Sotrovimab

Last updated

Sotrovimab
Monoclonal antibody
Type Whole antibody
Source Human
Target Spike protein of SARS-CoV-2
Clinical data
Trade names Xevudy
Other namesVIR-7831, GSK4182136
AHFS/Drugs.com Multum Consumer Information
License data
Pregnancy
category
Routes of
administration
Intravenous
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only) [1] [3] [4]
  • US:Unapproved; Emergency Use Authorization [5]
Identifiers
CAS Number
  • 2423014-07-5
IUPHAR/BPS
DrugBank
UNII
KEGG

Sotrovimab, sold under the brand name Xevudy, is an investigational human neutralizing dual-action monoclonal antibody with activity against severe acute respiratory syndrome coronavirus 2, known as SARS-CoV-2. [6] [7] It is under development by GlaxoSmithKline and Vir Biotechnology, Inc. [6] [8] Sotrovimab is designed to attach to the spike protein of SARS-CoV-2. [6] [7] [9]

Contents

Development and mechanism of action

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). [10] [11] 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. [12] 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. [12] This epitope does not overlap with mutations observed in current SARS-Cov-2 variants of concern [11] 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). [11]

Sotrovimab has been engineered to possess an Fc LS mutation (M428L/N434S) that confers enhanced binding to the neonatal Fc receptor [13] resulting in an extended half-life and potentially enhanced drug distribution to the lungs. [14]

Sotrovimab has demonstrated activity via two antiviral mechanisms in vitro, antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). [14]

Research

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

Clinical pharmacology

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

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 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. [15] The study is ongoing and preliminary results have been published in the New England Journal of Medicine. [16]

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. [15] 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. [17] [18] [19] [20]

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. [21]

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References

  1. 1 2 "Xevudy". Therapeutic Goods Administration (TGA). 20 August 2021. Retrieved 17 September 2021.
  2. "New ATC 5th levels". WHOCC.
  3. 1 2 "TGA provisionally approves GlaxoSmithKline's COVID-19 treatment: sotrovimab (Xevudy)". Therapeutic Goods Administration (TGA) (Press release). 20 August 2021. Retrieved 4 September 2021.
  4. "COVID-19 treatment: GlaxoSmithKline Australia Pty Ltd, sotrovimab (Xevudy)". Therapeutic Goods Administration (TGA). 20 August 2021. Retrieved 22 October 2021.
  5. "Sotrovimab injection, solution, concentrate". DailyMed. Retrieved 15 June 2021.
  6. 1 2 3 "EMA starts rolling review of sotrovimab (VIR-7831) for COVID-19". European Medicines Agency (EMA) (Press release). 7 May 2021. Retrieved 21 May 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  7. 1 2 "EMA issues advice on use of sotrovimab (VIR-7831) for treating COVID-19". European Medicines Agency (EMA) (Press release). 21 May 2021. Retrieved 21 May 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  8. "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. Retrieved 21 May 2021.
  9. "EMA starts review of VIR-7831 for treating patients with COVID-19". European Medicines Agency (EMA) (Press release). 15 April 2021. Retrieved 21 May 2021.
  10. 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.
  11. 1 2 3 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.
  12. 1 2 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.
  13. 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.
  14. 1 2 3 4 "Assessment Report: Use of sotrovimab for the treatment of COVID-19" (PDF). European Medicines Agency. May 2021.
  15. 1 2 "EMA issues advice on use of sotrovimab (VIR-7831) for treating COVID-19". European Medicines Agency. May 2021.
  16. 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 . Retrieved 28 November 2021.
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  18. "Emergency Use Authorization 100: Sotrovimab". U.S. Food and Drug Administration (FDA). 28 May 2021.
  19. "Fact Sheet for Healthcare Providers Emergency Use Authorization (Eua) of Sotrovimab". U.S. Food and Drug Administration (FDA). 2021.
  20. "Frequently Asked Questions on the Emergency Use Authorization of Sotrovimab". U.S. Food and Drug Administration (FDA). 26 May 2021.
  21. "UK approves another antibody treatment for Covid". BBC News. 2 December 2021. Retrieved 2 December 2021.