GSK and VIR Biotechnology EMA Rolling Review of VIR-7831 (Sotrovimab)

GlaxoSmithKline plc and Vir Biotechnology, Inc. today announced that the European Medicines Agency (EMA) has started a rolling review of data on sotrovimab (previously VIR-7831), an investigational dual-action SARS-CoV-2 monoclonal antibody, 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.

The EMA will evaluate all data on sotrovimab, including evidence from clinical trials, as they become available. The rolling review will continue until enough evidence is available to support a formal marketing authorisation application. The EMA will assess the medicine’s compliance with the usual standards for efficacy, safety and quality. While the overall review timeline cannot be forecast yet, the process should be quicker than a regular evaluation due to the time gained during the rolling review.

The review of the data is being carried out by the EMA’s Committee for Medicinal Products for Human Use (CHMP). The decision to start the rolling review is based on the interim analysis of efficacy and safety data from the Phase 3 COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial – Intent to Care Early) trial, which evaluated sotrovimab as monotherapy for the early treatment of COVID-19 in adults at high risk of hospitalisation. Results of the interim analysis, based on data from 583 randomised patients, demonstrated an 85% (p=0.002) reduction in hospitalisations over 24 hours or deaths in those receiving sotrovimab compared to placebo, the primary endpoint of the trial.

Separately, the CHMP is also reviewing sotrovimab under Article 5(3) of Regulation 726/2004 and is expected to provide EU-wide recommendations for national authorities who may take evidence-based decisions on the early use of the medicine, ahead of any formal Marketing Authorisation.

Sotrovimab is an investigational compound and has not been granted a marketing authorisation anywhere in the world.

An Emergency Use Authorization (EUA) application for sotrovimab has been submitted to the US Food and Drug Administration (FDA). Sotrovimab is also under review by other global regulators including Health Canada under the expedited Interim Order application pathway for COVID-19 drugs.

About the COMET-ICE Study Design

The multi-center, double-blind, placebo-controlled, Phase 3 COMET-ICE trial investigated sotrovimab in adults with mild or moderate COVID-19 at high risk of progression to severe disease.

This Phase 3 trial evaluated the safety and efficacy of a single IV infusion of sotrovimab (500 mg) or placebo in non-hospitalised participants globally. The efficacy interim analysis included 291 patients in the treatment arm and 292 patients in the placebo arm. Among those studied, 63% were Hispanic or Latinx and 7% were Black or African American. The primary efficacy endpoint was the proportion of patients who have progression of COVID-19 as defined by the need for hospitalisation for at least 24 hours or death within 29 days of randomization.

In March 2021, an Independent Data Monitoring Committee recommended that the COMET-ICE trial be stopped for enrolment due to evidence of efficacy and is continuing to follow study participants for 24 weeks. Additional results, including epidemiology and virology data, will be forthcoming once the trial is completed and will be published in a peer reviewed medical journal. In COMET-ICE, infusion- related reactions were reported at a low frequency (1%) in sotrovimab-treated patients and was comparable to the incidence in the placebo arm (1%). These infusion-related reactions occurring within 24 hours of study treatment included pyrexia, chills, dizziness, dyspnea, pruritus and rash, which were Grade 1 (mild) or Grade 2 (moderate) and no events consistent with antibody dependent enhancement (ADE) were observed.

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 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 quarter of 2021 in uninfected adults at high risk to determine whether IM-administered sotrovimab can prevent symptomatic infection.

Sotrovimab was also evaluated in the outpatient setting in BLAZE-4, a Phase 2 trial sponsored by Eli Lilly and Company, designed to assess the safety and efficacy of bamlanivimab (LY-CoV555) alone and bamlanivimab with other neutralizing antibodies, including sotrovimab, versus placebo in low-risk adults with mild to moderate COVID-19. An interim analysis found that bamlanivimab (700 mg) co-administered with sotrovimab (500 mg) demonstrated a 70% relative reduction of patients with persistently high viral load at day 7 compared to placebo, meeting the primary endpoint. The three companies are engaging with the FDA regarding the possible co-administration of bamlanivimab and sotrovimab for the treatment of COVID-19.

Additionally, sotrovimab, along with VIR-7832, is being evaluated in the Phase 1b/2a National Health Service-supported AGILE trial in adults with mild to moderate COVID-19. VIR-7832 is the second monoclonal antibody from the Vir–GSK collaboration to be investigated as a potential COVID-19 treatment.