Lilly, GSK, and Vir Announce Bamlanivimab/VIR-7831 Dual-Antibody Cocktail Significantly Reduces Viral Load in Low-Risk COVID-19 Patients

March 29, 2021/BioonBIOON/--Eli Lilly(Lilly) and Vir Biotechnology, Inc.GlaxoSmithKline PLC.(GSK) recently jointly announced the top-line data from the expanded Phase 2 BLAZE-4 trial, which studied adult patients at low risk with mild to moderate COVID-19. The results showed that the trial met its primary endpoint: on Day 7 of treatment, combination therapy with 700 mg of bamlanivimab (LY-CoV555) and 500 mg of VIR-7831 (GSK4182136) reduced persistent high viral load (>5.27, cycle threshold [Ct value]) compared with placebo.<27.5) by 70% (p<0.001).

Furthermore, regarding the viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from baseline assessment to Day 3, Day 5, and Day 7BalanceIn terms of the key virologic secondary endpoint of mean change, the combination of bamlanivimab and VIR-7831 resulted in a statistically significant reduction in viral load compared with placebo. By Day 29, no COVID-19-related hospitalizations or deaths (secondary endpoints) occurred in either study group. During the study, one patient (in the treatment group) visited the emergency department due to COVID-19-related symptoms. No serious adverse events occurred with the combination of bamlanivimab and VIR-7831.Adverse Reactions。

Bamlanivimab and VIR-7831 are two monoclonal antibodies that bind to distinct regions of the SARS-CoV-2 spike protein. Preclinical data suggest that the concurrent use of these two antibodies may provide protection against SARS-CoV-2 variants currently resistant to bamlanivimab.

Based on the aforementioned data, the three companies plan to collaborate with partners including those in the United StatesFDAglobal regulatory authorities, including those in China, are consulting on the potential combined use of bamlanivimab and VIR-7831 for the treatment of COVID-19.

Daniel Skovronsky, M.D., Ph.D., Chief Scientific Officer of Eli Lilly and President of Eli Lilly Research Laboratories, stated, “Reduction in persistently high viral load is an important virologic endpoint, which inEli Lilly“confirmed in the Phase 2 BLAZE-1 trial and subsequently validated in Phase 3 trials, which closely correlated with clinical outcomes of hospitalization and death among high-risk patients with COVID-19. These virologic data support our belief that the combination of bamlanivimab and VIR-7831 may represent a promising therapeutic option for the treatment of COVID-19.”

Dr. George Scangos, CEO of Vir, stated, “The virological assessment of two antibodies with distinct resistance profiles represents an encouraging advancement in our fight against the COVID-19 pandemic. In the COMET-ICE trial, VIR-7831 demonstrated positive results, and recent preclinical data indicate that VIR-7831 remains active against currently circulating viral variants. With these exciting new data from the BLAZE-4 trial, we believe VIR-7831 plays a significant role both as monotherapy and in combination with other monoclonal antibodies. We look forward to collaborating withFDAContinue the discussion on VIR-7831 as monotherapy and in combination with bamlanivimab.”

GlaxoSmithKlineDr. Hal Barron, Chief Scientific Officer and President of Research and Development, stated, “These early data from the BLAZE-4 trial, together with the results from the COMET-ICE trial, demonstrate an 85% reduction in disease progression to hospitalization or death with VIR-7831, supporting our hypothesis that targeting highly conserved epitopes may enable VIR-7831 to deliver therapeutic benefits to patients. We are continuing to collaborate with regulatory authorities to advance VIR-7831 as a monotherapy, and potentially in combination with other monoclonal antibodies, for patients in need.”

VIR-7831 (GSK4182136, image source: pharmaintelligence.informa.com)

VIR-7831 is a dual-acting monoclonal antibody against the novel coronavirus (SARS-CoV-2). Preclinical data indicate that VIR-7831 has the potential to both block viral entry into healthy cells and clear infected cells. VIR-7831 binds to an epitope shared by SARS-CoV-2 and SARS-CoV-1 (the virus causing SARS), suggesting that this epitope is highly conserved, which may make the development of resistance more difficult. Incorporating Xencor’s Xtend technology, VIR-7831 is also designed to achieve high concentrations in the lungs to ensure optimal penetration into airway tissues affected by SARS-CoV-2, while offering an extended half-life.

Just recently, GlaxoSmithKline and Vir to the United StatesFDAAn application has been submitted requesting Emergency Use Authorization (EUA) for VIR-7831: 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 high risk for progression to hospitalization or death. The parties will continue discussions with the European Medicines Agency (EMA) and other global regulatory authorities to make VIR-7831 available to patients with COVID-19 as soon as possible.

FDAThe Emergency Use Authorization (EUA) submission is based on an interim analysis of efficacy and safety data from the Phase 3 COMET-ICE trial (COVID-19 Monoclonal Antibody Efficacy Trial – Intent to Care Early). This trial evaluated the efficacy of VIR-7831 as monotherapy for early treatment in adult patients with COVID-19 at high risk of hospitalization. The results of the interim analysis were based on data from 583 enrolled patients. The data demonstrated that the trial met its primary endpoint: compared with the placebo group, patients treated with VIR-7831 had an 85% reduction in hospitalization or death (p=0.002). Consequently, the Independent Data Monitoring Committee (IDMC) recommended stopping the trial due to evidence of significant efficacy.

Bamlanivimab (LY-CoV555) is a potent, neutralizing IgG1 monoclonal antibody targeting the SARS-CoV-2 spike protein. It was developed to block viral attachment and entry into human cells, thereby neutralizing the virus and potentially preventing and treating COVID-19. Bamlanivimab originated from a research collaboration between Eli Lilly and AbCellera to develop antibody therapies for the prevention and treatment of COVID-19. After its discovery by AbCellera and testing by scientists at the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center,Eli LillyScientists rapidly developed this antibody in less than three months, identifying it from a blood sample collected from one of the first COVID-19 patients to recover in the United States.

In February this year, the U.S. FDA granted Emergency Use Authorization (EUA) for the dual-antibody therapy consisting of 1400 mg etesevimab and 700 mg bamlanivimab. This therapy was authorized for the treatment of patients aged 12 years and older with mild to moderate COVID-19 who are at risk of progressing to severe COVID-19 and/or hospitalization. Patients should receive the single intravenous infusion of the etesevimab and bamlanivimab dual-antibody therapy as soon as possible after being diagnosed with COVID-19 and within 10 days of symptom onset. Furthermore,FDAThe infusion time for bamlanivimab monotherapy and the dual-antibody therapy of etesevimab and bamlanivimab has been approved to be shortened to 16 minutes and 21 minutes, respectively, significantly less than the previously approved 60-minute duration. This change responds to feedback from frontline nurses and physicians responsible for administering injections, aiming to alleviate the burden on the healthcare system.

etesevimab (JS016 or LY-CoV016) is a recombinant fully human monoclonal neutralizing antibody jointly developed by Junshi Biosciences and the Institute of Microbiology, Chinese Academy of Sciences (IMCAS). It specifically binds with high affinity to the receptor-binding domain of the SARS-CoV-2 surface spike protein and effectively blocks the interaction between the virus and the host cell surface receptor ACE2. Eli Lilly and Company licensed etesevimab from Junshi Biosciences, while Junshi Biosciences continues to lead development activities in the Greater China region.Eli LillyPharmaceuticals Lead Development Activities in Other Global Regions. (Bioon.com)

Original Source: Lilly, Vir Biotechnology and GSK Announce Positive Topline Data from the Phase 2 BLAZE-4 Trial Evaluating Bamlanivimab with VIR-7831 in Low-Risk Adults with COVID-19