Health professional risk communication

Casirivimab and Imdevimab – High Risk of Treatment Failure Due to Circulation of SARS-CoV-2 Omicron Variant

Last updated

Summary

Product
Casirivimab and Imdevimab
Issue
Health products - New safety information
COVID
What to do

See Key Messages below

Audience
Health professionals

Affected products

Casirivimab and imdevimab concentrate for infusion is available in cartons that contain either two single-use 6 mL vials or two single-use 20 mL vials per package.

Each carton contains 2 single-use vials per package:

  • DIN 02516691 (6 mL vial size)
    • 1 vial of  300 mg casirivimab / 2.5 mL (120 mg/mL) and
    • 1 vial of 300 mg imdevimab / 2.5 mL (120 mg/mL)

OR

  •  DIN 02516705 (20 mL vial size)
    • 1 vial of 1332 mg casirivimab / 11.1 mL (120 mg/mL) and
    • 1 vial of 1332 mg imdevimab / 11.1 mL (120 mg/mL) 

Issue

There is a high risk of treatment failure with the casirivimab and imdevimab combination based on analysis of neutralization activity against selected mutations of the SARS-CoV-2 Omicron variant. The Canadian Product Monograph for casirivimab and imdevimab will be updated to include new information about this Variant of Concern (VoC).

 

Audience

Healthcare professionals including infectious disease physicians, internal medicine physicians, pharmacists, hospital pharmacy departments, chiefs of medicine in hospitals, intensive care unit and emergency room physicians.

 

Key messages​​​​

  • There is significantly reduced neutralization potency and a high risk of treatment failure with the casirivimab and imdevimab combination against the SARS-CoV-2 B.1.1.529/BA.1 variant (Omicron).
  • Healthcare professionals are advised of the following:
    • Casirivimab and imdevimab should only be considered for patients where the Omicron variant has been ruled out.
    • Where the Omicron variant cannot be ruled out, other therapies should be considered.
  • The Canadian Product Monograph for casirivimab and imdevimab, which is available in French and English on Health Canada’s Drug Product Database, at www.cas-imd.ca or www.rochecanada.com, will be updated to include new information concerning the Omicron variant.

 

Background

Casirivimab and imdevimab, to be administered together, are indicated for the treatment of mild to moderate coronavirus disease 2019 (COVID-19), confirmed by direct SARS-CoV-2 viral testing, in adults and adolescents (12 years of age and older weighing at least 40 kg) who are at high risk for progressing to hospitalization and/or death.

 

This combination therapy 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.
     

Regeneron and Roche, in partnership, monitor and test the activity of casirivimab and imdevimab against variants under surveillance. Initial data from in vitro pseudovirus neutralization assays demonstrated significantly reduced neutralization potency for casirivimab and imdevimab against the SARS-CoV-2 Omicron variant (see Table 1). Neutralization activity against other VoCs and variants under surveillance is outlined in Table 1 for the casirivimab and imdevimab combination.  

 

Table 1: Pseudotyped Virus-Like Particle Neutralization Data for Variants of Concern and Variants Under Surveillance with the Casirivimab and Imdevimab Combination

Lineage with Spike Protein Substitutions

WHO

Nomenclature

Key Substitutions Tested

Reduced Susceptibility to Casirivimab and Imdevimab Together 

B.1.1.7

Alpha

Full S protein

no change

B.1.351

Beta

Full S protein

no change

P.1

Gamma

Full S protein

no change

B.1.427/B.1.429

Epsilon

L452R

no change

B.1.526

Iota

E484K

no change

B.1.617.1/

B.1.617.3

Kappa

L452R+E484Q

no change

B.1.617.2

Delta

L452R+T478K

no change

B.1.621

Mu

R346K+E484K+N501Y

no change

B.1.1.529/BA.1

Omicron

Full S protein

>1013-fold

 

Information for healthcare professionals

There is a high risk of treatment failure with the casirivimab and imdevimab combination against the SARS-CoV-2 Omicron variant.

Healthcare professionals are advised of the following:

  • Casirivimab and imdevimab should only be considered for patients where the Omicron variant has been ruled out.
  • Where the Omicron variant cannot be ruled out, other therapies should be considered.

The Canadian Product Monograph for casirivimab and imdevimab, available in French and English on Health Canada’s Drug Product Database, at www.cas-imd.ca or www.rochecanada.com, will be updated to include new information concerning the Omicron variant.

 

 

Action taken by Health Canada

Health Canada has worked with Hoffmann-La Roche Limited to prepare this alert for casirivimab and imdevimab. Health Canada is communicating this important safety information to healthcare professionals and Canadians via the Recalls and Safety Alerts Database on the Healthy Canadians Website. This communication will be further distributed through the MedEffect™ e-Notice email notification system, as well as through social media channels, including LinkedIn and Twitter.

 

 

Report health or safety concerns

Managing marketed health product-related side effects depends on healthcare professionals and consumers reporting them. Any side effects in patients receiving casirivimab and imdevimab should be reported to Hoffmann-La Roche Limited, or to Health Canada.

Hoffmann-La Roche Limited

Drug Safety Department

7070 Mississauga Road

Mississauga, Ontario, L5N 5M8

Toll free: 1-888-762-4388

Fax: 905-542-5864

E-mail: mississauga.drug_safety@roche.com

To correct your mailing address or fax number, contact Hoffmann-La Roche Limited.

You can report any suspected adverse reactions associated with the use of health products to Health Canada by:

  • Calling toll-free at 1-866-234-2345; or
  • Visiting MedEffect Canada's Web page on Adverse Reaction Reporting for information on how to report online, by mail or by fax.

For other health product inquiries related to this communication, contact Health Canada at:

Biologic and Radiopharmaceutical Drugs Directorate

E-mail: brdd.dgo.enquiries@hc-sc.gc.ca

 

 

Original signed by

Loredana Regep, MD

Vice President, Medical & Regulatory Affairs

Hoffmann-La Roche Limited

 

Additional information

Details
Original published date:
Alert / recall type
Health professional risk communication
Category
Health products - Biologic or vaccine
Companies
Published by
Health Canada
Audience
Health professionals
Identification number
RA-63799