GSK and Vir Biotechnology announce sotrovimab (VIR-7831) receives Emergency Use Authorization from the US FDA for treatment of mild-to-moderate COVID-19 in high-risk adults and paediatric pat
GlaxoSmithKline plc (LSE/NYSE: GSK) and Vir Biotechnology, Inc. (Nasdaq: VIR) today announced the U.S. Food and Drug Administration (FDA) granted an Emergency Use Authorization (EUA) for sotrovimab (previously VIR-7831), an investigational single-dose monoclonal antibody, 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 results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalisation or death.
Adrienne E. Shapiro, M.D., Ph.D.,?an infectious disease specialist at?Fred Hutchinson Cancer Research Center and investigator in the COMET-ICE trial, said:??Monoclonal antibodies like sotrovimab are potentially one of our most effective tools for fighting COVID-19. While preventive measures, including vaccines, can reduce the total number of cases, sotrovimab is an important treatment option for those who become ill with COVID-19 and are at high risk ? allowing them to avoid hospitalisation or worse.?
George Scangos, Ph.D., Chief Executive Officer of Vir, said:??Our distinctive scientific approach has led to a single monoclonal antibody that, based on an interim analysis, resulted in an 85% reduction in all-cause hospitalisations or death, and has demonstrated, in vitro, that it retains activity against all known variants of concern, including the emerging variant from India. I believe that sotrovimab is a critical new treatment option in the fight against the current pandemic and potentially for future coronavirus outbreaks, as well. At Vir, our aim is not only to deliver a clinically effective therapy for COVID-19, but also to provide effective therapy against SARS-CoV-2 variants and potential pandemics of tomorrow.?
Dr Hal Barron, Chief Scientific Officer and President R&D, GSK, said:??The fast pace of COVID-19 vaccinations in the U.S. is encouraging, yet, despite these aggressive efforts, there is still a need to help prevent infected patients from developing complications. In just over a year since starting our collaboration and in less than 10 months since beginning clinical trials, we are delighted that, as of today, the benefits of this unique monoclonal antibody will now be available to patients in need.?
Sotrovimab has been granted an EUA by the FDA to facilitate the availability and use of this investigational monoclonal antibody for the treatment of COVID-19 in the U.S. while the pandemic remains a public health emergency. The?FDA Fact Sheet for Healthcare Providers?regarding the emergency use of sotrovimab reflects the recently updated definition of high risk for COVID-19 to include additional medical conditions and factors associated with increased risk for progression to severe disease. The EUA for sotrovimab also includes post-authorisation commitments as specified in the?Letter of Authorization.
Sotrovimab is continuing to be studied in ongoing clinical trials. An analysis of safety and efficacy data at day 29 for the full population from the COMET-ICE trial is expected as early as the first half of 2021. GSK and Vir plan to submit a Biologics License Application (BLA) to the FDA in the second half of 2021.
Evidence of Sotrovimab?s Profound Clinical Efficacy
The EUA was granted to sotrovimab based on an interim analysis of efficacy and safety data from the Phase 3 COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial ? Intent to Care Early) trial in high-risk adult outpatients, which was stopped early by an independent data monitoring committee in March 2021 due to evidence of profound clinical efficacy. As previously announced, interim study results demonstrated an 85% (p=0.002) reduction in hospitalisation for more than 24 hours or death in those receiving sotrovimab compared to placebo, the primary endpoint of the trial. The most common adverse events observed in the sotrovimab treatment group in COMET-ICE were rash (2%) and diarrhoea (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. The EUA includes a warning for hypersensitivity including anaphylaxis and infusion-related reactions.In Vitro Data Indicate Sotrovimab Maintains Activity Against All Known Variants of Concern
Sotrovimab targets a conserved epitope of the spike protein that is less likely to mutate over time. The EUA submission also included data from published in vitro studies, which demonstrated that sotrovimab maintains activity against all known circulating variants of concern, including the variants from Brazil (P.1), California (B.1.427/B.1.429), India (B.1.617), New York (B.1.526), South Africa (B.1.351) and the UK (B.1.1.7). GSK and Vir will continue to evaluate the ability of sotrovimab to maintain activity against new and emerging variants. The clinical impact of these in vitro variant data is not yet known. Data collection and analysis is still ongoing.GSK and Vir?s Commitment to Patient Access to Sotrovimab
GSK and Vir are actively working with government agencies around the world to make sotrovimab available to patients in need of treatment.- On 21 May 2021, the European Medicines Agency?s (EMA) Committee for Human Medicinal Products (CHMP) issued a positive scientific opinion following the referral of sotrovimab to the CHMP under Article 5(3) of Regulation 726/2004. The opinion relates to the use of sotrovimab for the treatment of adults and adolescents (aged 12 years and over and weighing at least 40 kg) with COVID-19 who do not require oxygen supplementation and who are at risk of progressing to severe COVID-19.
- The EMA has also started a rolling review of data on sotrovimab that will continue until enough evidence is available to support the filing of a formal marketing authorisation application.
- In April, Health Canada initiated a review of sotrovimab under the expedited Interim Order application pathway for COVID-19 drugs.
- GSK and Vir?are continuing discussions with other global regulators?on the regulatory pathways available so that?sotrovimab?can be made available to patients with COVID-19 as soon as possible.
About the COMET-ICE Study Design
The multi-center, double-blind, placebo-controlled, Phase 3 COMET-ICE trial investigated intravenous (IV) infusion of sotrovimab in adults with mild or moderate COVID-19 at high risk of progression to severe disease. This ongoing trial evaluated the safety and efficacy of a single IV infusion of sotrovimab (500 mg) or placebo in non-hospitalised participants globally. The safety of sotrovimab is primarily based on an interim analysis from 868 patients (430 patients in the treatment arm and 438 in the placebo arm) through day 15. Among those studied, 63% were Hispanic or Latino and 7% were Black or African American. According to the Centers for Disease Control and Prevention, these populations are approximately three times more likely to be hospitalised and approximately two times more likely to die of COVID-19[1]. The primary efficacy endpoint was the proportion of patients who have progression of COVID-19 as defined by the need for hospitalisation for greater than 24 hours for acute management of illness or death. In March 2021, an Independent Data Monitoring Committee recommended that the COMET-ICE trial be stopped for enrolment due to evidence of profound efficacy.About the Sotrovimab Clinical Development Program
In addition to the COMET-ICE trial, the full COMET clinical development program for sotrovimab includes:- COMET-PEAK: An ongoing Phase 2 trial with two parts: to compare the safety and viral kinetics of 500 mg intramuscularly (IM) administered sotrovimab to 500 mg intravenously administered sotrovimab among low-risk adults with mild to moderate COVID-19 and to evaluate the similarity in pharmacokinetics between sotrovimab manufactured by different processes
- COMET-TAIL: A Phase 3 trial expected to begin in the second quarter of 2021 as an early treatment for COVID-19 in high-risk adults, to assess whether IM-administered sotrovimab can reduce hospitalisation or death due to COVID-19
- COMET-STAR: A Phase 3 trial expected to begin in the second half of 2021 in uninfected adults at high risk to determine whether IM-administered sotrovimab can prevent symptomatic infection.
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.About VIR-7832 / GSK4182137
VIR-7832 is an investigational dual-action SARS-CoV-2 monoclonal antibody. Preclinical data suggest it has the potential to both block viral entry into healthy cells and an enhanced ability to 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. VIR-7832, which incorporates Xencor?s Xtend and other Fc technologies, 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. Importantly, VIR-7832 also has been engineered to potentially enhance virus-specific T cell function, which could help treat and/or prevent COVID-19 infection. The following is a summary of information for sotrovimab. Healthcare providers 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.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).