Primary endpoint met in COMET-TAIL Phase III trial evaluating intramuscular administration of sotrovimab for early treatment of COVID-19

GlaxoSmithKline plc (LSE/NYSE: GSK) and Vir Biotechnology, Inc. (Vir) (Nasdaq: VIR) 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 intravenous (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 COMET-TAIL Phase III trial was designed to evaluate the efficacy, safety, and tolerability of sotrovimab delivered via IM administration compared to IV administration in high-risk patients up to seven days after symptom onset. In the IM administration (500mg) arm of the trial, there was a 2.7% rate of progression to hospitalisation for more than 24 hours or death through Day 29 of the trial, compared to 1.3% in the IV administration arm (also 500mg). The adjusted difference between the IM and IV arms of the trial was 1.07% with a 95% confidence interval (CI) of -1.25% to 3.39%. The upper bound of the 95% CI is within the predetermined 3.5% non-inferiority margin set for the trial’s primary endpoint in consultation with the US Food and Drug Administration (FDA).

In addition, there were low rates of serious adverse events and Grade 3-4 adverse events (≤1% in both arms, for both measures) observed in the headline data.

The companies plan to progress regulatory submissions globally, including ongoing discussions with the FDA regarding the existing Emergency Use Authorization for sotrovimab.

Dr Hal Barron, Chief Scientific Officer and President, said: "I am pleased that today's results demonstrated similar efficacy for sotrovimab when injected directly into the muscle compared to administered intravenously, potentially offering a more convenient option for patients. We look forward to working with regulatory authorities to help make this new option available to appropriate patients with COVID-19."

George Scangos, Ph.D., chief executive officer of Vir, said: "This trial was conducted during the height of circulation of the Delta variant, with significant enrollment in Florida - a hot spot for this particular variant and where hospitalisation rates averaged more than 10 percent of confirmed cases. We designed sotrovimab to stand up to the variants that we anticipated would occur, and these data demonstrate that sotrovimab administered via IV or IM could prove important in the fight against COVID-19 following authorisation. As we approach the third year of the pandemic, we can expect that multiple treatment options will continue to be needed, particularly for high-risk patients with complex health needs."

Today's update follows announcements in the first half of 2021 regarding the COMET-ICE Phase III trial, which investigated IV infusion of sotrovimab in adults with mild or moderate COVID-19 at high-risk of progression to severe disease. The final COMET-ICE trial results in the full study population of 1057 participants, demonstrated a 79% reduction in hospitalisation and death at Day 29 vs placebo.

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.

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 Organisation, 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 the sotrovimab clinical development programme

COMET-ICE: a Phase III, multi-centre, double-blind, placebo-controlled trial investigated intravenous (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 intramuscular (IM) versus intravenous (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 COMET-TAIL trial enrolled a total of 983 patients up to seven days after onset of symptoms. The trial originally included three arms: 500mg of sotrovimab given intravenously, and two intramuscular arms, consisting of 500mg and a low dose of 250mg. An independent safety monitoring committee recommended enrolment in the 250mg arm be discontinued after a greater number of hospitalisations in that arm was noted. The 500mg dose arms were recommended to continue with enrolment as planned. 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, while also showing an acceptable tolerability profile for IM with only 10/82 participants (12%) reporting any injection site reaction, all of which were low grade (Grade 1). 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 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 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.

• Sotrovimab is supplied in several countries around the world, including through national agreements in the United States, Japan, Australia, Canada, Singapore and 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 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 SARSCoV-2 and future coronavirus pandemics, both independently and in collaboration with its partners.

About GSK

GSK is a science-led global healthcare company.

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.