British multinational pharmaceutical company GlaxoSmithKline (GSK) and California’s Vir Biotechnology reported recently that the jointly developed antibody treatment can reduce COVID-19 deaths and hospitalizations. Recent data from a Phase 3 clinical trial reveals that their investigational product known as VIR-7831, a monoclonal antibody, had an 85% efficacy in reducing hospitalization or death from COVID-19 compared to a placebo. The two ventures, highly confident based on the recent data, declared that the investigational product’s “profound efficacy” suggests that the drug has enormous potential to reduce disease progression, thus helping to slow down hospitalizations associated with COVID-19. The companies are seeking emergency use authorization and also announced the results of a new study revealing efficacy of the product against variants, such as those from the UK, South Africa, and Brazil.
During the Phase 3 COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial – Intent to Care Early) clinical trial, the Independent Data Monitoring Committee recommended that the study cease, given the 85% reduction in hospitalization or death. Because of these results, the two companies declared in a recent press release that they would be seeking Emergency Use Authorization (EUA) in the U.S. and in other nations. The company’s other study reveals that VIR-7831 maintains activity against new circulating COVID-19 variants.
TrialSite provides a breakdown of this recent news.
Why did the Independent Data Monitoring Committee (IDMC) recommend the Phase 3 COMET-ICE study?
Because they looked at the study data and found that the drug appears to be working—that is based on evidence of profound efficacy.
Are these the final study results and are they peer reviewed?
No. These are interim analyses and the data has not been peer reviewed.
What are the interim study results?
Based on the interim analysis of data from 583 patients enrolled in the COMET-ICE trial, which demonstrated an 85% (p=0.002) reduction in hospitalization or death in patients receiving VIR-7831 as monotherapy compared to placebo, the primary endpoint of the trial. VIR-7831 was well tolerated. As the trial remains ongoing and blinded with patients continuing to be followed for 24 weeks, additional results, including epidemiology and virology data, will be forthcoming once the trial is completed.
Will the sponsors submit an EUA application to the U.S. Food and Drug Administration (FDA) as well as a Biologics License Application (BLA)?
Yes. The company plans on doing so. They will first go for the EUA more than likely.
What does their other study show about the investigational product’s efficacy against the SARS-CoV-2 variants?
Pending online publication in bioRxiv, the new data demonstrates that VIR-7831 maintains activity against the current circulating variants of concern including the UK, South African and Brazilian variants based on in vitro data from pseudotyped virus assays.
What makes VIR-7831 so promising?
This monoclonal antibody was designed with a dual-action in mind allowing the investigational product to not only block viral entry into healthy cells but also clear these infected cells. Moreover, its high barrier resistance make the therapy candidate attractive.
How is VIR-7831 different from the other monoclonal antibodies, such as those from Lilly and Regeneron, for example?
According to GSK and Vir’s press release, VIR-7831 binds to a highly conserved epitope of the spike protein, which may make it more difficult for resistance to develop.
What does the entire COMET clinical development program for VIR-7831 look like?
COMET-PEAK: An ongoing Phase 2 trial with two parts: to compare the safety and viral kinetics of 500 mg intramuscularly (IM) administered VIR-7831 to 500 mg intravenously administered VIR-7831 among low-risk adults with mild to moderate COVID-19 and to evaluate the similarity and pharmacokinetics between VIR-7831 manufactured by different processes.
COMET-TAIL: A Phase 3 trial expected to begin in the second quarter of 2021 in high-risk adults to assess whether IM-administered VIR-7831 can reduce hospitalization or death due to COVID-19.
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 VIR-7831 can prevent symptomatic infection.
What are the details of this pivotal Phase 3 COMET-ICE trial?
The Phase 3 portion of the COMET-ICE trial assessed the safety and efficacy of a single intravenous infusion of VIR-7831 (500 mg) or placebo in non-hospitalized participants globally, and this interim analysis included 291 patients in the treatment arm and 292 patients in the placebo arm. The primary efficacy endpoint is the proportion of patients who have progression of COVID-19 as defined by the need for hospitalization for at least 24 hours or death within 29 days of randomization. Among those studied, 63% were Hispanic or Latinx and 7% were Black or African American. According to the Centers for Disease Control and Prevention these populations are approximately three times more likely to be hospitalized and approximately two times more likely to die from COVID-19.
In what other programs is VIR-7831 under study?
VIR-7831 is also being evaluated in the outpatient setting in BLAZE-4, a Phase 2 trial sponsored by Eli Lilly and Company, designed to assess the safety and efficacy of Eli Lilly’s bamlanivimab (LY-CoV555) alone and bamlanivimab with other neutralizing antibodies, including VIR-7831, versus placebo in low-risk adults with mild to moderate COVID-19.
Additionally, VIR-7831, along with VIR-7832, will be evaluated in the 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. Again both VIR-7831 and VIR-7832 are investigational compounds, not approved by the U.S. Food and Drug Administration or any other regulatory authority.
What was the COMET-ICE clinical trial design?
The multicenter, double-blind, placebo-controlled COMET-ICE trial is investigating VIR-7831 in adults with mild or moderate COVID-19 who are at high risk of progression to severe disease. The Phase 1 lead-in portion of the trial, which served as the first-in-human assessment, evaluated the safety and tolerability of a single 500 mg intravenous (IV) infusion of VIR-7831 or placebo over a 14-day period in 21 non-hospitalized adults enrolled across the United States.
In October 2020, based on a positive evaluation of safety and tolerability data of VIR-7831 from the lead-in part of the trial by an Independent Data Monitoring Committee, the trial began enrolling patients in North America and additional sites in South America and Europe in the global Phase 3 portion of the trial. This part of the trial is assessing the safety and efficacy of a single IV infusion of VIR-7831 or placebo in up to 1,300 non-hospitalized participants globally.
About VIR-7832 / GSK4182137
VIR-7832 is an investigational dual-action SARS-CoV-2 monoclonal antibody. Preclinical data suggest it has the potential to both block viral entry into healthy cells and an enhanced ability to clear infected cells. The antibody binds to an epitope on SARS-CoV-2 that is shared with SARS-CoV-1 (the virus that causes SARS), indicating that the epitope is highly conserved, which may make it more difficult for resistance to develop. VIR-7832, which incorporates Xencor’s Xtend and other Fc technologies, has been designed to achieve high concentration in the lungs to ensure optimal penetration into airway tissues affected by SARS-CoV-2 and to have an extended half-life. Importantly, VIR-7832 also has been engineered to potentially enhance virus-specific T cell function, which could help treat and/or prevent COVID-19 infection.
About the Vir and GSK Collaboration
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 antiviral 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 capabilities in CRISPR screening 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.