Regulatory Decision Summary for Pr Sotrovimab

 

Health Canada decision issued:

Sotrovimab was authorized for use in relation to the COVID-19 pandemic, in accordance with section 5 of the Interim Order Respecting the Importation, Sale and Advertising of Drugs for Use in Relation to COVID-19.

Date of decision:

2021-07-30

Indication (use):

The following is the indication for Sotrovimab for use in relation to COVID-19: Sotrovimab is 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.

Health Canada analysis of known and potential benefits and known and potential risks:

Authorization of sotrovimab under the COVID-19 Interim Order is based on analyses of a randomized, placebo-controlled, clinical study of sotrovimab administered to outpatients diagnosed with mild to moderate COVID-19 illness. The study determined the efficacy of sotrovimab in reducing the number of hospitalizations due to COVID-19 and/or all-cause death in patients who were considered to be at high-risk of hospitalization due to progression of COVID-19. A statistically significant reduction in the number of hospitalizations and/or deaths among treated patients compared to those who received placebo was demonstrated.

The safety of a single dose of 500 mg sotrovimab was acceptable. The rates of adverse events (AEs) and serious AEs were lower in patients who received sotrovimab compared to those who received placebo. The most important adverse reactions associated with sotrovimab treatment are infusion-related reactions, hypersensitivity reactions and anaphylactic reactions. These types of reactions are of concern for monoclonal antibodies in general, but were observed rarely in all phases of the ongoing clinical study.

Laboratory evidence showed that sotrovimab can neutralize pseudoviruses (virus-like material that can be safely used in research), and in some cases, authentic SARS-CoV-2 viruses carrying important SARS-CoV-2 spike protein variants. The sponsor will provide regular updates to Health Canada regarding the activity of sotrovimab against additional variants of concern and/or variants of interest as the data become available. Refer to the Product Monograph for further details.

The inclusion of high-risk adolescents who weigh at least 40 kg in the indication is based on extrapolation of the efficacy and safety findings in adult patients. Health care professionals can prescribe sotrovimab to high-risk adolescents on a case by case basis.

A Core (global) Risk Management Plan (RMP) for sotrovimab was submitted to Health Canada. The RMP is designed to describe known and potential safety issues, to present the monitoring scheme and, when needed, to describe measures that will be put in place to minimize risks associated with the product. The RMP for sotrovimab includes information about the important identified risks of infusion-related reactions including serious hypersensitivity reactions and anaphylaxis. In addition, the sponsor will be closely monitoring the important potential risks of Immunogenicity and Antibody Dependent Enhancement. The RMP also identified a few areas of missing information (limited/no clinical data available): "use in children under age 12", "use in pregnant and lactating women" and "long-term safety". Upon review, Health Canada recommended the addition of “treatment failure due to antiviral resistance from SARS-CoV-2 variants” as missing information to the RMP.

Overall, the RMP was considered to be acceptable as it identified appropriate monitoring (pharmacovigilance) activities and risk minimization measures based on the safety profile of the product. The identified limitations with respect to the areas of missing information are managed through labelling and will continue to be investigated through ongoing and planned studies. In addition, post-authorization commitments include the submission of monthly safety summary reports to Health Canada throughout the duration of the IO. These monthly reports will include information related to special populations (e.g., pregnant women).

Given the emergency context of the COVID-19 pandemic, an authorization under the COVID-19 Interim Order is recommended, with the following indication: Sotrovimab is 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.

The authorization of sotrovimab is associated with Terms and Conditions that need to be met by the sponsor to ensure the continued quality, safety and efficacy of the product. The safety of sotrovimab in pediatric patients will be further assessed in ongoing and planned clinical studies, with a requirement for the submission of these studies to Health Canada.

For further information on this and other authorizations, please refer to Health Canada’s COVID-19 vaccines and treatments portal at https://covid-vaccine.canada.ca/.

Directions for use:

Sotrovimab is administered as a single intravenous infusion over 1 hour. The recommended dose is 500 mg sotrovimab. Patients should be monitored for 1 hour after infusion.

For more information, refer to the Product Monograph for sotrovimab.

Terms and Conditions:

Terms and conditions were imposed upon the authorization.