Regulatory Decision Summary for SPIKEVAX

The information below summarizes the rationale for approval of the vaccine under the Food and Drug Regulations. Some of this information is already available in previous Summaries of Rationale for Approval that were published when the vaccine was authorized under the IO.

COVID-19 is a serious and potentially fatal or life-threatening human infection. Vaccination is an important way to protect against the disease and help stop the pandemic.

The efficacy of SPIKEVAX was demonstrated in a Phase 3 randomized, placebo controlled study in adults ≥ 18 years of age was conducted at 99 sites across the United States. 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 was 24.7%.

Compared to placebo, the vaccine efficacy (VE) was 94.1% (95% confidence interval [CI] 89.3% to 96.8%) in participants without prior evidence of SARS CoV-2 infection 2 weeks after the second dose of the vaccine. VE in participants older than 65 years of age was 86.4% (95% CI: 61.4% to 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.

Serious adverse events (SAE) were reported in 0.6% of participants who received SPIKEVAX and 0.6% of participants who received a placebo, from the first dose until 28 days following the last vaccination. SAEs were reported in 1% of participants who received SPIKEVAX and 1% of participants who received a placebo, from the first dose until the last observation.

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 the adults and within demographic subgroups based on age, sex, and race/ethnicity.

The safety, efficacy and immunogenicity of SPIKEVAX in adolescents 12 to 17 years of age was evaluated in an Phase 2/3, randomized, observer-blind, placebo-controlled clinical study (data cut-off date of May 8, 2021). A total of 3,732 adolescents 12 to 17 years of age were enrolled in the study and randomised 2:1 to receive 2 doses of the vaccine or placebo 28 days apart. Participants with known history of SARS-CoV-2 infection were excluded from the study.

Compared to placebo, the vaccine efficacy in participants with first COVID-19 occurrence from 14 days after Dose 2 was 100% (95% CI: 28.9% to 100%); there were 0 confirmed COVID-19 cases identified in the vaccine group (n=2,162) and 4 in the placebo group (n=1,073). The vaccine efficacy demonstrated in adolescents 12 to 17 years of age is consistent with that previously demonstrated in the adult population.

Safety data in adolescents involved 3,726 participants who received at least one dose of SPIKEVAX (n=2,486) or placebo (n=1,240). Of these, 1,360 adolescents (vaccine=942, placebo=418) were followed for at least 2 months after the second dose at the time of the analysis. The most frequently reported adverse reactions in adolescent subjects were pain at the injection site (97.2%), headache (78.4%), fatigue (75.2%), myalgia (54.3%), and chills (49.1%). They occurred within the first 1 or 2 days after any dose and persisted for a median of 1 to 3 days. They were reported more frequently in the vaccine group than in the placebo group.

During the clinical study, the incidence of serious adverse events was 0.2% in both groups. No SAEs were assessed by the investigators as related to the study vaccine. No deaths and no cases of multisystem inflammatory syndrome in children (MIS-C) were reported. No cases of myocarditis/pericarditis and Bells palsy were reported. No reports of anaphylactic reaction were assessed as related to the vaccine. No cases of severe COVID-19 were reported in the adolescents 12 to 17 years of age in the vaccine or the placebo groups.

Very rare cases of anaphylactic reactions and/or hypersensitivity reactions, myocarditis and/or pericarditis, or facial paralysis/Bells palsy following administration of the vaccine have been reported outside of the clinical trials with SPIKEVAX. An important limitation of the data is the lack of information on the long-term safety and effectiveness of the vaccine. The identified limitations are managed through labelling and the Risk Management Plan (RMP).

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 are 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.

In conclusion, based on the data provided, the risk-benefit profile of SPIKEVAX is considered favourable. The efficacy of the vaccine was established and the vaccine was well tolerated by participants. The sponsor will continue to collect and report on the safety and efficacy of the vaccine.

SPIKEVAX is therefore recommended for authorization under Food and Drug Regulations for drugs for use in relation to COVID-19 and 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 12 years of age and older.