Vir Biotechnology, Inc and GlaxoSmithKline plc provided an update on the VIR-7831 (GSK4182136) arm of the National Institutes of Health’s (NIH) 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 companies 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.
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.
George Scangos, Ph.D., chief executive officer of Vir, said: “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. We want to thank NIH for their work to assess the benefits of VIR-7831 and other agents, and look forward to working with them to further understand the potential of VIR-7831 to provide a benefit in this population. In addition, we are eagerly anticipating the upcoming data from the Phase 3 COMET-ICE trial in newly-diagnosed COVID-19 patients at high risk of hospitalization.”
Christopher Corsico, Senior Vice President Development, GSK, said: “We want to thank the patients who participated in this study and the NIH for investing in the ACTIV trial to evaluate the four monoclonal antibodies, as it recognizes the need for differentiated treatments, especially as new variants emerge globally. These and other anticipated data will provide valuable insights about how VIR-7831 can contribute to the fight against this pandemic.”
VIR-7831 is an investigational, dual-action monoclonal antibody that has been shown in preclinical trials to both block viral entry into healthy cells and clear infected cells, which may protect patients from disease progression.
The antibody has also shown the ability to neutralize the SARS-CoV-2 live virus by binding to a highly conserved epitope of the spike protein, which may make it more difficult for resistance to develop. So far, the variants of concern, including the UK, South African and Brazilian variants, do not overlap with the VIR-7831 targeted epitope of the virus, and, therefore, VIR and GSK believe that it should maintain full activity against these strains.
In addition to the ACTIV-3 trial, VIR-7831 is also being evaluated in the outpatient setting in the following clinical trials:
- COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial – Intent to Care Early): A Phase 3 trial to evaluate VIR-7831 for the early treatment of COVID-19 in adults at high risk of hospitalization or death.
- BLAZE-4 (sponsored by Eli Lilly and Company): A Phase 2 trial 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.