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Sotrovimab (VIR-7831) Antibody

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May 30, 2021
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Sotrovimab (VIR-7831) Antibody Description

Sotrovimab (VIR-7831) (GSK4182136) is a fully human anti-SARS-CoV-2 monoclonal antibody selected based on its potential to neutralize the virus in vitro, kill infected cells, provide a high barrier to resistance, and achieve high concentrations in the lungs (one of the major sites of infection).

Vir Biotechnology's antibody binds to an epitope on SARS-CoV-2 shared with SARS-CoV-1 (SARS). In pre-clinical trials, the antibody has shown the ability to neutralize the SARS-CoV-2 live virus by binding to an epitope on SARS-CoV-2 shared with SARS-CoV-1, indicating that the epitope is highly conserved, which may make it more difficult for escape mutants to develop.

Vir and GSK are advancing Sotrovimab (VIR-7831) due to their collaboration to research and develop solutions for coronaviruses, including SARS-CoV-2.

The U.S. Food and Drug Administration issued an emergency use authorization on May 26, 2021, for the investigational monoclonal antibody therapy Sotrovimab for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kilograms [about 88 pounds]) 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.

This FDA's EUA allows for Sotrovimab to be distributed and administered as a 500-milligram single dose intravenously by health care providers.

Sotrovimab (VIR-7831) Antibody History

In April 2020, Vir and GSK announced a collaboration to research and developed solutions for coronaviruses, including SARS-CoV-2, the virus that causes COVID-19. The collaboration uses Vir’s proprietary monoclonal antibody platform technology to accelerate existing and identify new anti-viral antibodies that could be used as therapeutic or preventive options to help address the current COVID-19 pandemic and future outbreaks.

A phase 2/3 clinical study was launched on September 10, 2020, in which subjects with coronavirus disease 2019 (COVID-19) will receive VIR-7831 or placebo and be assessed for safety, tolerability, efficacy, and pharmacokinetics. Initial Phase 3 results may be available as early as the end of 2020; results for the primary endpoint are expected in the first quarter of 2021, with current estimates at January 2021.

A manuscript developed by Vir in collaboration with the MRC-University of Glasgow Centre for Virus Research, published on November 5, 2020, "shows that the receptor-binding motif of SARS-CoV-2, a major target of neutralizing antibodies, is evolving at a higher rate than the rest of the receptor-binding domain and spike, and is resilient to change,” said Herbert “Skip” Virgin, M.D., Ph.D., chief scientific officer of Vir, in a press release. 

“It is reminiscent of our experience with influenza A, where the mutability of the region targeted by the most potent neutralizing antibodies results in ineffective immunity year-over-year. Our demonstration of a virulent SARS-CoV-2 immune evasion mutant provides a cautionary tale for how we address this pandemic. It indicates the importance of ongoing surveillance for immune evasion mutations in the development of antibodies and vaccines.”

On December 17, 2020, the U.S. NIH stated, 'One sub-study evaluates VIR-7831. Antibodies are infection-fighting proteins naturally made by the immune system. Antibodies can prevent viruses from infecting cells, sometimes binding to the viruses' surface. Synthetic versions of these antibodies, prepared in a laboratory, are known as monoclonal antibodies.'

George Scangos, Ph.D., CEO at Vir, stated in a press release issued on January 27, 2021,  “We believe that VIR-7831 has significant potential as a single agent, and we are optimistic about the pending interim data from two Phase 3 trials evaluating its potential for early treatment and in hospitalized patients. As the virus continues to evolve, we, along with Lilly and GSK, share the view that we should pursue all possibilities to help end the pandemic and maximize the number of lives that can be saved. This trial is a first step to assess whether the administration of VIR-7831, with its high barrier to resistance and potent effector function, alongside bamlanivimab, which has strong outcomes data in early treatment, can provide potential benefits beyond monotherapy.”

On March 3, 2021, the companies were informed that while VIR-7831 met initial pre-specified criteria to continue to the next phase of the ACTIV-3 trial and there were no reported safety signals, sensitivity analyses were available data raised concerns about the magnitude of potential benefit. The independent Data and Safety Monitoring Board (DSMB) has recommended that the VIR-7831 arm of the trial be closed to enrollment while the data mature. George Scangos stated in a related press release, “While we are disappointed with the recommendation of the DSMB, we are encouraged by the safety profile of VIR-7831 and by the possibility of a benefit on top of remdesivir and corticosteroids in this advanced cohort of patients."

On March 10, 2021, George Scangos, Ph.D., chief executive officer of Vir, commented in a press release, "The dual-action design of VIR-7831 to both block viral entry into healthy cells and clear infected cells, as well as its high barrier to resistance, are key distinguishing characteristics. These findings, paired with our pending publication of resistance data, demonstrate the potential of VIR-7831 to prevent the most severe consequences of COVID-19 and highlight its potential ability to protect against the currently circulating strains of the coronavirus.”

George Scangos, Ph.D., CEO of Vir, said in a press statement issued on March 29, 2021, “This virologic evaluation of two antibodies with distinct resistance profiles is an encouraging advance in our fight against the pandemic. VIR-7831 demonstrated positive results in the COMET-ICE trial, and recent pre-clinical data suggest that VIR-7831 maintains activity against current circulating variants of concern. Now, with these exciting new data from the BLAZE-4 trial, we believe that VIR-7831 has an important role to play as both monotherapies and in combination with other mAbs. We look forward to continuing conversations with the FDA about VIR-7831 as monotherapy and co-administered with bamlanivimab.”

On May 29, the United Arab Emirates Ministry of Health and Prevention approved the emergency use of Sotrovimab, becoming the first country in the world to both license and enable immediate patient use.

VIR Bio is a California-based clinical-stage immunology company that combines immunologic insights with cutting-edge technologies to treat and prevent serious infectious diseases. 'We engineer the fully human antibodies that we discover to enhance their therapeutic potential,' says the company's website

The VIR - GSK study received funding support through Operation Warp Speed, the U.S. government’s multi-agency effort to develop, manufacture, and distribute medical countermeasures for COVID-19.

Sotrovimab (VIR-7831) Antibody Indication

Sotrovimab (VIR-7831) is being evaluated for the early treatment of COVID-19, a disease caused by the SARS-CoV-2 virus in patients at high risk of hospitalization. VIR-7831 is an investigational compound not Authorized by the U.S. FDA.

Sotrovimab VIR-7831 is also evaluated in the global Phase 2/3 COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial - Intent to Care Early) trial.

Sotrovimab (VIR-7831) Antibody News

May 29, 2021 - The United Arab Emirates Ministry of Health and Prevention (MoHAP) announced the emergency use Approval of the GSK, "Sotrovimab (Vir-7831)" treatment that offers the prospect of reducing hospitalization for more than 24 hours and fatalities by as much as 85% when administered to patients as an early treatment for COVID-19.

May 26, 2021 - The U.S. FDA issued a EUA for the investigational monoclonal antibody therapy sotrovimab to treat mild-to-moderate COVID-19 in adults and pediatric patients. George Scangos, Ph.D., CEO of Vir, said: “Our distinctive scientific approach has led to a single monoclonal antibody that, based on an interim analysis, resulted in an 85% reduction in all-cause hospitalizations or death, and has demonstrated, in vitro, that it retains activity against all known variants of concern, including the emerging variant from India. I believe that sotrovimab is a critical new treatment option in the fight against the current pandemic and potentially future coronavirus outbreaks. At Vir, our aim is not only to deliver a clinically effective therapy for COVID-19 but also to provide effective therapy against SARS-CoV-2 variants and potential pandemics of tomorrow.”

May 7, 2021 - The European Medicine Agency (EMA) human medicines committee confirmed it had started a ‘rolling review’ of data on sotrovimab (also known as VIR-7831 and GSK4182136), a monoclonal antibody developed by GlaxoSmithKline and Vir Biotechnology, Inc. for the treatment of COVID-19. The decision to start the rolling review is based on preliminary results from an ongoing study looking at the ability of the medicine to prevent hospitalization or death in non-hospitalized patients with COVID-19. However, EMA has not yet received the full dataset, and it is too early to draw any conclusions regarding the benefit-risk balance of the medicine.

May 7, 2021 - Vir Bio confirmed Sotrovimab, along with VIR-7832, is evaluated in Phase 1b/2a National Health Service-supported AGILE trial in adults with mild to moderate COVID-19. VIR-7832 is the second monoclonal antibody from the Vir-GSK collaboration to be investigated as a potential COVID-19 treatment.

April 15, 2021 - GlaxoSmithKline plc and Vir Biotechnology, Inc. (Nasdaq: VIR) announced that the European Medicines Agency had started a review of VIR-7831 (GSK4182136), an investigational dual-action SARS-CoV-2 monoclonal antibody, for the treatment of adults and adolescents (aged 12 years and over and weighing at least 40 kg) with COVID-19 who do not require oxygen supplementation and who are at high risk of progressing to severe COVID-19.

April 14, 2021 - Australia's Therapeutic Goods Administration (TGA) has granted a provisional determination to GlaxoSmithKline Australia Pty Ltd (GSK) in relation to the monoclonal antibody treatment SOTROVIMAB (GSK4182136). The granting of a provisional determination means that the TGA has decided that GSK is now eligible to apply for provisional registration for the Australian Register of Therapeutic Goods treatment.

April 8, 2021 - Vir Biotechnology, Inc. announced new preclinical research highlighting novel mechanisms by which the SARS-CoV-2 virus enters host cells and identifying how auxiliary receptors may impact the clinical efficacy of monoclonal antibodies (mAbs). The research highlights the distinct mechanism of action of a non-receptor-binding motif (RBM)-targeting antibodies, such as VIR-7831 and VIR-7832, the Company’s investigational SARS-CoV-2 mAbs that target a conserved non-RBM site within the receptor-binding domain.

April 5, 2021 - Vir Biotechnology, Inc. today announced new preclinical research demonstrating the ability of VIR-7831, the company’s investigational SARS-CoV-2 virus monoclonal antibody (mAb), to maintain its neutralizing activity against a mutation in the receptor-binding domain (RBD) of SARS-CoV-2, called L452R, which is found in the California variant (B.1.427/B.1.429). Study results also demonstrate that the L452R mutation reduced the neutralization potency of plasma from vaccinated and convalescent donors and the neutralization activity of 14 RBD-specific and 10 N-terminal domain (NTD)-specific monoclonal antibodies, including three clinical-stage mAbs.

April 1, 2021 - A non-peer-reviewed study, 'SARS-CoV-2 immune evasion by variant B.1.427/B.1.429', was published. In this new study, researchers at Vir and the University of Washington report the rapid and exponentially increasing spread of the California variant throughout all 50 states and 29 additional countries worldwide and characterize the impact of its three mutations: S13I and W152C in the NTD and L452R in the RBD.

March 29, 2021 - Vir Biotechnology, Inc., Eli Lilly and Company, and GSK plc announced topline data from the expanded Phase 2 BLAZE-4 trial studying low-risk adult patients with mild to moderate COVID-19. Results showed that investigational bamlanivimab (LY-CoV555) 700 mg co-administered with VIR-7831 (also known as GSK4182136) 500 mg demonstrated a 70 percent (p<0.001) relative reduction in persistently high viral load (> 5.27; cycle threshold value < 27.5) at day 7 compared to placebo, meeting the primary endpoint. Also, bamlanivimab administered with VIR-7831 demonstrated a statistically significant reduction compared to placebo in the key virologic secondary endpoints of mean change from baseline to days 3, 5, and 7 SARS-CoV-2 viral load.

March 26, 2021 - GlaxoSmithKline plc and Vir Biotechnology, Inc. announced the submission of an application to the U.S. Food and Drug Administration requesting Emergency Use Authorization for VIR-7831 (GSK4182136), an investigational dual-action SARS-CoV-2 monoclonal antibody for the treatment of adults and adolescents (aged 12 years and older weighing at least 40 kg) with mild-to-moderate COVID-19 who are at risk for progression to hospitalization or death. GSK and Vir will continue discussions with the European Medicines Agency and other global regulators to make VIR-7831 available to patients with COVID-19 as soon as possible. 

March 10, 2021 - Vir Biotechnology, Inc. and GlaxoSmithKline plc (LSE/NYSE: GSK) announced that an Independent Data Monitoring Committee (IDMC) recommended that the Phase 3 COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial - Intent to Care Early) trial evaluating VIR-7831 (GSK4182136) as monotherapy for the early treatment of COVID-19 in adults at high risk of hospitalization be stopped for enrollment due to evidence of profound efficacy. The IDMC recommendation was based on an interim analysis of data from 583 patients enrolled in the COMET-ICE trial, which demonstrated an 85% reduction in hospitalization or death in patients receiving VIR-7831 as monotherapy placebo the primary endpoint of the trial. Based on these results, Vir and GSK plan to submit an Emergency Use Authorization application to the U.S. Food and Drug Administration (FDA) and authorizations in other countries. Data from this registrational trial will also form the basis for a Biologics License Application submission to the FDA.

March 3, 2021 - Vir Biotechnology, Inc. and GlaxoSmithKline plc announced an update on the VIR-7831 (GSK4182136) arm of the National Institutes of Health’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Program Phase 3 clinical trial. The companies were informed that while VIR-7831 met initial pre-specified criteria to continue to the next phase of the ACTIV-3 trial and there were no reported safety signals, sensitivity analyses of the available data raised concerns about the magnitude of potential benefit. The independent Data and Safety Monitoring Board (DSMB) has recommended that the VIR-7831 arm of the trial be closed to enrollment while the data mature. The DSMB recommendation was based on a routine, pre-planned safety and efficacy data review of the first 300 patients hospitalized with COVID-19 enrolled in ACTIV-3. The companies stated they 'will continue discussions with the NIH about appropriate ways to further assess the potential of VIR-7831 in the hospitalized population as all parties gain a fuller understanding of the still-emerging data.'

February 17, 2021 - GlaxoSmithKline plc and Vir Biotechnology, Inc. announced they had signed a binding agreement to expand their existing collaboration to include the research and development of new therapies for influenza and other respiratory viruses. The expanded collaboration builds on the agreement signed in 2020 to research and develop therapies for coronaviruses.

February 1, 2021 - Vir Biotechnology, Inc. announced the publication of new research characterizing a novel site of vulnerability on the SARS-CoV-2 spike protein – specifically the N-terminal domain. Together with data on immune evasion by mutations elsewhere in the spike protein published by scientists in Cell, the study findings begin to paint a comprehensive picture of the mechanisms that SARS-CoV-2 may utilize to evade immunity. These data collectively indicate the importance of carefully targeting conserved regions of the spike for vaccines and clinical monoclonal antibodies.

January 27, 2021 - Eli Lilly and Company, Vir Biotechnology, Inc., and GlaxoSmithKline plc announced a collaboration to evaluate a combination of two COVID-19 therapies in low-risk patients with mild to moderate COVID-19. Lilly has expanded its ongoing BLAZE-4 trial to evaluate the administration of bamlanivimab (LY-CoV555) 700mg with VIR-7831 (also known as GSK4182136) 500mg, two neutralizing antibodies that bind to different epitopes of the SARS-CoV-2 spike protein. This unique collaboration marks the first time that monoclonal antibodies from separate companies will be brought together to explore potential outcomes.

January 12, 2021 - Vir Biotechnology, Inc. and GlaxoSmithKline plc announced an agreement with the U.K.-based AGILE initiative to evaluate VIR-7832 in patients with mild to moderate COVID-19 in Phase 1b/2a clinical trial. VIR-7832 is a different neutralizing COVID-19 antibody that preclinical data suggests has two distinguishing properties: an enhanced ability to clear infected cells and the potential to enhance virus-specific T-cell function, which could help treat and/or prevent COVID-19 infection. This is the second monoclonal antibody from the Vir-GSK collaboration to be investigated as a potential COVID-19 treatment.

December 17, 2020 - Vir Biotechnology, Inc. and GlaxoSmithKline plc announced that the first patient had been dosed in a new sub-trial of the National Institutes of Health’s Accelerating COVID-19 Therapeutic Interventions and Vaccines Program Phase 3 clinical trial. This trial is designed to evaluate the safety and efficacy of VIR-7831 for the treatment of hospitalized adults with COVID-19.

November 10, 2020 - George Scangos, Ph.D., chief executive officer of Vir Bio, said in a press release: “We expect to share initial results from the trial as early as January and look forward to advancing VIR-7831 into new patient populations alongside the initiation of Phase 1b/2a trial for our second investigational SARS-CoV-2 neutralizing antibody, VIR-7832."

November 6, 2020 - California based Vir Biotechnology, Inc. announced the publication of new research demonstrating that the immunodominant SARS-CoV-2 receptor binding motif (RBM) is the least conserved region in the SARS-CoV-2 spike protein, allowing for the occurrence of mutations without disrupting human ACE2 (hACE2) binding, which mediates viral entry. Researchers also characterize the virulence and fitness of N439K, a prevalent variant in the RBM that demonstrated resistance to human neutralizing monoclonal antibodies (mAbs), including one that is currently being evaluated in clinical trials.

October 8, 2020 - Study published by Nature: Fc-optimized antibodies elicit CD8 immunity to viral respiratory infection.

October 6, 2020 - Vir Biotechnology and GSK announce the global expansion to Phase 3 of COMET-ICE study evaluating VIR-7831 to treat COVID-19. VIR-7831 (also known as GSK4182136) is a fully human anti-SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus-2) monoclonal antibody that was selected based on its potential to neutralize the virus, kill infected cells, provide a high barrier to resistance, and achieve high concentrations in the lungs (one of the major sites of infection). Following a positive assessment of unblinded safety data from the lead-in portion of the trial by an Independent Data Monitoring Committee on September 30, 2020, the COMET-ICE registrational study will expand globally to additional North American sites in South America and Europe.

September 24, 2020 - RESEARCH ARTICLE: Ultrapotent human antibodies protect against the SARS-CoV-2 challenge via multiple mechanisms.

September 16, 2020 - Study published by Cell: Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology.

August 31, 2020 - Vir Biotechnology, Inc. and GlaxoSmithKline plc announced that the first patient was dosed last week in a phase 2/3 study with VIR-7831 (also known as GSK4182136), a fully human anti-SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus-2) monoclonal antibody, for the early treatment of COVID-19 in patients who are at high risk of hospitalization.

May 18, 2020 - Study published in Nature: Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody.

April 21, 2020 - Study: Developing therapeutic monoclonal antibodies at a pandemic pace.

Sotrovimab (VIR-7831) Antibody Clinical Trials

The Company announced on May 7, 2021, it plans to initiate two additional Phase 3 trials in the COMET clinical development program for VIR-7831.  These Phase 3 programs include COMET-TAIL: A Phase 3 trial expected to begin in the second quarter of 2021 as an early treatment in high-risk adults to assess whether IM-administered sotrovimab can reduce hospitalization or death due to COVID-19; and COMET-STAR: A Phase 3 trial expected to begin in the second quarter of 2021 in uninfected adults at high risk to determine whether IM-administered sotrovimab can prevent symptomatic infection.