Casirivimab and imdevimab – high risk of treatment failure due to circulation of sars-cov-2 omicron variant

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

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Brand: Casirivimab And Imdevimab.