GlaxoSmithKline plc and Vir Biotechnology, Inc. announced the submission of an application to the U.S Food and Drug Administration (FDA) requesting an amendment to the Emergency Use Authorization (EUA) for sotrovimab, an investigational monoclonal antibody for the early treatment of COVID-19, to include intramuscular (IM) administration. The EUA for sotrovimab was granted by the FDA in May 2021 as an investigational single-dose intravenous (IV) (500 mg) infusion SARS-CoV-2 monoclonal antibody for the early treatment of COVID-19, and the companies are requesting an expansion to the EUA to also include IM administration (500 mg). Under the current EUA, sotrovimab can be used for the treatment of mild-to-moderate 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.

This submission is based on the Phase 3, randomized, open-label, non-inferiority COMET-TAIL [2] trial, which achieved its primary endpoint, demonstrating that 500mg IM administration of sotrovimab (n=376) was non-inferior and offered similar efficacy to 500 mg IV administration (n=378) for the early treatment of mild-to-moderate COVID-19 in high-risk, non-hospitalized adults and adolescents. Low rates of serious adverse events (=1% in both arms) were observed in the headline data. Sotrovimab is an investigational SARS-CoV-2 neutralizing 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, Inc.'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. COMET-ICE: a Phase 3, multi-center, 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 hospitalized 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); COMET-TAIL: an ongoing Phase 3, randomized, multi-center, 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-hospitalized adult and pediatric patients (12 years of age and older). The trial's primary endpoint was met, and headline data demonstrated that 500mg IM-administered sotrovimab was non-inferior and offered similar efficacy to IV administration for high-risk populations. In the IM administration (500mg) arm of the trial, there was a 2.7% rate of progression to hospitalization 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. Low rates of serious adverse events (=1% in both arms) were observed in the headline data.

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 enrollment in the 250mg arm be discontinued after a greater number of hospitalizations in that arm was noted. The 500mg dose arms were recommended to continue with enrollment as planned.

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 2, randomized, multi-center, parallel group trial evaluating IV and IM administration sotrovimab in outpatients with mild-to-moderate COVID-19. The companies plan to submit the full COMET-PEAK data set to a peer-reviewed journal for publication. Additionally, GSK and Vir are 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 occur in due course. Sotrovimab is also being studied by the University of Oxford among patients hospitalized with COVID-19 in the United Kingdom as part of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) Trial.

The following is a summary of information for sotrovimab. Healthcare providers in the U.S should review the Fact Sheets for information about the authorized use of sotrovimab and mandatory requirements of the EUA. Sotrovimab is not FDA-approved for this use.