Regulatory Decision Summary for Moderna COVID-19 Vaccine

 

The purpose of this submission was to obtain the market authorization, under the Interim Order respecting the importation, sale and advertising of drugs for use in relation to COVID-19, for the Moderna COVID-19 Vaccine. To support the authorization of the Moderna COVID-19 vaccine, efficacy, immunogenicity and safety data from three ongoing clinical trials were provided, Study P101, a first-in-human Phase 1 study (FIH); Study P201, a Phase 2a dose confirmation study; and Study P301Phase 3 pivotal clinical trial.

Health Canada decision issued:

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

Date of decision:

2020-12-23

Indication (use):

Moderna COVID-19 Vaccine (COVID-19 mRNA Vaccine) is indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) in individuals 18 years of age and older.

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

The ongoing COVID-19 pandemic has a significant impact on public health. The availability of safe and effective vaccines will reduce the spread and severity of COVID-19 disease and reduce its social and economic consequences.

The vaccine efficacy of Moderna COVID-19 Vaccine was demonstrated in a Phase 3 randomized, placebo controlled study in adults ≥ 18 years of age (Study mRNA-1273-P301). The study is conducted in 99 sites across the United States, and is still ongoing. A total of 30,351 individuals were randomly assigned to receive two intramuscular injections of 100 µg of the vaccine (n=15,181) or placebo (n=15,170) separated by four weeks. Participants were stratified by age and health risk into one of three groups: 18 to <65 years of age and not at risk for progression to severe COVID-19; 18 to <65 years of age and at risk for progression to severe COVID-19; and ≥65 years of age. The proportion of participants 65 years of age and over is 24.7%.

Compared to placebo, vaccine efficacy was evaluated to be 94.1% (95% confidence interval (CI) 89.3%, 96.8%) in participants without prior evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection 2 weeks after the second dose of the vaccine. The vaccine efficacy in participants older than 65 years of age was 86.4% (95% CI: 61.4%, 95.5%). There were 30 cases of severe COVID-19 disease in the placebo group and 0 cases in the vaccine group.

All participants were monitored for safety. A total of 8,163 participants in the vaccine group and 8,111 in the placebo group were followed for at least 2 months after the second dose.

The most frequently reported adverse reactions (ARs) after any dose were: pain at the injection site (92.0%), fatigue (70.0%), headache (64.7%), myalgia (61.5%), and chills (45.4%). The majority of local and systemic adverse reactions were mild to moderate in severity and resolved within 2 to 3 days. ARs were more common in younger adults (18 to < 65 years) as compared to older adults (≥ 65 years). More ARs were reported following the second dose. The incidence and absolute number of serious adverse events in the 28 days after vaccination was comparable between Moderna COVID-19 Vaccine (0.5%) and placebo (0.6%) groups.

There were no important safety issues identified and no life-threatening adverse events (AEs) or deaths related to the vaccine. The AEs observed showed that the vaccine at 100 µg was safe and well-tolerated in participants and within demographic subgroups based on age, sex, and race/ethnicity.

One limitation of the data at this time is the lack of information on the long-term safety and efficacy of the vaccine. The identified limitations are managed through labelling and the Risk Management Plan. The Phase 3 Study is ongoing and will continue to collect information on the long-term safety and efficacy of the vaccine. Terms and conditions were imposed on the authorization to require monitoring of the long-term safety and efficacy of Moderna COVID-19 Vaccine.

A Risk Management Plan (RMP) was established for Moderna mRNA 1273 COVID-19 Vaccine. 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 safety profile of the product. This included providing information in the product monograph and identifying populations where more data is needed. The RMP will be updated to reflect additional safety information as this is collected. In addition to regulatory requirements for post-market monitoring and prioritized reporting of adverse events following immunization, monthly safety summary reports on the vaccine will be provided to Health Canada. Results related to safety and effectiveness from ongoing and planned studies will be submitted as they become available.

Manufacture of the Moderna COVID-19 vaccine consists of the production of the mRNA encoding the Spike protein for the SARS-CoV-2 virus, followed by the encapsulation of this mRNA into Lipid Nanoparticles. Evidence was provided to demonstrate that the vaccine is manufactured under Good Manufacturing Practices (GMP) at all manufacturing sites providing supply to Canada, and that in-process controls, process parameters, and quality control release tests have been established to monitor product quality throughout the process. The specifications used to evaluate key quality attributes and consistency of production were found acceptable. This information, together with the terms and conditions imposed on the authorization, support authorization under the Interim Order.

In conclusion, the data provided supports favorably the efficacy of the Moderna COVID-19 Vaccine as well as its safety. The efficacy of the vaccine was established to be 94.1%, the vaccine was well tolerated by participants and has no important safety concerns. The benefit to risk assessment for Moderna COVID-19 Vaccine is considered favorable.

Directions for use:

Moderna COVID-19 Vaccine should be administered intramuscularly, as two 0.5 mL doses, one month apart.

Moderna COVID-19 Vaccine is a suspension for intramuscular injection. A single dose is 0.5 mL.

For more information, refer to the Product Monograph for Moderna COVID-19 Vaccine.

Terms and Conditions:

Terms and conditions were imposed upon the authorization with respect to quality, clinical, labelling, and Risk Management Plan requirements.

For more information, refer to the Authorization Terms and Conditions for Moderna COVID-19 Vaccine.