EVUSHELD (tixagevimab and cilgavimab for injection) - Risk of Prophylaxis or Treatment Failure due to Antiviral Resistance

EVUSHELD (tixagevimab and cilgavimab for injection) may not be effective against certain SARS-CoV-2 Omicron subvariants.

Audience

Healthcare professionals including physicians, pharmacists, nursing staff and public health officials.

Key Messages

• EVUSHELD (tixagevimab and cilgavimab for injection) may not be effective against certain SARS-CoV-2 Omicron subvariants when used as a prophylaxis or treatment for COVID-19.
• Healthcare professionals are advised to:
  • Consider local epidemiology and individual exposure to circulating SARS-CoV-2 viral variants when making decisions regarding the use of EVUSHELD.
  • Inform patients who receive EVUSHELD about the potential for a lack of effectiveness against certain SARS-CoV-2 viral variants. Instruct patients to seek medical advice if signs or symptoms of COVID-19 occur, persist or worsen.
  • Refer to the EVUSHELD Canadian Product Monograph (CPM), in conjunction with the literature and local guidelines, for information regarding specific variants and antiviral resistance.

• The CPM for EVUSHELD has been updated with new information about the risk of prophylaxis or treatment failure due to antiviral resistance, including neutralization data on SARS-CoV-2 Omicron subvariants. The CPM is available in French and English on Health Canada’s Drug Product Database, at astrazeneca.ca, or by scanning the QR code on the global English-only carton label to visit www.laab.azcovid-19.com.
• For information on current variants of concern in Canada, visit the Government of Canada’s COVID-19 epidemiology update website.

Background information

EVUSHELD is indicated for:

• The pre-exposure prophylaxis of coronavirus disease 2019 (COVID-19) in adults and adolescents (≥12 years of age weighing at least 40 kg), who have not had a known recent exposure to an individual infected with SARS-CoV-2 and:
  • Who are immune compromised and unlikely to mount an adequate immune response to COVID‐19 vaccination or
  • For whom COVID-19 vaccination is not recommended.

       Pre-exposure prophylaxis with EVUSHELD is not a substitute for vaccination in individuals for whom COVID-19

       vaccination is recommended.

• The treatment of mild to moderate COVID-19 in adults and adolescents (≥12 years of age weighing at least 40 kg).

Circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies, such as EVUSHELD. The EVUSHELD Canadian Product Monograph (CPM) has been updated to include new information about the risk of prophylaxis or treatment failure due to antiviral resistance. Neutralization data for the following SARS-CoV-2 Omicron subvariants have also been added to the CPM: Omicron BA.2.12.1, BA.2.75, BA.3, BA.4, BA.4.6, and BA.5. See Table 1 (below) for a summary of this updated data. Refer to the CPM (Section 15: Microbiology, Table 7) for complete information.

Table 1: Updated Evusheld Neutralization Data for SARS-CoV-2 Omicron Subvariants

ND: not determined 

*Pseudovirus: An engineered virus expressing the SARS-CoV-2 spike protein with amino acid sequences specific to the subvariant, used as a surrogate to assess the effectiveness of EVUSHELD against the relevant subvariant spike protein.

Information for healthcare professionals

Decisions regarding the use of EVUSHELD should take into consideration what is known about the characteristics of the circulating SARS-CoV-2 viral variants, including geographical prevalence and individual exposure to variants.

Discuss the risk of breakthrough infections with patients who receive EVUSHELD as a prophylaxis, and instruct patients to seek medical advice if signs or symptoms of COVID-19 occur.

Discuss the risk of treatment failure with patients who receive EVUSHELD as a treatment, and advise patients to seek medical advice if signs or symptoms of  COVID-19 persist or worsen.

The CPM for EVUSHELD, which is available in French and English on Health Canada’s Drug Product Database, at astrazeneca.ca, or by scanning the QR code on the global English-only carton label to visit www.laab.azcovid-19.com, has been updated with new information about the risk of prophylaxis or treatment failure due to antiviral resistance, including neutralization data on SARS-CoV-2 Omicron subvariants. Healthcare professionals should routinely review the antiviral resistance information in the EVUSHELD CPM (see Section 15: Microbiology, Table 7), in conjunction with literature and local guidelines, for information regarding specific variants and resistance. This information will continue to be updated as new evidence emerges.

For information on current variants of concern in Canada, visit the Government of Canada’s COVID-19 epidemiology update website.

Action taken by Health Canada

Health Canada has worked with AstraZeneca Canada Inc. to prepare this alert for EVUSHELD. 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 serious or unexpected side effects in patients receiving EVUSHELD should be reported to AstraZeneca Canada Inc. or Health Canada.

AstraZeneca Canada Inc.

1004 Middlegate Road, Suite 5000

Mississauga

Ontario L4Y 1M4

For any medical questions related to EVUSHELD, contact AstraZeneca Canada Inc. Medical Information at 1-800-668-6000 or via https://contactazmedical.astrazeneca.com.

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

Alex Romanovschi, MD

Vice President, Scientific Affairs

AstraZeneca Canada Inc.