Regulatory Decision Summary for Spikevax Bivalent (Original/Omicron BA.4/5)

Authorization of the Spikevax Bivalent™ (Original / Omicron BA.4/5) booster dose was based on the safety data obtained in clinical studies using the Spikevax Bivalent™ (Original / Omicron BA.1) and Spikevax ™ original vaccines as booster doses. In addition, the efficacy of Spikevax ™ (Original / Omicron BA.4/5) was inferred from the immunogenicity of a Spikevax Bivalent™ (Original / Omicron BA.1) vaccine.

Spikevax Bivalent™ (Original / Omicron BA.1) vaccine:

Eligible, 814 individuals (male or female), over 18 years of age were included in the study, a total of 437 received the Spikevax Bivalent™ and 377 the comparator vaccine Spikevax ™. The immune responses were evaluated in these two groups against the Original SARS-CoV-2 virus or against the Omicron BA.1 virus. The results presented indicate that the new Spikevax Bivalent™ (Original / Omicron BA.1) vaccine induces similar responses to the Original virus and significantly higher responses to the Omicron BA.1 virus when compared to the Spikevax ™ approved vaccine. Overall, the findings indicate that the Spikevax Bivalent™ (Original / Omicron BA.1) provides better immune response to the Omicron BA.1.

At the time of analysis, participants were followed-up for safety for approximately 6 weeks after receiving the booster. Safety and immune response data from 3-months and 6-months of follow-up will be provided to Health Canada when available and were requested as part of the Terms and Conditions required for marketing authorization. The frequency and severity of the solicited Adverse Reactions (ARs) was similar between the two groups; the most common local solicited ARs (≥10%) were pain at the injection site (77.9% and 77.2%) and axillary swelling (17.1% and 19.6%) in the Spikevax Bivalent™ (Original / Omicron BA.1) and Spikevax ™ groups, respectively. The commonest (≥10%) solicited systemic ARs were fatigue (54.9% and 51.4%), headache (43.9% and 41.1%), myalgia (39.6% and 38.6%), arthralgia (31.1% and 31.7%), chills (23.8% and 21.1%) and nausea/vomiting (10.3% and 10.0%) in the Spikevax Bivalent™ (Original / Omicron BA.1) and Spikevax ™ groups, respectively.

No new safety concerns have been identified in studies when compared to the currently approved Spikevax mRNA vaccine. No deaths or Adverse Events of Special Interest (AESI) including cases of myocarditis or pericarditis occurred. Any safety concerns remain as those captured in the Spikevax original label.

Spikevax ™ (original approved vaccine):

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 pikevax ™ 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.

A Core Risk Management Plan (RMP) and a Canadian RMP Addendum were included in the submission for Spikevax Bivalent (Original / Omicron BA.4 – BA.5). The RMP is designed to describe known and potential safety issues, to present the monitoring plan and hen 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 Spikevax (original) and Spikevax Bivalent (Original / Omicron BA.1). 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 summary safety 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.

Conclusion:

Based on the totality of the information, the benefit-risk profile for a 50 µg booster dose of Spikevax Bivalent™ (Original / Omicron BA.4/5) is considered favourable in individuals 18 years of age or older. The Sponsor will provide Health Canada the safety and mmunogenicity data of the ongoing Spikevax Bivalent™ (Original / Omicron BA.4/5) clinical studies (see Terms and Conditions).

For further details about Spikevax Bivalent (Original/Omicron BA.4/5), please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.

For more information on Health Canada's decision, please view the Summary Basis of Decision.