Sotrovimab Clinical, Safety, & Variant Information

Learn more about an interim analysis of sotrovimab clinical and safety data. This page also contains information on viral variants based on in vitro data, separate from the interim analysis.

For more information, please access the Detailed Guide for the Use of Sotrovimab or contact 1-866-GSK-COVID (866-475-2684).

Clinical Data Interim Results

COMET-ICE Study Design

Clinical data supporting this EUA are based on an interim analysis from the Phase 1/2/3 COMET-ICE trial (NCT #04545060) that occurred after 583 randomized subjects had the opportunity to complete at least Day 29 of the trial. COMET-ICE is an ongoing, randomized, double-blind, placebo-controlled trial studying sotrovimab for the treatment of subjects with mild-to-moderate COVID-19 (subjects with COVID-19 symptoms who are not hospitalized). Eligible subjects were 18 years of age and older with at least one of the following comorbidities: diabetes, obesity (BMI >30), chronic kidney disease, congestive heart failure, chronic obstructive pulmonary disease, or moderate to severe asthma, or were 55 years of age and older regardless of comorbidities. The study included symptomatic patients with SARS-CoV-2 infection as confirmed by local laboratory tests and/or point of care tests and symptom onset within 5 days of enrollment. Subjects with severe COVID-19 requiring supplemental oxygen or hospitalization and severely immunocompromised patients were excluded from the trial. Subjects were treated with a single 500-mg infusion of sotrovimab (n=291) or placebo (n=292) over 1 hour (Intent to Treat [ITT] population at interim analysis 1). 

 

Baseline Characteristics

The median age was 53 years (range: 18 to 96); 22% of subjects were 65 years of age or older and 11% were over 70 years of age; 46% of subjects were male; 87% were White, 7% Black or African American, 6% Asian and 63% Hispanic or Latino. Fifty-eight percent of subjects received sotrovimab or placebo within 3 days of COVID-19 symptom onset and 42% within 4 to 5 days. The 3 most common predefined risk factors or comorbidities were obesity (63%), 55 years of age or older (47%), and diabetes requiring medication (23%). Overall, baseline demographic and disease characteristics were well balanced between the treatment arms. 

 

Primary and Key Secondary Endpoints

The primary endpoint, progression of COVID-19 at Day 29, was reduced by 85% (adjusted relative risk reduction) in recipients of sotrovimab versus placebo (P=0.002). The table below provides the results of the primary endpoint and a key secondary endpoint of COMET-ICE.

 

Interim Efficacy Results in Adults With Mild-to-Moderate COVID-19

 

Sotrovimab

n=291

Placebo

n=292

Progression of COVID-19 (defined as hospitalization for >24 hours for acute management of any illness or death from any cause) (Day 29)

Proportion (n, %)

3 (1%)

21 (7%)

Adjusted Relative Risk Reduction (97.24% CI)

85%

(44%, 96%)

P-value

0.002

All-cause mortality (up to Day 29)

Proportion (n, %)

0

1 (<1%)

 

Analysis of change from baseline in viral load in COMET-ICE is not yet possible because data are not available in the majority of trial participants.

Overall Safety Summary (Interim Analysis)

The ongoing Phase 1/2/3 double-blind, placebo-controlled, randomized study enrolled 1,057 non-hospitalized patients with COVID-19 (COMET-ICE). The safety of sotrovimab is primarily based on an interim analysis from 868 patients through Day 15.

 

All patients received a single 500-mg infusion of sotrovimab (n=430) or placebo (n=438). Two patients experienced treatment interruptions due to infusion site extravasation; infusion was completed for each.

 

Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions

Infusion-related reactions, including immediate hypersensitivity reactions, have been observed in 1% of patients treated with sotrovimab and 1% of patients treated with placebo in COMET-ICE. Reported events that started within 24 hours of study treatment were pyrexia, chills, dizziness, dyspnea, pruritus, rash, and infusion-related reactions; all events were Grade 1 (mild) or Grade 2 (moderate).


One case of anaphylaxis was reported following sotrovimab infusion in a study in hospitalized patients; the infusion was immediately discontinued, and the patient received epinephrine. The event resolved but recurred within 2 hours; the patient received another dose of epinephrine and improved with no additional reactions. Other serious infusion-related reactions (including immediate hypersensitivity reactions) reported following sotrovimab infusion in the hospitalized study included Grade 3 (serious) or Grade 4 (life-threatening) bronchospasm and shortness of breath. These events were also reported following infusion of placebo. Sotrovimab is not authorized for use in patients hospitalized due to COVID-19.

 

Most Common Treatment-Emergent Adverse Events

In COMET-ICE, rash (2%) and diarrhea (1%) were observed in the sotrovimab group, 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.

 

There are limited clinical data available for sotrovimab. Serious and unexpected adverse events may occur that have not been previously reported with use of sotrovimab.

Sotrovimab Variant Data (In Vitro Data)

In vitro data indicate sotrovimab retains activity against expressing the spike protein substitution(s) identified in the below COVID-19 variants.

 

There is a potential risk of treatment failure due to the development of viral variants that are resistant to sotrovimab. Prescribing healthcare providers should consider the prevalence of SARS-CoV-2 variants in their area, where data are available, when considering treatment options.

 

It is not known how these data correlate with clinical outcomes.

 

Authentic SARS-CoV-2 and Pseudotyped Virus-Like Particle Neutralization Data for SARS-CoV-2 Variant Substitutions With Sotrovimab

Scroll right to view remainder of table.

Lineage With Spike Protein Substitution

Key Substitutions Testeda

Fold Reduction in Susceptibility (Pseudotyped VLP)

Fold Reduction in Susceptibility

(Authentic Virus)

B.1.1.7 (UK origin)

N501Y

No changeb

No changeb

B.1.351 (South Africa origin)

K417N + E484K + N501Y

No changeb

No changeb

P.1 (Brazil origin)

K417T + E484K + N501Y

No changeb

No changeb

B.1.427/B.1.429 (California origin)

L452R

No changeb

ndd

B.1.526 (New York origin)c

E484K

No changeb

ndd

B.1.617 (India origin)

L452R + E484Q

No changeb

ndd

aFor variants with more than 1 substitution of concern, only the one(s) with the greatest impact on activity is (are) listed.

bNo change: <5-fold reduction in susceptibility.

cNot all isolates of the New York lineage harbor the E484K substitution (as of February 2021).

dNot determined.

 

Healthcare providers should review the Antiviral Resistance information in Section 15 of the Fact Sheet for Healthcare Providers for details regarding specific variants and resistance, and refer to the CDC website as well as information from state and local health authorities regarding reports of viral variants of importance in their region to guide treatment decisions.

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