Sotrovimab Clinical, Safety, & Variant Information

Learn more about sotrovimab clinical and safety data. This page also contains information on viral variants based on in vitro data.

What’s on This Page

Clinical Data Results
Overall Safety Summary
Sotrovimab Variant Data (In Vitro)

Clinical Data Results
Overall Safety Summary
Sotrovimab Variant Data (In Vitro)

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

Clinical Data Results

COMET-ICE Study Design

The clinical data supporting this EUA are based on the analysis of the Phase 1/2/3 COMET-ICE trial (NCT #04545060). 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.

Baseline Characteristics

A total of 1,057 eligible subjects were randomized to receive a single 500-mg infusion of sotrovimab (n=528) or placebo (n=529) over 1 hour (Intent to Treat [ITT] population at Day 29). At baseline, the median age was 53 years (range: 17 to 96); 20% 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, 8% Black or African American, 4% Asian, 65% Hispanic or Latino. Fifty-nine percent of subjects received sotrovimab or placebo within 3 days of COVID-19 symptom onset and 41% within 4 to 5 days. The four most common pre-defined risk factors or comorbidities were obesity (63%), 55 years of age or older (47%), diabetes requiring medication (22%), and moderate-to-severe asthma (17%). 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 79% (adjusted relative risk reduction) in recipients of sotrovimab versus placebo. The tables below provide the results for the primary and key secondary endpoint of COMET-ICE.

Efficacy Results in Adults With Mild-to-Moderate COVID-19 at Day 29

	Sotrovimab n = 528	Placebo n = 529
Progression of COVID-19 (defined as hospitalization for >24 hours for acute management of any illness or death from any cause) (Day 29)^a
Proportion (n, %)	6 (1%)	30 (6%)
Adjusted Relative Risk Reduction (95% CI)	79% (50%, 91%)
All-cause mortality (up to Day 29)
Proportion (n, %)	0	2 (<1%)

The determination of primary efficacy was based on a planned interim analysis of 583 patients, which had similar findings to those seen in the full population above. The adjusted relative risk reduction was 85% with a 97.24% CI of (44%, 96%) and p-value = 0.002.

Within the subset of the ITT population who had a central laboratory confirmed, virologically quantifiable nasopharyngeal swab at Day 1 and Day 8 (n = 639), the mean decline from baseline in viral load at Day 8 was greater in subjects treated with sotrovimab (-2.610 log10 copies/mL) compared to that in subjects treated with placebo (-2.358); mean difference = -0.251, 95% CI: (-0.415, -0.087).

Overall Safety Summary

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 based on an analysis from 1,049 patients.

All patients received a single 500-mg infusion of sotrovimab (n=523) or placebo (n=526). 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.

Hypersensitivity adverse reactions have been observed in 2% of patients treated with sotrovimab and 1% with placebo in COMET-ICE.

Most Common Treatment-Emergent Adverse Events

In COMET-ICE, rash (1%) and diarrhea (2%) 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 choose an authorized therapeutic option with activity against circulating SARS-CoV-2 variants in their state. SARS-CoV-2 variant frequency data for states and jurisdictions can be accessed on the CDC website.¹

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

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	Country First Identified	Key Substitutions Tested	Fold Reduction in Susceptibility
Alpha
B.1.1.7	UK	N501Y^a	No change^b
Beta
B.1.351	South Africa	K417N + E484K + N501Y^c	No change^b
Gamma
P.1	Brazil	K417T + E484K + N501Y^d	No change^b
Epsilon
B.1.427/B.1.429	USA (California)	L452R^e	No change^b
Iota
B.1.526^f	USA (New York)	E484K^g	No change^b
Kappa
B.1.617.1	India	L452R + E484Q^h	No change^b
Delta
B.1.617.2	India	L452R + T478Kⁱ	No change^b
Delta [+K417N]
AY.1/AY.2^j	India	L452R + T478K + K417N^k	No change^b
Lambda
C.37	Peru	G75V, T76I, del246-252, L452Q, F490S, T859N^l	No change^b

Pseudotyped VSV-luc expressing variant spike protein was tested. The following changes from wild-type spike protein are found in the variant: del69-70, del144, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H.

No change: <5-fold reduction in susceptibility.

Pseudotyped VSV-luc expressing variant spike protein was tested. The following changes from wild-type spike protein are found in the variant: L18F, D80A, D215G, R246I, K417N, E484K, N501Y, A701V.

Pseudotyped VSV-luc expressing variant spike protein was tested. The following changes from wild-type spike protein are found in the variant: L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I, V1176F.

Pseudotyped VSV-luc expressing variant spike protein was tested. The following changes from wild-type spike protein are found in the variant: S13I, W152C, L452R, D614G.

Not all isolates of the New York lineage harbor the E484K substitution (as of February 2021).

Pseudotyped VSV-luc expressing variant spike protein was tested. The following changes from wild-type spike protein are found in the variant: L5F, T95I, D253G, E484K, D614G, A701V.

Pseudotyped VSV-luc expressing variant spike protein was tested. The following changes from wild-type spike protein are found in the variant: T95I, G142D, E154K, L452R, E484Q, D614G, P681R, Q1071H.

ⁱ

Pseudotyped VSV-luc expressing variant spike protein was tested. The following changes from wild-type spike protein are found in the variant: T19R, G142D, E156G, del157-158, L452R, T478K, D614G, P681R, D950N.

Commonly known as "Delta plus."

Pseudotyped VSV-luc expressing variant spike protein was tested. The following changes from wild-type spike protein are found in the variant: AY.1 T19R, T95I, G142D, E156G, del157-158, W258L, K417N, L452R, T478K, D614G, P681R, D950N; AY.2. T19R, V70F, G142D, E156G, del157-158, A222V, K417N, L452R, T478K, D614G, P681R, D950N.

Pseudotyped VSV-luc expressing variant spike protein was tested. The following changes from wild-type spike protein are found in the variant: G75V, T76I, del246-252, L452Q, F490S, T859N.

Authentic SARS-CoV-2 Neutralization Data for SARS-CoV-2 Variant Substitutions for Sotrovimab

Scroll right to view remainder of table.

SARS-CoV-2 Lineage	Country First Identified	Key Substitutions^a	Fold Reduction in Susceptibility
Alpha
B.1.1.7	UK	N501Y	No change^b
Beta
B.1.351	South Africa	K417N + E484K + N501Y	No change^b
Gamma
P.1	Brazil	K417T + E484K + N501Y	No change^b

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

No change: <5-fold reduction in susceptibility.

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.

Call GSK COVID Contact Center
1-866-GSK-COVID (866-475-2684) or
click here to request a follow-up.

GSK MedInfo

To learn more about COVID-19, visit the CDC and WHO websites.

AUTHORIZED USE

IMPORTANT SAFETY INFORMATION

AUTHORIZED USE & SAFETY INFO

AUTHORIZED USE

Sotrovimab is authorized for use under an Emergency Use Authorization (EUA) for the treatment of mild-to-moderate coronavirus disease 2019...[Continue Reading]

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Sotrovimab is contraindicated in patients who have a history of anaphylaxis to sotrovimab or to any of the excipients in the formulation....[Continue Reading]

Sotrovimab is authorized for use under an Emergency Use Authorization (EUA) 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...[Continue Reading]

AUTHORIZED USE

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).
Benefit of treatment with sotrovimab has not been observed in patients hospitalized due to COVID‑19. SARS-CoV-2 monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID‑19 requiring high flow oxygen or mechanical ventilation.

Sotrovimab is not FDA-approved and 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.

CONTRAINDICATIONS

Sotrovimab is contraindicated in patients who have a history of anaphylaxis to sotrovimab or to any of the excipients in the formulation.

WARNINGS AND PRECAUTIONS

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

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Sotrovimab is contraindicated in patients who have a history of anaphylaxis to sotrovimab or to any of the excipients in the formulation.

WARNINGS AND PRECAUTIONS

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

Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions

Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of sotrovimab. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care.

Infusion-related reactions, occurring during the infusion and up to 24 hours after the infusion, have been observed with administration of sotrovimab. These reactions may be severe or life threatening.

Signs and symptoms of infusion-related reactions may include: fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia (eg, atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, nausea, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, vaso-vagal reactions (eg, pre-syncope, syncope), dizziness and diaphoresis.

Consider slowing or stopping the infusion and administer appropriate medications and/or supportive care if an infusion-related reaction occurs.

Hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of SARS-CoV-2 monoclonal antibodies under Emergency Use Authorization.

Clinical Worsening After SARS-CoV-2 Monoclonal Antibody Administration

Clinical worsening of COVID‑19 after administration of SARS-CoV-2 monoclonal antibody treatment has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmia (eg, atrial fibrillation, tachycardia, bradycardia), fatigue, and altered mental status. Some of these events required hospitalization. It is not known if these events were related to SARS-CoV-2 monoclonal antibody use or were due to progression of COVID‑19.

Limitations of Benefit and Potential for Risk in Patients with Severe COVID‑19

Benefit of treatment with sotrovimab has not been observed in patients hospitalized due to COVID‑19. SARS-CoV-2 monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID‑19 requiring high flow oxygen or mechanical ventilation. Therefore, 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.

ADVERSE EVENTS

Hypersensitivity adverse reactions have been observed in 2% of patients treated with sotrovimab and 1% with placebo in COMET-ICE.

The most common treatment-emergent adverse events observed in the sotrovimab treatment group in COMET-ICE were rash (1%) and diarrhea (2%), 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.

Reporting Adverse Events:

The prescribing healthcare provider and/or the provider’s designee is/are responsible for mandatory reporting of all medication errors and serious adverse events potentially related to sotrovimab within 7 calendar days from the onset of the event. The reports should include unique identifiers and the words “Sotrovimab use for COVID-19 under Emergency Use Authorization (EUA)” in the description section of the report.

Submit adverse event reports to FDA MedWatch using one of the following methods:

Complete and submit the report online at http://www.fda.gov/medwatch/report.htm, or
Complete and submit a postage-paid FDA Form 3500 (https://www.fda.gov/media/76299/download) and return by: Mail (MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787), or by fax (1-800-FDA-0178), or Call 1-800-FDA-1088 to request a reporting form.

In addition, please provide a copy of all FDA MedWatch forms to: GlaxoSmithKline, Global Safety; Fax: 919-287-2902; Email: WW.GSKaereportingUS@gsk.com; Or call the GSK COVID Contact Center at 1-866-GSK-COVID (866-475-2684) to report adverse events.

USE IN SPECIFIC POPULATIONS

Pregnancy

There are insufficient data to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcome. Sotrovimab should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.

Lactation

There are no available data on the presence of sotrovimab in human milk, the effects on the breastfed infant, or the effects on milk production. Individuals with COVID-19 who are breastfeeding should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.

Reference: 1. Variants and genomic surveillance for SARS-CoV-2. Centers for Disease Control and Prevention website. Updated April 2, 2021. Accessed December 6, 2021. https://www.cdc.gov/coronavirus/2019-ncov/variants/index.html

To report SUSPECTED ADVERSE REACTIONS, contact GSK at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Trademarks are owned by or licensed to the GSK group of companies.

This is my caption