VIR-7831 Antibody Description
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-7831 is a dual-action monoclonal antibody that was selected for clinical development based on its potential to both block viral entry into healthy cells and clear infected cells, as well as its potential to provide a high barrier to resistance.
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 VIR-7831 due to their collaboration to research and develop solutions for coronaviruses, including SARS-CoV-2.
VIR-7831 Antibody History
In April 2020, Vir and GSK entered into a collaboration to research and develop 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.
The companies will leverage GSK’s expertise in functional genomics and combine their CRISPR screening capabilities and artificial intelligence to identify anti-coronavirus compounds that target cellular host genes. They will also apply their combined expertise to research SARS-CoV-2 and other coronavirus vaccines.
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.”
The VIR - GSK sub-study also receives funding support through Operation Warp Speed, the U.S. government’s multi-agency effort to develop, manufacture, and distribute medical countermeasures for COVID-19.
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.
VIR-7831 Antibody Indication
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 approved by the U.S. FDA or any other regulatory authority. VIR-7831 is also evaluated in the global Phase 2/3 COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial - Intent to Care Early) trial.
No pediatric or pregnancy efficacy has been disclosed.
VIR-7831 Antibody News
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 (NTD). The study findings, together with data on immune evasion by mutations elsewhere in the spike protein published by scientists in Cell, 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 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.
VIR-7831 Clinical Trials
The Company announced on November 10, 2020; it plans to initiate two additional Phase 3 trials in the COMET clinical development program for VIR-7831:
Clinical Trial NCT04545060: A Randomized, Multi-center, Double-blind, Placebo-controlled Study to Assess the Safety and Efficacy of Monoclonal Antibody VIR-7831 for the Early Treatment of Coronavirus Disease 2019 (COVID-19) in Non-hospitalized Patients. Last Update Posted: January 7, 2021. This is a phase 2/3 study in which subjects with coronavirus disease 2019 (COVID-19) will receive VIR-7831 or placebo and be assessed for safety, tolerability, efficacy, and pharmacokinetics.
Clinical Trial NCT04634409: A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of Mono and Combination Therapy With Monoclonal Antibodies in Participants With Mild to Moderate COVID-19 Illness (BLAZE-4).
Last Update Posted: January 22, 2021.