GSK and Vir Biotechnology Announce Continuing Progress of the COMET Clinical Development Program for Sotrovimab

– Analysis of final Day 29 data from COMET-ICE confirms sotrovimab significantly reduces 
hospitalization and risk of death in adults with mild-to-moderate COVID-19 who are at high risk 
of progression to severe disease –

– U.S. National Institutes of Health (NIH) COVID-19 Treatment Guidelines
updated to recommend use of sotrovimab –

– Further research initiated to evaluate intramuscular administration of sotrovimab for the
early treatment of mild-to-moderate COVID-19 in high-risk patients in a Phase 3 study –

LONDON and SAN FRANCISCO, June 21, 2021 (GLOBE NEWSWIRE) -- GlaxoSmithKline plc (LSE/NYSE: GSK) and Vir Biotechnology, Inc. (Nasdaq: VIR) today announced final, confirmatory results from the Phase 3 COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial – Intent to Care Early) trial demonstrating that sotrovimab, an investigational SARS-CoV-2 monoclonal antibody, significantly reduced the risk of hospitalization or death among high-risk adult outpatients with mild-to-moderate COVID-19. Additionally, the U.S. National Institutes of Health (NIH) updated its COVID-19 treatment guidelines to recommend sotrovimab for non-hospitalized patients with mild-to-moderate COVID-19 who are at high risk of clinical progression and noted that sotrovimab appears to retain activity against current variants of concern and interest.

The primary efficacy analysis of all 1,057 patients in the COMET-ICE trial demonstrated a 79% reduction (adjusted relative risk reduction) (p<0.001) in hospitalization for more than 24 hours or death due to any cause, by Day 29 compared to placebo, meeting the primary endpoint of the trial.

The number of patients in the trial who were hospitalized for >24 hours for acute management of any illness or death from any cause at Day 29 was six patients in the sotrovimab arm (1%), versus 30 patients in the placebo arm (6%). In the sotrovimab arm, it is possible that half of those patients who were hospitalized were for reasons other than progression of COVID-19 (e.g., small bowel obstruction, lung cancer and diabetic foot ulcer); this was not the case for patients in the placebo arm. In the safety analysis, 1,037 participants were followed through at least 29 days. The most common adverse events observed in the sotrovimab treatment group in COMET-ICE were rash (1%) and diarrhea (2%), all of which were Grade 1 (mild) or Grade 2 (moderate). No other treatment-emergent adverse events were reported at a higher rate with sotrovimab compared to placebo. The companies plan to submit the full COMET-ICE data set to a peer-reviewed journal for publication.

Christopher Corsico, senior vice president of development, GSK, said: “Effective medicines to treat those who become infected with SARS-CoV-2 remain a critical part of the solution to this pandemic. We are working diligently to increase access to sotrovimab in the U.S. and across the globe, including evaluating the potential to simplify administration with an intramuscular formulation.”

George Scangos, Ph.D., chief executive officer of Vir, said: “We are pleased that the profound interim efficacy from the COMET-ICE trial has now been validated by the full study population. These results, combined with the growing number of pending global authorizations, as well as the recent recommendation by the NIH COVID-19 Treatment Guidelines Panel, support our confidence in the potential role of sotrovimab in the fight against this pandemic.”

Updated NIH Guidelines Recommend Sotrovimab
The NIH recently updated its guidelines regarding the emergency use authorizations of anti-SARS-CoV-2 monoclonal antibodies for the treatment of COVID-19 in the U.S. to recommend the use of sotrovimab for non-hospitalized patients with mild-to-moderate COVID-19 who are at high risk of clinical progression. The guidelines note that the target binding site of sotrovimab is in a region of the virus that does not overlap with the binding site location of key mutations in current variants of concern and interest. These guidelines were based upon an interim analysis of 583 patients in the COMET-ICE trial, which was stopped early in March 2020 by an independent data monitoring committee because interim results demonstrated evidence of sotrovimab’s clinical efficacy. The interim study results demonstrated an 85% (p=0.002) reduction in hospitalization for more than 24 hours or death in those receiving sotrovimab compared to placebo, the primary endpoint of the trial.

These data have informed global regulatory reviews to date, including the positive scientific opinion issued by the European Medicines Agency’s (EMA) Committee for Human Medicinal Products (CHMP) under Article 5(3) of Regulation 726/2004, as well as the Emergency Use Authorization (EUA) granted by the U.S. Food and Drug Administration (FDA).

The companies are actively working with government agencies around the world to make sotrovimab available to patients in need of treatment.

• GSK and Vir plan to submit a Biologics License Application (BLA) to the U.S. FDA in the second half of 2021.
• The EMA has started a rolling review of data on sotrovimab that will continue until enough evidence is available to support the filing of a formal marketing authorization application.
• The companies’ strategic manufacturing network is enabling the manufacture of approximately two million doses to support emergency supply in the first year following U.S. Emergency Use Authorization, with approximately 450,000 doses on hand.
  

Continued Progress with the COMET Clinical Development Program
The companies are also pleased to announce continued progress with the robust COMET clinical development program, which aims to provide clinical evidence from several studies over the course of the next year.

• COMET-PEAK, a pharmacokinetic study in outpatients with mild-to-moderate COVID-19 investigating intramuscular (IM) administration of sotrovimab, is near completion and initial data is expected in second half of 2021.
• COMET-TAIL has been initiated. This is a Phase 3 study evaluating the role of IM-administered sotrovimab for the early treatment of mild-to-moderate COVID-19 in high-risk non-hospitalized adult and pediatric patients (12 years of age and older). Data are anticipated in the first half of 2022.
• A prophylaxis study is planned in uninfected immunocompromised adults to determine whether IM-administered sotrovimab can prevent symptomatic COVID-19 infection.
  

GSK and Vir are committed to ongoing evaluation of sotrovimab as the COVID-19 landscape continues to evolve at different rates across the globe and new variants of concern and interest emerge. Data from in vitro studies, published in bioRxiv, have demonstrated that sotrovimab maintains activity against circulating variants of concern and interest, including the Gamma (P.1), Epsilon (B.1.427/B.1.429), Delta (B.1.617.1), Iota (B.1.526), Beta (B.1.351) and Alpha (B.1.1.7) variants. GSK and Vir are continuing to evaluate the ability of sotrovimab to maintain activity against new and emerging variants through in vitro studies. The clinical impact of this in vitro variants data is not yet known.

About Sotrovimab (previously VIR-7831)
Sotrovimab is an investigational 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. Sotrovimab, 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.

The following is a summary of information for sotrovimab. Healthcare providers in the U.S. should review the Fact Sheets for information on the authorized use of sotrovimab and mandatory requirements of the EUA. Please see the FDA Letter of Authorization, Fact Sheet for Healthcare Providers, and Fact Sheet for Patients, Parents, and Caregivers. For more information on the EMA positive scientific opinion, please review the EU Conditions of Use.

Important Information about Sotrovimab
Sotrovimab has been authorized by the FDA for the emergency use described below. Sotrovimab is not FDA-approved for this use. 

Sotrovimab is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of sotrovimab under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner. 

Authorized Use 
The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) to permit the emergency use of the unapproved product sotrovimab for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.

Limitations of Authorized Use 
Sotrovimab is not authorized for use in patients: 

• who are hospitalized due to COVID-19, OR 
• who require oxygen therapy due to COVID-19, OR 
• who require an increase in baseline oxygen flow rate due to COVID-19 (in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity). 
  

Benefit of treatment with sotrovimab has not been observed in patients hospitalized due to COVID-19. SARS-CoV-2 monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation.

Important Safety Information for Sotrovimab

Warnings

There are limited clinical data available for sotrovimab. Serious and unexpected adverse events may occur that have not been previously reported with sotrovimab use.

Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions

Serious hypersensitivity reactions, including anaphylaxis have been observed with administration of sotrovimab. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care.

Infusion-related reactions, occurring during the infusion and up to 24 hours after the infusion, have been observed with administration of sotrovimab. These reactions may be severe or life threatening.

Signs and symptoms of infusion-related reactions may include: fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia (eg, atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, nausea, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, vaso-vagal reactions (eg, pre-syncope, syncope), dizziness and diaphoresis.

Consider slowing or stopping the infusion and administer appropriate medications and/or supportive care if an infusion-related reaction occurs.

Hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of SARS-CoV-2 monoclonal antibodies under Emergency Use Authorization.

Clinical Worsening After SARS-CoV-2 Monoclonal Antibody Administration

Clinical worsening of COVID-19 after administration of SARS-CoV-2 monoclonal antibody treatment has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmia (eg, atrial fibrillation, tachycardia, bradycardia), fatigue, and altered mental status. Some of these events required hospitalization. It is not known if these events were related to SARS-CoV-2 monoclonal antibody use or were due to progression of COVID-19.

Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19

Benefit of treatment with sotrovimab has not been observed in patients hospitalized due to COVID-19. SARS-CoV-2 monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation. Therefore, sotrovimab is not authorized for use in patients: who are hospitalized due to COVID-19, OR who require oxygen therapy due to COVID-19, OR who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity.

ADVERSE EVENTS

The most common treatment-emergent adverse events observed in the sotrovimab treatment group in COMET-ICE were rash (2%) and diarrhea (1%), all of which were Grade 1 (mild) or Grade 2 (moderate). No other treatment-emergent adverse events were reported at a higher rate with sotrovimab compared to placebo.

USE IN SPECIFIC POPULATIONS

Pregnancy

There are insufficient data to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcome. Sotrovimab should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.

Lactation

There are no available data on the presence of sotrovimab in human milk, the effects on the breastfed infant, or the effects on milk production. Individuals with COVID-19 who are breastfeeding should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.

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 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.

GSK Commitment to Tackling COVID-19
GSK’s response to COVID-19 has been one of the broadest in the industry, with three potential treatments in addition to our vaccine candidates in development with partner organizations.

GSK is collaborating with several organizations on COVID-19 vaccines by providing access to our adjuvant technology. In addition to our work with Medicago, we recently announced positive Phase 2 data from our collaboration with Sanofi to develop an adjuvanted, protein-based vaccine candidate and expect to begin a Phase 3 trial in Q2. An earlier stage collaboration with SK Bioscience is also ongoing. SK Bioscience receives funding from CEPI and the Bill and Melinda Gates Foundation to develop differentiated, affordable COVID-19 vaccines for supply globally through the COVAX facility. The use of an adjuvant can be of particular importance in a pandemic since it may reduce the amount of vaccine protein required per dose, allowing more vaccine doses to be produced and contributing to protecting more people.

GSK is also working with mRNA specialist, CureVac, to jointly develop next generation, multi-valent mRNA vaccines for COVID-19 with the potential to address multiple emerging variants in one vaccine. GSK will also support manufacturing of up to 100m doses of CureVac’s first generation COVID-19 vaccine. GSK is also providing manufacturing support for up to 60m doses of Novavax’ COVID-19 vaccine in the UK.

GSK is also exploring potential therapeutic or treatment options for COVID-19 patients. We are collaborating with Vir Biotechnology to develop existing and identify new anti-viral antibodies that could be used as therapeutic or preventive options for COVID-19. We reported that an Independent Data Monitoring Committee recommended that the Phase 3 COMET-ICE trial evaluating sotrovimab as monotherapy for the early treatment of COVID-19 in adults at high risk of hospitalization be stopped for enrollment due to evidence of profound efficacy, based on an interim analysis of data from the trial. An analysis of data through Day 29 of the COMET-ICE trial was consistent with interim results. We have received Emergency Use Authorization in the U.S. and are seeking authorizations in other countries. We are also assessing whether an investigational monoclonal antibody, otilimab, can help severely ill COVID-19 patients aged over 70 who experience an overreaction of their immune system.

Vir’s Commitment to COVID-19
Vir was founded with the mission of addressing the world’s most serious infectious diseases. In 2020, Vir responded rapidly to the COVID-19 pandemic by leveraging our unique scientific insights and industry-leading antibody platform to explore multiple monoclonal antibodies as potential therapeutic or preventive options for COVID-19. Sotrovimab is the first SARS-CoV-2-targeting antibody Vir advanced into the clinic. It was carefully selected for its demonstrated promise in preclinical research, including an anticipated high barrier to resistance and potential ability to both block the virus from entering healthy cells and clear infected cells. Vir is continuing to pursue novel therapeutic and prophylactic solutions to combat SARS-CoV-2 and future coronavirus pandemics, both independently and in collaboration with its partners.

About GSK
GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.gsk.com/about-us.

About Vir Biotechnology

Vir Biotechnology is a clinical-stage immunology company focused on combining immunologic insights with cutting-edge technologies to treat and prevent serious infectious diseases. Vir has assembled four technology platforms that are designed to stimulate and enhance the immune system by exploiting critical observations of natural immune processes. Its current development pipeline consists of product candidates targeting COVID-19, hepatitis B virus, influenza A and human immunodeficiency virus. For more information, please visit www.vir.bio.

GSK Cautionary Statement Regarding Forward-Looking Statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described in the Company's Annual Report on Form 20-F for 2020 and any impacts of the COVID-19 pandemic.

Vir Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “plan,” “potential,” “aim,” “promising” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Vir’s expectations and assumptions as of the date of this press release. Forward-looking statements contained in this press release include, but are not limited to, statements regarding the final data from the COMET-ICE trial, NIH guidelines recommending the use of sotrovimab in the treatment of COVID-19, the initiation of Vir’s COMET-TAIL clinical trial, the clinical development program for sotrovimab, Vir’s capacity to manufacture and supply sotrovimab, the ability of sotrovimab to treat and/or prevent COVID-19, the ability of sotrovimab to maintain activity against circulating variants of concern, and statements related to regulatory authorizations and approvals, including plans and discussions with the FDA, EMA and other global regulators. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during preclinical or clinical studies, challenges in the treatment of hospitalized patients, difficulties in collaborating with other companies or government agencies, challenges in accessing manufacturing capacity, successful development and/or commercialization of alternative product candidates by Vir’s competitors, changes in expected or existing competition, delays in or disruptions to Vir’s business or clinical trials due to the COVID-19 pandemic, geopolitical changes or other external factors, and unexpected litigation or other disputes. Other factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Vir’s filings with the U.S. Securities and Exchange Commission, including the section titled “Risk Factors” contained therein. Except as required by law, Vir assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

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