodies bind to SARS-CoV-2 at the molecular level. The Berkeley Lab data helped Vir identify candidates for further study, and Vir eventually settled on a single candidate antibody, S309. Vir collaborated with GlaxoSmithKline to make various refinements to S309, resulting in sotrovimab.

Sotrovimab has been engineered to possess an Fc LS mutation (M428L/N434S) that confers enhanced binding to the neonatal Fc receptor[15] resulting in an extended half-life and potentially enhanced drug distribution to the lungs.[16]

Sotrovimab has demonstrated activity via two antiviral mechanisms in vitro, antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

Clinical efficacy

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 five days of symptoms) at risk of disease progression.

An 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 people receiving sotrovimab died or required hospitalization for more than 24 hours compared to 7% of people treated with placebo. The study is ongoing and preliminary results have been published in the New England Journal of Medicine.[17]

The full analysis of the COMET-ICE trial was published in JAMA and it showed that sotrovimab reduced risk of hospitalization for more than 24 hours or death by 79% compared to placebo (1% for sotrovoimab group and 6% for the placebo group). The trial involved 1057 participants and took place before the omicron variant was prevalent.[18]

Manufacturing

Sotrovimab is a biologic product which takes six months to manufacture in living cells. It is produced in Chinese hamster ovary cells.[19] At product launch in May 2021, sotrovimab's active pharmaceutical ingredient was produced by WuXi Biologics in China and sent to a GlaxoSmithKline plant in Parma, Italy for further processing into the finished product.[20] In January 2022, the spread of the SARS-CoV-2 Omicron variant began to render other monoclonal antibodies obsolete and caused global demand for sotrovimab to skyrocket. In response, Vir and GlaxoSmithKline announced they were working with Samsung Biologics on manufacturing sotrovimab at an additional site in South Korea.

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.[21]

Legal status

In May 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 twelve years and above and weighing at least 40kg (90lb)) who do not require supplemental oxygen and who are at risk of progressing to severe COVID-19. On 16 December 2021, the CHMP recommended authorizing sotrovimab for use in the EU[22] and authorization was granted the next day.[23]

In May 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 twelve years and above weighing at least 40kg (90lb) 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.[24] [25] [26]

In August 2021, sotrovimab was granted provisional approval for the treatment of COVID-19 in Australia.[27]

In September 2021, sotrovimab was granted special exception authorization in Japan.[28]

In December 2021, the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom approved sotrovimab for use in people aged twelve years of age and over who weigh more than 40kg (90lb).[29] [30] [31]

In March 2022, the FDA withdrew the EUA for sotrovimab in Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, Vermont, New Jersey, New York, Puerto Rico, the Virgin Islands, Illinois, Indiana, Michigan, Minnesota, Ohio, Wisconsin, Arizona, California, Hawaii, Nevada, American Samoa, Commonwealth of the Northern Mariana Islands, Federated States of Micronesia, Guam, Marshall Islands, Republic of Palau, Alaska, Idaho, Oregon, and Washington due to the high frequency of the Omicron BA.2 sub-variant and data showing that the authorized dose of sotrovimab is unlikely to be effective against that sub-variant.[32] [33] In April 2022, the FDA withdrew the EUA for sotrovimab.[34]

Research

Sotrovimab is being evaluated in the following clinical trials:

In March 2022, Australian virologists observed that sotrovimab may cause a drug-resistant mutation.[35]

External links

Notes and References

  1. Web site: Updates to the Prescribing Medicines in Pregnancy database . Therapeutic Goods Administration (TGA) . 12 May 2022 . 13 May 2022 . 3 April 2022 . https://web.archive.org/web/20220403064059/https://www.tga.gov.au/updates-prescribing-medicines-pregnancy-database . live .
  2. Web site: Xevudy . Therapeutic Goods Administration (TGA) . 20 August 2021 . 17 September 2021 . 18 September 2021 . https://web.archive.org/web/20210918050100/https://www.tga.gov.au/apm-summary/xevudy . live .
  3. Web site: COVID-19 treatment: GlaxoSmithKline Australia Pty Ltd, sotrovimab (Xevudy) . Therapeutic Goods Administration (TGA) . 20 August 2021 . 22 October 2021 . 23 October 2021 . https://web.archive.org/web/20211023060646/https://www.tga.gov.au/covid-19-treatment-glaxosmithkline-australia-pty-ltd-sotrovimab-xevudy . live .
  4. Web site: Summary Basis of Decision (SBD) for Sotrovimab . . 23 October 2014 . 29 May 2022 . 29 May 2022 . https://web.archive.org/web/20220529183108/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00548&lang=en . live .
  5. Web site: Sotrovimab (sotrovimab) . . 30 July 2021 . 31 May 2022 . 1 June 2022 . https://web.archive.org/web/20220601035708/https://covid-vaccine.canada.ca/sotrovimab/product-details . live .
  6. Web site: Sotrovimab injection, solution, concentrate . DailyMed . 15 June 2021 . 7 July 2021 . https://web.archive.org/web/20210707150556/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aa5cca2e-4351-4f81-b0e5-3303ac0b2474 . live .
  7. Web site: FDA updates Sotrovimab emergency use authorization . U.S. Food and Drug Administration (FDA) . 25 February 2022 . 27 February 2022 . 28 March 2022 . https://web.archive.org/web/20220328010007/https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-sotrovimab-emergency-use-authorization . live .
  8. Web site: Xevudy EPAR . European Medicines Agency (EMA) . 15 December 2021 . 17 December 2021 . 18 December 2021 . https://web.archive.org/web/20211218074403/https://www.ema.europa.eu/en/medicines/human/EPAR/xevudy . live . Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  9. EMA starts rolling review of sotrovimab (VIR-7831) for COVID-19. European Medicines Agency (EMA). 7 May 2021. 21 May 2021. 3 August 2021. https://web.archive.org/web/20210803145434/https://www.ema.europa.eu/en/news/ema-starts-rolling-review-sotrovimab-vir-7831-covid-19. live. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  10. EMA issues advice on use of sotrovimab (VIR-7831) for treating COVID-19. European Medicines Agency (EMA). 21 May 2021. 21 May 2021. 29 July 2021. https://web.archive.org/web/20210729113537/https://www.ema.europa.eu/en/news/ema-issues-advice-use-sotrovimab-vir-7831-treating-covid-19. live. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  11. GSK and Vir Biotechnology announce the start of the EMA rolling review of VIR-7831 (sotrovimab) for the early treatment of COVID-19 . GlaxoSmithKline . 7 May 2021 . 21 May 2021 . 22 May 2021 . https://web.archive.org/web/20210522174716/https://us.gsk.com/en-us/media/press-releases/gsk-and-vir-biotechnology-announce-the-start-of-the-ema-rolling-review-of-vir-7831-sotrovimab-for-the-early-treatment-of-covid-19/ . live .
  12. EMA starts review of VIR-7831 for treating patients with COVID-19 . European Medicines Agency (EMA) . 15 April 2021 . 21 May 2021 . 22 May 2021 . https://web.archive.org/web/20210522003507/https://www.ema.europa.eu/en/news/ema-starts-review-vir-7831-treating-patients-covid-19 . live .
  13. Web site: Xevudy 500 mg concentrate for solution for infusion – Summary of Product Characteristics (SmPC) – (emc) . 2022-05-24 . www.medicines.org.uk . 24 May 2022 . https://web.archive.org/web/20220524171909/https://www.medicines.org.uk/emc/product/13097/smpc . live .
  14. News: Krieger LM . How one person's cells led to our only antibody treatment for omicron . 24 January 2022 . The Mercury News . 23 January 2022 . 24 January 2022 . https://web.archive.org/web/20220124012904/https://www.mercurynews.com/2022/01/23/covid-how-one-persons-cells-led-to-our-only-antibody-treatment-for-omicron/ . live .
  15. Saunders KO . Conceptual Approaches to Modulating Antibody Effector Functions and Circulation Half-Life . Frontiers in Immunology . 10 . 1296 . 2019 . 31231397 . 6568213 . 10.3389/fimmu.2019.01296 . free .
  16. Web site: European Medicines Agency. May 2021. Assessment Report: Use of sotrovimab for the treatment of COVID-19. 28 July 2021. 28 July 2021. https://web.archive.org/web/20210728120137/https://www.ema.europa.eu/en/documents/referral/sotrovimab-also-known-vir-7831-gsk4182136-covid19-article-53-procedure-assessment-report_en.pdf. live.
  17. Gupta A, Gonzalez-Rojas Y, Juarez E, Crespo Casal M, Moya J, Falci DR, Sarkis E, Solis J, Zheng H, Scott N, Cathcart AL, Hebner CM, Sager J, Mogalian E, Tipple C, Peppercorn A, Alexander E, Pang PS, Free A, Brinson C, Aldinger M, Shapiro AE . Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab . The New England Journal of Medicine . 385 . 21 . 1941–1950 . November 2021 . 34706189 . 10.1056/NEJMoa2107934 . COMET-ICE Investigators . 240074048 . free .
  18. Gupta A, Gonzalez-Rojas Y, Juarez E, Crespo Casal M, Moya J, Rodrigues Falci D, Sarkis E, Solis J, Zheng H, Scott N, Cathcart AL, Parra S, Sager JE, Austin D, Peppercorn A, Alexander E, Yeh WW, Brinson C, Aldinger M, Shapiro AE . Effect of Sotrovimab on Hospitalization or Death Among High-risk Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial . JAMA . 327 . 13 . 1236–1246 . April 2022 . 35285853 . 8922199 . 10.1001/jama.2022.2832 . 3 April 2022 . live . https://web.archive.org/web/20220612041753/https://jamanetwork.com/journals/jama/fullarticle/2790246 . 12 June 2022 .
  19. Web site: Fact Sheet for Healthcare Providers Emergency Use Authorization (Eua) of Sotrovimab . U.S. Food and Drug Administration (FDA) . 2021 . 27 May 2021 . 31 July 2021 . https://web.archive.org/web/20210731054659/https://www.fda.gov/media/149534/download . live .
  20. News: Roland D . GlaxoSmithKline Racing to Provide Only Effective Covid-19 Antibody Treatment . 24 January 2022 . The Wall Street Journal . 21 January 2022 . 24 January 2022 . https://web.archive.org/web/20220124181507/https://www.wsj.com/articles/glaxosmithkline-racing-to-provide-only-effective-covid-19-antibody-treatment-11642770001 . live .
  21. News: After slow start, demand for COVID monoclonal antibodies treatment skyrockets . 18 December 2021 . USA Today . 25 August 2021 . 18 December 2021 . https://web.archive.org/web/20211218163655/https://www.usatoday.com/story/news/health/2021/08/25/monoclonal-antibodies-treatment-demand-skyrockets-covid-cases-climb/5579505001/ . live .
  22. 16 December 2021. COVID-19: EMA recommends authorisation of antibody medicine Xevudy. 19 December 2021. 19 December 2021. https://web.archive.org/web/20211219113238/https://www.ema.europa.eu/en/news/covid-19-ema-recommends-authorisation-antibody-medicine-xevudy. live.
  23. Web site: Xevudy . Union Register of medicinal products . 24 December 2021 . 25 December 2021 . https://web.archive.org/web/20211225013919/https://ec.europa.eu/health/documents/community-register/html/h1562.htm . live .
  24. Coronavirus (COVID-19) Update: FDA Authorizes Additional Monoclonal Antibody for Treatment of COVID-19 . U.S. Food and Drug Administration (FDA) . 26 May 2021 . 26 May 2021 . 6 August 2021 . https://web.archive.org/web/20210806211152/https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-monoclonal-antibody-treatment-covid-19 . live .
  25. Web site: Emergency Use Authorization 100: Sotrovimab . U.S. Food and Drug Administration (FDA) . 28 May 2021 . 27 May 2021 . 10 June 2021 . https://web.archive.org/web/20210610153116/https://www.fda.gov/media/149532/download . live .
  26. Web site: 26 May 2021 . Frequently Asked Questions on the Emergency Use Authorization of Sotrovimab . U.S. Food and Drug Administration (FDA) . 27 May 2021 . 7 July 2021 . https://web.archive.org/web/20210707150506/https://www.fda.gov/media/149535/download . live .
  27. TGA provisionally approves GlaxoSmithKline's COVID-19 treatment: sotrovimab (Xevudy) . Therapeutic Goods Administration (TGA) . 20 August 2021 . 4 September 2021 . 4 September 2021 . https://web.archive.org/web/20210904065216/https://www.tga.gov.au/media-release/tga-provisionally-approves-glaxosmithklines-covid-19-treatment-sotrovimab-xevudy . live .
  28. 1 January 2022 . GSK Received Approval for Monoclonal Antibody, "Xevudy for Intravenous Injection" (generic name: sotrovimab), for the treatment of COVID-19 . 27 September 2021 . 27 November 2021 . https://web.archive.org/web/20211127033053/https://jp.gsk.com/media/7512/20210927_xevudy-approval-e.pdf . live .
  29. News: 2 December 2021. UK approves another antibody treatment for Covid. BBC News Online. 2 December 2021. 2 December 2021. https://web.archive.org/web/20211202130031/https://www.bbc.com/news/health-59502745. live.
  30. MHRA approves Xevudy (sotrovimab), a COVID-19 treatment found to cut hospitalisation and death by 79% . Medicines and Healthcare products Regulatory Agency (MHRA) . 2 December 2021 . 24 December 2021 . 25 December 2021 . https://web.archive.org/web/20211225014103/https://www.gov.uk/government/news/mhra-approves-xevudy-sotrovimab-a-covid-19-treatment-found-to-cut-hospitalisation-and-death-by-79 . live .
  31. Web site: Regulatory approval of Xevudy (sotrovimab) . Medicines and Healthcare products Regulatory Agency (MHRA) . 2 December 2021 . 24 December 2021 . 25 December 2021 . https://web.archive.org/web/20211225014107/https://www.gov.uk/government/publications/regulatory-approval-of-xevudy-sotrovimab . live .
  32. FDA Roundup: March 25, 2022 . U.S. Food and Drug Administration (FDA) . 25 March 2022 . 25 March 2022 . 25 March 2022 . https://web.archive.org/web/20220325212932/https://www.fda.gov/news-events/press-announcements/fda-roundup-march-25-2022 . live .
  33. Web site: FDA updates Sotrovimab emergency use authorization . U.S. Food and Drug Administration (FDA) . 8 April 2022 . 5 April 2022 . 28 March 2022 . https://web.archive.org/web/20220328010007/https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-sotrovimab-emergency-use-authorization . live .
  34. FDA Roundup: April 5, 2022 . U.S. Food and Drug Administration . 5 April 2022 . 8 April 2022 . 8 April 2022 . https://web.archive.org/web/20220408000524/https://www.fda.gov/news-events/press-announcements/fda-roundup-april-5-2022 . live .
  35. Rockett R, Basile K, Maddocks S, Fong W, Agius JE, Johnson-Mackinnon J, Arnott A, Chandra S, Gall M, Draper J, Martinez E, Sim EM, Lee C, Ngo C, Ramsperger M, Ginn AN, Wang Q, Fennell M, Ko D, Lim HL, Gilroy N, O'Sullivan MV, Chen SC, Kok J, Dwyer DE, Sintchenko V . Resistance Mutations in SARS-CoV-2 Delta Variant after Sotrovimab Use . The New England Journal of Medicine . 386 . 15 . 1477–1479 . April 2022 . 35263515 . 8929376 . 10.1056/nejmc2120219 . letter . doi . free .

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