SYNOPSIS
- US government contracts for approximately $1 billion (USD) are now in place to purchase Sotrovimab, further expanding access nationwide
- Sotrovimab, an investigational monoclonal antibody for the early treatment of COVID-19, which the US Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) in May 2021.
- This brings the total number of doses secured through binding agreements to more than 750,000 globally
- Final data from the COMET-ICE Phase III trial showed sotrovimab reduces hospitalisation and risk of death by 79% in adults with mild-to-moderate COVID-19 who are at high risk of progression to severe disease
- In Vitro data indicate Sotrovimab maintains activity against the Delta variant of concern and other variants being monitored
GSK and Vir Biotechnology announce United States Government Agreements to Purchase Sotrovimab, a COVID-19 Treatment.
GlaxoSmithKline plc (LSE/NYSE: GSK) and Vir Biotechnology, Inc. (Nasdaq: VIR) announced US government contracts totalling approximately $1 billion[1] (USD) to purchase Sotrovimab, an investigational monoclonal antibody for the early treatment of COVID-19, which the US Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) in May 2021. GSK will supply these doses to the US government by December 17, 2021, enabling further expanded nationwide access to Sotrovimab for patients.
In addition to the doses that will be supplied this year, the US government will have the option to purchase additional doses through March 2022.
Including the contracts announced today, GSK and Vir have received binding agreements for the sale of more than 750,000 doses of Sotrovimab worldwide, with additional doses reserved through other agreements including the previously announced Joint Procurement Agreement with the European Commission.
Sotrovimab is an FDA EUA authorised investigational single-dose intravenous (IV) infusion SARS-CoV-2 monoclonal antibody. Under the EUA, Sotrovimab can be used for the treatment of mild-to-moderate COVID-19 in adults and paediatric patients (12 years of age and older weighing at least 40 kg) with positive test results for COVID-19, and who are at high risk for progression to severe COVID-19, including hospitalisation or death.
Dr Hal Barron, Chief Scientific Officer and President R&D, GSK, said: “Given the large number of patients who continue to become ill with COVID-19 across many regions in the US, there is an ongoing need for access to effective treatments. We are proud to work with the US government to help make Sotrovimab available for these patients.”
George Scangos, Ph.D., Chief Executive Officer of Vir, said: “Monoclonal antibodies play an essential role in the treatment of certain patients with COVID-19, and we’re grateful that this agreement will allow more healthcare providers and patients who are at high risk for progression to severe COVID-19 to access Sotrovimab. Given ongoing evidence, which demonstrates its ability to maintain activity against the tested circulating variants of concern, including Delta, we are confident Sotrovimab will continue to be important in the fight against COVID-19.”
The US government purchase was funded by the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response through Department of Defense – contract numbers W58P0521C0008 and W58P0522C0002.
In June 2021, GSK and Vir announced confirmatory full results for the COMET-ICE Phase III trial, which resulted in a 79% reduction (adjusted relative risk reduction) (p<0.001) in hospitalisations 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 companies also recently announced headline data from the randomised, multi-centre, open-label COMET-TAIL Phase III trial, which achieved its primary endpoint, demonstrating intramuscular (IM) administration of sotrovimab was non-inferior to IV administration for the early treatment of mild-to-moderate COVID-19 in high-risk, non-hospitalised adults and adolescents (12 years of age and older). The companies plan to progress regulatory submissions globally.
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. Updated in vitro data, published in bioRxiv, demonstrate that sotrovimab retains activity against all current variants of concern and interest of the SARS-CoV-2 virus as defined by the World Health Organization, plus others, including, but not limited to, Delta (B.1.617.2), Delta Plus (AY.1 or AY.2) and Mu (B.1.621).
About Sotrovimab:
Sotrovimab is an investigational SARS-CoV-2 neutralising monoclonal antibody. 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, has also 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.
It is under development by GlaxoSmithKline and Vir Biotechnology, Inc.
Sotrovimab is designed to attach to the spike protein of SARS-CoV-2.
Pharmacology
Mechanism of Action (MOA):
Recombinant human IgG1-kappa monoclonal antibody
Binds to a conserved epitope on the spike protein receptor binding domain of SARS-CoV-2 with a dissociation constant KD = 0.21 nM) but does not compete with human ACE2 receptor binding (IC50 value >33.6 nM [5 mcg/mL])
Inhibits an undefined step that occurs after virus attachment and before fusion of the viral and cell membranes
Absorption
Peak plasma concentration
- Following 1-hr infusion: 137 mcg/mL
- Day 29: 34 mcg/mL
Dosing Considerations
Circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies
Benefit of treatment with sotrovimab has not been observed in patients hospitalized for 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
Limitations of use
- Benefit of treatment not observed in patients hospitalized due to COVID-19
- Monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation
· Not authorized for use in patients
- Who are hospitalized with COVID-19, OR
- Who require oxygen therapy for COVID-19, OR
- Who require an increase in baseline oxygen flow rate because of COVID-19 (in those on long-term oxygen therapy for underlying non-COVID-19–related comorbidity)
Patient selection
- Obesity/overweight (body mass index [BMI] ≥25 kg/m2 [adults]; BMI ≥85th percentile for age/sex based on CDC growth charts [if aged 12-17 years])
- Pregnancy
- Chronic kidney disease
- Diabetes
- Immunosuppressive disease or immunosuppressive treatment
- Cardiovascular disease (including congenital heart disease) or hypertension
- Chronic lung diseases (eg, chronic obstructive pulmonary disease [COPD], moderate-to-severe asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension)
- Sickle cell disease
- Neurodevelopmental disorders (eg, cerebral palsy) or other conditions that confer medical complexity (eg, genetic or metabolic syndromes, severe congenital anomalies)
- Having a medical-related technological dependence (eg, tracheostomy, gastrostomy, positive-pressure ventilation [not related to COVID 19])
- EUA is not limited to the medical conditions or factors listed above; for additional information on medical conditions and factors associated with increased risk for progression to severe COVID,
Warnings
Contraindications
None
Cautions
Hypersensitivity
- Serious hypersensitivity reaction, including anaphylaxis, may occur
- Hypersensitivity reactions occurring more >24 hr after the infusion have also been reported with SARS-CoV-2 monoclonal antibodies under EUA
- If signs and symptoms occur, immediately discontinue IV infusion, and initiate appropriate medications and/or supportive care
- Infusion-related reactions reported, including 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, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, dizziness, and diaphoresis
Clinical worsening after administration
- Clinical worsening of COVID-19 after administration reported; signs or symptoms may include fever, hypoxia or increased respiratory difficulty, arrhythmia (eg, atrial fibrillation, sinus tachycardia, bradycardia), fatigue, and altered mental status
- Some of these events required hospitalization
- Unknown if these events were related to the monoclonal antibodies or were due to progression of COVID-19
Severe COVID-19
- Treatment benefit not observed in patients hospitalized with COVID-19
- 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, use is not authorized for use in patients
- Who are hospitalized with COVID-19, OR
- Who require oxygen therapy for COVID-19, OR
- Who require an increase in baseline oxygen flow rate because of COVID-19 (in those on long-term oxygen therapy for underlying non-COVID-19–related comorbidity)
Viral variants
- Circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies
- Prescribing clinicians should consider prevalence of etesevimab resistant variants in their area
- Healthcare providers should review antiviral resistance information provided by state and local health departments
- Variant proportions circulating in the United States can be monitored at the CDC website
· Pseudotyped viruslike particle neutralization data of sotrovimab (May, 2021)
- 1.1.7 (UK origin): No change: <5-fold reduction in susceptibility
- 1.351 (South Africa origin): No change: <5-fold reduction in susceptibility
- 1 (Brazil origin): No change: <5-fold reduction in susceptibility
- 1.427/B.1.429 (California origin): No change: <5-fold reduction in susceptibility
- 1.526 (New York origin): No change: <5-fold reduction in susceptibility
· Authentic SARS-CoV-2 neutralization data of sotrovimab (May, 2021)
- 1.1.7 (UK origin): No change: <5-fold reduction in susceptibility
- 1.351 (South Africa origin): No change: <5-fold reduction in susceptibility
- 1 (Brazil origin): No change: <5-fold reduction in susceptibility
Drug interaction overview
- Not renally excreted or metabolized by CYP450 enzymes
- Interactions with concomitant renally excreted drugs or drugs that are CYP450 substrates, inducers, or inhibitors are unlikely
Pregnancy & Lactation
Pregnancy
Insufficient data to evaluate drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
Use during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus
No dosage adjustment recommended by the manufacturer
Nonclinical reproductive toxicity studies have not been conducted
Sotrovimab is an Fc-enhanced human IgG and may have the potential for placental transfer from mother to developing fetus
Lactation
Data are unknown regarding presence in human or animal milk, effects on breastfed infants, or effects on milk production
Maternal IgG is known to be present in human milk
No dosage adjustment recommended by the manufacturer
About global access to Sotrovimab:
Sotrovimab is authorised for emergency use in the United States and received a positive scientific opinion under Article 5(3) of Regulation 726/2004 from the Committee for Human Medicinal Products (CHMP) in the European Union (EU). Sotrovimab has been granted a provisional marketing authorisation in Australia and a conditional marketing authorisation in Saudi Arabia. In Japan, it has been approved via the Special Approval for Emergency Pathway. Temporary authorisations have been granted in Bahrain, Brazil, Canada, Egypt, Italy, Kuwait, Oman, Qatar, Singapore, Switzerland, Thailand and the United Arab Emirates (UAE).
Sotrovimab is supplied in several countries around the world, including through national agreements in the United States, Japan, Australia, Canada, Singapore and the UAE. We have also signed a Joint Procurement Agreement with the European Commission to supply doses of sotrovimab. Additional agreements are yet to be announced due to confidentiality or regulatory requirements.
About the sotrovimab clinical development programme:
COMET-ICE: a Phase III, multi-centre, double-blind, placebo-controlled trial investigated IV infusion of sotrovimab in adults with mild-to-moderate COVID-19 at high-risk of progression to severe disease, who are not hospitalised and not requiring oxygen. The final COMET-ICE trial results in the full trial population of 1,057 participants demonstrated a 79% reduction (adjusted relative risk reduction) (p<0.001) in hospitalisation for more than 24 hours or death due to any cause by Day 29 compared to placebo, meeting the primary endpoint of the trial. Interim data were published in The New England Journal of Medicine on October 27, 2021 and final data were pre-published on November 8, 2021 on medRxiv.
COMET-TAIL: a Phase III, randomised, multi-centre, open label, non-inferiority trial of IM versus IV administration of sotrovimab for the early treatment of mild-to-moderate COVID-19 in high-risk non-hospitalised adult and paediatric patients (12 years of age and older). The trial’s primary endpoint was met, and headline data demonstrated that intramuscularly administered sotrovimab was non-inferior and offered similar efficacy to intravenous administration for high-risk populations. The companies plan to submit the full COMET-TAIL data set to a peer-reviewed journal for publication in the first quarter of 2022.
COMET-PEAK: a Phase II, randomised, multi-centre, parallel group trial evaluating IV and IM administration of sotrovimab in outpatients with mild-to-moderate COVID-19. Data available to date from open label Part B of the trial (500mg IV vs. 500mg IM) demonstrated equivalence on the virological response between the IM and IV arms. The companies plan to submit the full COMET-PEAK data set to a peer-reviewed journal for publication.
GSK and Vir are also partnering to investigate the use of sotrovimab in uninfected immunocompromised adults to determine whether sotrovimab can prevent symptomatic COVID-19 infection. GSK and Vir are supporting investigator sponsored studies and fostering scientific collaborations with both experienced investigators and networks, who are involved in the continuum of care of immunocompromised patients, to understand the role sotrovimab for prophylaxis could play in this population. Discussions with regulatory authorities regarding the prophylaxis program will take place in due course.
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 potential treatments in addition to our vaccine candidates in development with partner organisations.
GSK is collaborating with several organisations on COVID-19 vaccines by providing access to our adjuvant technology. We are working with Sanofi, Medicago and SK bioscience to develop adjuvanted, protein-based vaccine candidates, and all are now in Phase III clinical trials. 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 protect more people in need.
GSK is also working with mRNA specialist, CureVac, to jointly develop next generation, optimised mRNA vaccines for COVID-19 with the potential to address multiple emerging variants in one vaccine.
GSK is also exploring treatments for COVID-19 patients, collaborating with Vir Biotechnology to investigate monoclonal antibodies that could be used as therapeutic or preventive options for COVID-19.
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. GlaxoSmithKline plc (GSK) is a British multinational pharmaceutical company headquartered in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham, GSK was the world’s sixth largest pharmaceutical company according to Forbes as of 2019, after Pfizer, Novartis, Roche, Sanofi, and Merck & Co. GSK is the tenth largest pharmaceutical company and #296 on the 2019 Fortune 500, ranked behind other pharmaceutical companies including China Resources, Johnson & Johnson, Roche, Sinopharm, Pfizer, Novartis, Bayer, Merck, and Sanofi.
The company has a primary listing on the London Stock Exchange and is a constituent of the FTSE 100 Index. As of August 2016, it had a market capitalisation of £81 billion (about US$107 billion), the fourth largest on the London Stock Exchange. It has a secondary listing on the New York Stock Exchange.
The company developed the first malaria vaccine, RTS,S, which it said in 2014 it would make available for five percent above cost. Legacy products developed at GSK include several listed in the World Health Organization’s List of Essential Medicines, such as amoxicillin, mercaptopurine, pyrimethamine, and zidovudine.
About Vir Biotechnology:
Vir Biotechnology is a commercial-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.