30 March 2021 - - US-based pharmaceutical company Eli Lilly and Company (NYSE: LLY), US-based Vir biotechnology, Inc. (NASDAQ: VIR) and UK-based pharmaceutical company GlaxoSmithKline plc (LSE: GSK) (NYSE: GSK) have released topline data from the expanded Phase 2 BLAZE-4 trial studying low-risk adult patients with mild to moderate COVID-19, the companies said.

Results showed that investigational bamlanivimab (LY-CoV555) 700 mg co-administered with VIR-7831 (also known as GSK4182136) 500 mg demonstrated a 70 % (p 5.27; cycle threshold value < 27.5) at day 7 compared to placebo, meeting the primary endpoint.

In addition, 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 in SARS-CoV-2 viral load.

There were no events for the secondary endpoint of COVID-19 related hospitalization or death by day 29 in either study arm.

One patient (in the treatment arm) visited the emergency room for COVID-19 related symptoms. No serious adverse events were seen with co-administration of bamlanivimab and VIR-7831.

Bamlanivimab and VIR-7831 bind to different regions of the spike protein of SARS-CoV-2. Preclinical data suggest the administration of these two investigational antibodies together may provide protection against current variants of SARS-CoV-2 that are resistant to bamlanivimab.

VIR-7831 is an investigational compound, not approved by the US Food and Drug Administration or any other regulatory authority.

An Emergency Use Authorization application for VIR-7831 has been submitted to the FDA, based on the results of the COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial - Intent to Care Early) trial, which stopped enrollment early based on data from an interim analysis demonstrating an 85% reduction in hospitalisation or death in patients receiving VIR-7831 as monotherapy compared to placebo, the primary endpoint of the trial.

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.

The three companies anticipate engaging with global regulators, including the FDA, regarding the possible co-administration of bamlanivimab and VIR-7831 for the treatment of COVID-19.

Bamlanivimab has not been approved by the FDA for any use. It is not known if bamlanivimab is safe and effective for the treatment of COVID-19.

Bamlanivimab is authorized under an Emergency Use Authorization only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of bamlanivimab under Section 564(b) (1) of the Act, 21 USC § 360bbb-3(b) (1), unless the authorization is terminated or revoked sooner.

COMET-ICE is a multi-center, double-blind, placebo-controlled Phase 3 trial evaluating VIR-7831 in adults with mild or moderate COVID-19 at high risk of progression to severe disease.

The trial was stopped for enrollment on March 10, 2021, based on an interim analysis, which demonstrated an 85% (p=0.002) reduction in hospitalization or death in those receiving VIR-7831 compared to placebo.

Bamlanivimab is a recombinant, neutralizing human IgG1 monoclonal antibody directed against the spike protein of SARS-CoV-2. It is designed to block viral attachment and entry into human cells, thus neutralizing the virus, potentially treating COVID-19.

Bamlanivimab emerged from the collaboration between Lilly and AbCellera to create antibody therapies for the prevention and treatment of COVID-19.

Lilly scientists rapidly developed the antibody in less than three months after it was discovered by AbCellera and the scientists at the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center. It was identified from a blood sample taken from one of the first US patients who recovered from COVID-19.

Lilly has successfully completed a Phase 1 study of bamlanivimab in hospitalized patients with COVID-19 (NCT04411628). 

A Phase 2/3 study in people recently diagnosed with COVID-19 in the ambulatory setting (BLAZE-1, NCT04427501) is ongoing. A Phase 3 study of bamlanivimab for the prevention of COVID-19 in residents and staff at long-term care facilities (BLAZE-2, NCT04497987) is ongoing. In addition, bamlanivimab is being tested in the National Institutes of Health-led ACTIV-2 study in ambulatory COVID-19 patients.

Bamlanivimab is authorized in the US for the treatment of mild to moderate COVID-19 in adults and pediatric patients 12 years and older with a positive COVID-19 test, who are at high risk for progressing to severe COVID-19 and/or hospitalization. Bamlanivimab should be administered as soon as possible after a positive COVID-19 test and within 10 days of symptom onset.

VIR-7831 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 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-7831, which incorporates Xencor's Xtend technology, also 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.

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 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.