Regulatory Decision Summary for Evusheld

Authorization of Evusheld was based on a phase 3, randomized, double-blind, placebo-controlled study of a single dose of 300 mg Evusheld for the prevention of COVID-19 in adults (≥ 18 years) without prior history of COVID-19 and who had not received COVID-19 vaccination. The study demonstrated a statistically significant reduction in the percentage of participants who developed symptomatic laboratory-confirmed COVID-19 with Evusheld (0.2%, 8/3441) compared to placebo (1.0%, 17/1731).

The clinical trial for Evusheld to support authorization was conducted prior to the emergence of Omicron subvariants. Laboratory studies provided evidence that Evusheld is expected to retain neutralizing activity against BA.2. However, the neutralizing activity of Evusheld against BA.1 and BA.1.1 was reduced. Due to this reduced activity, a 600 mg dose should be considered in regions where BA.1 and BA.1.1 strains are circulating.

The safety of a single dose of 300 mg and 600 mg Evusheld by intramuscular injection was acceptable. Adverse reactions associated with Evusheld included hypersensitivity, injection site and anaphylactic reactions. These reactions were generally mild and reported in a small number of participants. While infrequent overall, a small increase in serious cardiac disorders (including myocardial infarction and cardiac failure) and thromboembolic events occurred in participants who received Evusheld compared to placebo. Most participants with these events had risk factors for cardiac disease or a history of cardiovascular disease prior to receiving Evusheld. A relationship between Evusheld and these events has not been established.

A Core Risk Management Plan (RMP) and a Canadian RMP Addendum were included in the submission for Evusheld. The RMP is designed to describe known and potential safety issues, to present the monitoring plan and when needed, to describe measures that will be put in place to minimize risks associated with the product. Upon review, the RMP was considered to be acceptable and identified appropriate monitoring (pharmacovigilance) activities and risk minimization measures based on the known safety profile of Evusheld. This included providing information in the product monograph and identifying populations where more data are needed. The RMP will be updated to reflect additional safety information as it is collected. In addition to regulatory requirements for post-market monitoring semi annual safety summary reports are required to be submitted to Health Canada.

The safety and efficacy has not been established in pregnant women and will be collected post marketing through a pregnancy registry. The identified limitations are managed through labelling and the Risk Management Plan. Results from ongoing and planned studies related to safety and effectiveness of the product will be submitted as they become available.

Given the unmet need in the context of the COVID-19 pandemic, Health Canada considers the potential benefits to outweigh the potential risks for Evusheld when used as per the Product Monograph directions.

Refer to the Product Monograph for further details on the benefits and risks of Evusheld.

The authorization of Evusheld is associated with Terms and Conditions that need to be met by the sponsor to manage uncertainties or mitigate risks.