Health Canada considering Evusheld for COVID-19 pre-exposure prophylaxis

The first product for pre-exposure prophylaxis of COVID-19 is under consideration for approval by Health Canada.1 AstraZeneca’s Evusheld is a combination of two long-acting monoclonal antibodies (tixagevimab copackaged with cilgavimab), administered concomitantly by intramuscular injection.2 The combination therapy recently received Emergency Use Authorization by the Food and Drug Administration (FDA) in the United States, where it is indicated for pre-exposure prophylaxis of COVID-19 in persons ≥ 12 years of age who weigh ≥ 40 kg and have moderate or severe immune compromise, or a history of severe allergy that prevents vaccination against COVID-19.2 Tixagevimab (AZD8895) and cilgavimab (AZD1061) are two human monoclonal antibodies derived from B-cells donated by convalescent patients after SARS-CoV-2 infection.3 They bind to portions of the SARS-CoV-2 spike protein, thereby preventing the virus from interacting with human ACE2 receptors. Both drugs have long half-lives—with mean half-lives of approximately 88 days for tixagevimab and 83 days for cilgavimab.2, 3 Emergency Use Authorization in the United States was based on results of the unpublished double-blind trial (PROVENT) in 5,172 adults who were not vaccinated against COVID-19. Trial participants were also at elevated risk because of their age (≥ 60 years), a comorbidity (e.g., obesity, COPD, immune compromise, history of severe/serious adverse reaction to any FDA-licensed vaccine), or their residential or occupational status. After a median follow-up of 83 days, symptomatic COVID-19 occurred in eight (0.2%) of subjects who received the antibodies and in 17 (1.0%) who received placebo (HR 0.23 [95% CI 0.10–0.54]).2 Read: Where will Nuvaxovid—the first protein subunit COVID-19 vaccine—fit in? Similar results were seen in a post-hoc analysis with a median follow-up of 6.5 months after receiving a single dose of each antibody (0.3% vs 1.8%; HR 0.17 [95% CI 0.09–0.34]). No severe or critical COVID-19 events occurred in the antibody group compared to five in the placebo group. Note that the Omicron variant was not prevalent during these clinical trials.2 In the PROVENT study, the most common adverse effects of the antibody combination were headache (6%) and fatigue (4%). In the post-hoc analysis of PROVENT, the incidence of serious cardiac adverse events (e.g., myocardial infarction, cardiac failure, arrhythmia) was higher in the antibody group than in the placebo group (0.6% vs 0.2%), and one person who received the antibodies died of a myocardial infarction. However, no clear temporal relationship was seen between antibody administration and these cardiac adverse events.2 The recommended dosage is 150 mg of each antibody administered as consecutive intramuscular injections into separate sites (preferably one injection in each gluteal muscle). Patients should be monitored for at least one hour after administration.2 Tixagevimab and cilgavimab can be given once every six months while SARS-CoV-2 is in circulation. The antibodies should not be used for treatment or post-exposure prophylaxis of COVID-19, or within two weeks after administration of a COVID-19 vaccine.2 Read: Ventilation still needed as part of CPR used in drowning victims In the United States, Evusheld is supplied in cartons containing one 150 mg/1.5 mL vial of tixagevimab and one 150 mg/1.5 mL vial of cilgavimab. The vials should be stored in the refrigerator before use.2 AstraZeneca Canada has announced the signing of an agreement with the Government of Canada to supply of 100,000 doses of Evusheld for the pre-exposure prophylaxis of COVID-19 in at-risk patients. The doses are expected to be delivered in 2022, provided that Evusheld receives regulatory approval from Health Canada.3 References 1. Government of Canada. Drug and vaccine authorizations for COVID-19: list of applications received. https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/authorization/applications.html#wb-auto-4 (accessed February 28, 2022). 2. Anon. Tixagevimab and cilgavimab (Evusheld) for pre-exposure prophylaxis of COVID-19. Med Lett Drugs Ther 2022;63:1-2. https://secure.medicalletter.org/w1641a (accessed February 28, 2022). 3. AstraZeneca Canada Inc. AstraZeneca to supply Canada with 100,000 doses of Evusheld, a long-acting antibody combination for the prevention of COVID-19. February 23, 2022. https://www.newswire.ca/news-releases/astrazeneca-to-supply-canada-with-100-000-doses-of-evusheld-a-long-acting-antibody-combination-for-the-prevention-of-covid-19-845874319.html (accessed February 28, 2022).

Health Canada considering Evusheld for COVID-19 pre-exposure prophylaxis

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