December 02, 2021: “GlaxoSmithKline plc and Vir Biotechnology, Inc. announced an update to bioRxiv, a preprint server, with preclinical data demonstrating that sotrovimab, an investigational monoclonal antibody, retains activity against key mutations of the new Omicron SARS-CoV-2 variant (B.1.1.529), including those found in the binding site of sotrovimab.
These data were generated through pseudo-virus testing of specific individual mutations found in Omicron.
To date, sotrovimab has demonstrated ongoing activity against all tested variants of concern and interest defined by the World Health Organization (WHO).
The companies are now completing in vitro pseudo-virus testing to confirm the neutralising activity of sotrovimab against the combination of all the Omicron mutations with the intent to provide an update by the end of 2021.
George Scangos, PhD, Chief Executive Officer of Vir, said: “Sotrovimab was deliberately designed with a mutating virus in mind. By targeting a highly conserved region of the spike protein that is less likely to mutate, we hoped to address both the current SARS-CoV-2 virus and future variants that we expected would be inevitable. This hypothesis has borne out again and again – with its ongoing ability to maintain activity against all tested variants of concern and interest to date, including key mutations found in Omicron, as demonstrated by preclinical data. We have every expectation that this positive trend will continue and are working rapidly to confirm its activity against the full combination sequence of Omicron.”
Dr Hal Barron, Chief Scientific Officer and President R&D, GSK, said: “Since the beginning of the pandemic, we have been working with Vir to combine our scientific expertise and technologies to deliver an enduring treatment option for patients with COVID-19. Though early, these pre-clinical data support our long-held view on the potential for sotrovimab to maintain its activity as the virus continues to mutate. We are pleased that this treatment option is available to patients in the US and many other countries, and are working to expand access worldwide.”
About sotrovimab
Sotrovimab is an investigational SARS-CoV-2 neutralising monoclonal antibody. The antibody binds to an epitope on SARS-CoV-2 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 tested variants of concern and interest of the SARS-CoV-2 virus as defined by WHO, plus others, including but not limited to Delta (B.1.617.2), Delta Plus (AY.1 or AY.2), Mu (B.1.621) and key mutations of Omicron (B.1.1.529).
About the sotrovimab clinical development programme
- COMET-ICE: a Phase III, multi-centre, double-blind, placebo-controlled trial investigated an 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 27 October 2021 and final data were pre-published on 8 November 2021 on medRxiv.
- COMET-TAIL: a Phase III, randomised, multi-centre, open-label, non-inferiority trial of intramuscular (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 complete 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 complete COMET-PEAK data set to a peer-reviewed journal for publication in due course.
- 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 experienced investigators and networks 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 programme will take place in due course.
About global access to sotrovimab
- Sotrovimab is authorised for emergency use in the United States. Xevudy (sotrovimab) received a positive scientific opinion under Article 5(3) of Regulation 726/2004 from the Committee for Human Medicinal Products (CHMP) in the EU, has been granted a provisional marketing authorisation in Australia, and conditional marketing authorisation in Saudi Arabia. In Japan, it has been approved via the Special Approval for Emergency Pathway. Temporary authorisations for sotrovimab have been granted in a dozen countries.
- GSK and Vir also recently submitted the Marketing Authorisation Application (MAA) to the European Medicines Agency for Xevudy (sotrovimab) for the treatment of adults and adolescents (aged 12 years and over and weighing at least 40 kg) with coronavirus disease 2019 (COVID-19) who do not require oxygen supplementation and who are at risk of progressing to severe
COVID-19. - Sotrovimab is supplied in several countries worldwide, including through national agreements in the United States, United Kingdom, Japan, Australia, Canada, Singapore, Switzerland and United Arab Emirates. 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.”
https://www.gsk.com/en-gb/media/press-releases/preclinical-data-demonstrate-sotrovimab-retains-activity-against-key-omicron-mutations-new-sars-cov-2-variant/
