Regulatory Decision Summary for Comirnaty Original & Omicron BA.4/BA.5

Authorization of the Comirnaty^® Original & Omicron BA.4/BA.5 booster dose was based on the safety data obtained in clinical studies using the Comirnaty Original / Omicron BA.1 and Comirnaty Original vaccines as booster doses. In addition, the efficacy of Comirnay Original & Omicron BA.4/5 was inferred from the immunogenicity of a Comirnaty Original / Omicron BA.1 vaccine

Comirnaty^® Original / Omicron BA.1

Eligible adults over 55 years of age (610 individuals both male and female) were included in the study, a total of 305 individuals received the Comirnaty^® Original / Omicron BA.1 and 305 individuals received the comparator vaccine Comirnaty^® Original. 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 Comirnaty^® 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 Comirnaty^® Original approved vaccine.

Overall, the findings indicate that the Comirnaty^® Original / Omicron BA.1 provides better immune response to the Omicron BA.1. Planned post-market studies are expected to provide additional validation of the immune response.

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; local and systemic ARs within the first 7 days following vaccine administration, in all study arms with 61.1% and 59.5% of subjects experiencing any local ARs and 56% and 60.5% of subjects experiencing any systemic ARs in the Comirnaty^® Original or Comirnaty^® Bivalent Original / BA.1, respectively. The most common solicited local ARs were pain at injection site (60.1% and 58.1%) Comirnaty^® Original or Comirnaty^® Bivalent Original / BA.1, respectively, followed by redness and swelling. The most common solicited systemic ARs was fatigue (45.3% and 49.2%) Comirnaty^® Original or Comirnaty Bivalent Original / BA.1, respectively, followed by headache, chills and muscle and joint pain. Most local and systemic events were mild or moderate in severity with a median onset of 2 to 3 days; and most resolved within a median duration of 1 to 2 days after onset.

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

Comirnaty^® Original

The safety and efficacy of Comirnaty^® Original were evaluated in a multicenter, multinational, randomized, placebo-controlled, observer-blind study. A total of 44,047 in the Phase 3 study were 16 years of age or older and 2,260 participants were 12 to 15 years of age. A total of 8,018 participants were 65 years of age and older.

In the primary analysis (data cut-off date November 14, 2020), the vaccine efficacy against COVID-19 was 95% in participants 16 years of age and older without evidence of a prior infection with SARS-CoV-2 at 7 days after Dose 2. In a subgroup analysis of adolescents 12 to 15 years of age, the vaccine efficacy was 100%.

An updated analysis (data cut-off dated March 13, 2021) showed a vaccine efficacy of 91.3% in participants 16 years of age and older without evidence of prior infection with SARS-CoV-2 at 7 days after Dose 2, based on COVID-19 cases accrued 6 months in a blinded placebo-controlled follow-up. The vaccine efficacy was 94.5% in participants 65 years of age and older.

The vaccine efficacy against severe COVID-19 was 95.3% in participants 16 years of age and older, with 1 case in the vaccine group and 21 cases in the placebo groups. No severe COVID-19 cases were reported in adolescents 12 to 15 years of age in the clinical study.

For the safety evaluation a total of 25,651 (58.2%) participants 16 years of age and older were followed for up for 4 months after receiving a second dose; 3,082 (7.0%) were followed up for 6 months; 1,308 adolescents were followed for 2 months (data cut-off date March 13, 2021). The most common adverse reactions in participants 16 years of age and older after any dose included injection site pain (84.3%), fatigue (64.7%), headache (57.1%), muscle pain (40.2%), chills (34.7%), joint pain (25.0%), fever (15.2%), injection site swelling (11.1%), and injection site redness (9.9%).

Adverse reactions in adolescents 12 to 15 years of age included pain at the injection site (90.5%), fatigue (77.5%), headache (75.5%), chills (49.2%), muscle pain (42.2%), fever (24.3%), joint pain (20.2%), injection site swelling (9.2%), injection site redness (8.6%), lymphadenopathy (0.8%), and nausea (0.4%), based on the assessment of 1,308 adolescents 12 to 15 years of age who have been followed for at least 2 months after the second dose.

Both solicited local and systemic adverse reactions were more commonly reported by participants in the vaccine group than in the placebo group, and the adverse reactions generally increased after Dose 2. Adverse reactions were usually mild or moderate in intensity and resolved within a few days after vaccination.

For the unsolicited adverse events in participants 16 years of age and older, lymphadenopathy (swelling of lymph nodes) was reported in 0.4% of participants (87 in the vaccine group and 8 the placebo group) which is plausibly related to vaccination. Bell's palsy (facial paralysis) was reported by four participants in the vaccine group and two in the placebo group. Serious adverse events were reported by 165 (1.8%) Comirnaty^® Original recipients and 151 (1.7%) placebo recipients who received at least 1 dose of vaccine or placebo. Pericarditis (swelling of tissue surrounding the heart) was reported for one participant in the vaccine group, and no case was reported in the placebo group.

There were no notable patterns or numerical imbalances between treatment groups for specific categories of serious adverse events reported during the blinded placebo-controlled follow-up period of the study in adolescents 12 to 15 years of age, with the safety profile in these adolescents being comparable to that found in young adults 16 to 25 years of age. No deaths related to the vaccine were reported in the study. No cases of thrombotic events, myocarditis, erythema multiform, kidney inflammation or anaphylactic reaction following administration of the vaccine were reported in clinical trials.

Very rare cases of anaphylactic reactions and/or hypersensitivity reactions, myocarditis and/or pericarditis, or facial paralysis/Bell's palsy following administration of the vaccine have been reported outside of the clinical trials with Comirnaty^® Original. 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).

A Core Risk Management Plan (RMP) and a Canadian RMP Addendum were included in the submission for Comirnaty^® Original & Omicron BA.4/BA.5. 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 Comirnaty^® (original) and Comirnaty^® 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 30 mcg booster dose of Comirnaty^® Original & Omicron BA.4/BA.5 is considered favourable in individuals 12 years of age or older.

For further details about Comirnaty Original & Omicron BA.4/BA.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.