GSK and Vir Biotechnology Announce Final Phase 3 COMET-ICE Trial Results for Sotrovimab, Showing 79% Reduction in Hospitalization or Death Risk in High-Risk COVID-19 Patients Amid Global Surge to 179 Million Cases

June 21, 2021 /BioonBIOON/ -- Currently, the COVID-19 epidemic outside China continues to spread rapidly. According to Baidu's "Real-time Novel Coronavirus Pneumonia Epidemic SituationBig DataReport》, as of 00:00 on June 22, 2021,Global cumulative confirmed cases exceeded 170 million (179.37 million), with over 3.88 million deaths.

Recently,GlaxoSmithKline(GSK) and Vir Biotechnology, Inc. announced the final confirmed results of the Phase 3 COMET-ICE study (COVID-19 Monoclonal Antibody Efficacy Trial – Intent to Care Early), which showed that:Compared with placebo,Monoclonal antibody drugsIntravenous sotrovimab (previously VIR-7831, GSK4182136) therapy significantly reduces the risk of hospitalization or death in high-risk adult outpatients with mild-to-moderate COVID-19.. In addition, the National Institutes of Health (NIH) updated its COVID-19 treatment guidelines, recommending sotrovimab for the treatment of nonhospitalized patients with mild to moderate COVID-19 at high risk of clinical progression, and noted thatSotrovimab appears to retain activity against current variants of concern and variants of interest.. GSK and Vir have initiated a Phase 3 study to evaluateIntramuscular (IM) injection of sotrovimab as a simplified dosing regimen, for the early treatment of high-risk patients with mild to moderate COVID-19.

In the COMET-ICE study,The primary efficacy analysis of all 1,057 patients demonstrated that the study met its primary endpoint: by Day 29, compared with placebo, sotrovimab significantly reduced the risk of hospitalization for more than 24 hours or all-cause mortality by 79% (adjusted relative risk reduction; p<0.001).By Day 29, among patients hospitalized for more than 24 hours for acute management of any illness or who died from any cause, there were 6 cases (1%) in the sotrovimab group and 30 cases (6%) in the placebo group. In the sotrovimab group, half of the hospitalizations were likely due to causes other than COVID-19 progression (such as small bowel obstruction, lung cancer,Diabetes mellitusfoot ulcer); whereas this was not observed in the placebo group. In the safety analysis, 1,037 patients were followed up for at least 29 days. In this study, the most common in the sotrovimab groupAdverse Reactionswere rash (1%) and diarrhea (2%), all of which were Grade 1 (mild) or Grade 2 (moderate). No other treatment-emergent adverse events (TEAEs) occurred at a higher incidence in the sotrovimab group compared with the placebo group.

GSK Senior Vice President Christopher Corsico said: "Effective treatments for individuals infected with SARS-CoV-2 remain a critical component in addressing this pandemic. We are working to increase the use of sotrovimab in the United States and globally, including evaluating the potential to simplify administration via an intramuscular formulation."

George Scangos, CEO of Vir, stated: "We are pleased that the robust interim efficacy observed in the COMET-ICE trial has now been confirmed across the full study population. These results, along with a growing number of global authorizations and the recent recommendations from the NIH COVID-19 Treatment Guidelines Panel, support our confidence in the potential role of sotrovimab in combating this pandemic."

sotrovimab (Image source: writecaliber.com)

Sotrovimab is a dual-acting monoclonal antibody with the potential to simultaneously block viral entry into healthy cells and clear infected cells.Sotrovimab binds to an epitope shared by SARS-CoV-2 and SARS-CoV-1 (the virus that causes SARS). This epitope is highly conserved, which may make the development of resistance more difficult. Incorporating Xencor’s Xtend technology, sotrovimab is also designed to achieve high concentrations in the lungs to ensure optimal penetration into SARS-CoV-2-affected airway tissues, and features an extended half-life. Sotrovimab targets a conserved epitope on the S protein that is unlikely to mutate over time. In vitro data demonstrate that sotrovimab retains activity against all known relevant variants. This indicates that sotrovimab has the potential to become an important new therapeutic option for combating the current pandemic and future coronavirus outbreaks.

In late May this year,United StatesFDAEmergency Use Authorization (EUA) granted for sotrovimab for the treatment of adult and pediatric patients (12 years of age and older, weighing at least 40 kg) with mild to moderate COVID-19, specifically: patients who test positive by direct SARS-CoV-2 viral testing and are at high risk for progression to severe COVID-19 (including hospitalization and death).

Currently, GSI and Vir are actively collaborating with government agencies worldwide to provide sotrovimab to patients in need of treatment. Both parties plan to supply the United States in the second half of 2021...FDASubmit a Biologics License Application (BLA).The European Medicines Agency (EMA) has started a rolling review of the data on sotrovimab, which will continue until there is sufficient evidence to support the submission of a formal marketing authorisation application.Their strategic manufacturing network enables them to manufacture approximately 2 million doses in the first year following U.S. EUA to support emergency supply, with approximately 450,000 doses currently available.

Image source: pharmaintelligence.informa.com

GSK and Vir also announced that the COMET clinical development program continues to advance, aiming to provide clinical evidence from multiple clinical studies within the next year: (1) COMET-PEAK is a pharmacokinetic study in patients with mild to moderate COVID-19, evaluatingIntramuscular (IM) injection of sotrovimab, this study is nearing completion, with preliminary results expected to be reported in the second half of 2021. (2) The COMET-TAIL study has been initiated. This is a Phase 3 study evaluating early treatment with intramuscular (IM) injection of sotrovimab in high-risk, non-hospitalized adult and pediatric (aged 12 years and older) patients with mild-to-moderate COVID-19; data are expected to be reported in the first half of 2022. (3) A prophylactic study is planned to be conducted in uninfected immunocompromised adults to determine whether IM injection of sotrovimab can prevent symptomatic COVID-19 infection.

GSK and Vir are committed to the ongoing evaluation of sotrovimab, as the COVID-19 landscape continues to evolve at varying rates globally and new variants continue to emerge. In vitro study data published on bioRxiv confirm that,Sotrovimab retained activity against circulating variants of concern, including Gamma (P.1), Epsilon (B.1.427/B.1.429), Delta (B.1.617.2), Iota (B.1.526), Beta (B.1.351), and Alpha (B.1.1.7) variants.GSK and Vir are continuing to evaluate through in vitro studies the ability of sotrovimab to retain activity against new and emerging variants. The clinical implications of these in vitro variant data remain unclear. (Bioon.com)

Original Source:GSK and Vir Biotechnology announce continuing progress of the COMET clinical development programme for sotrovimab