Regulatory Decision Summary for Pfizer-BioNTech COVID-19 Vaccine

The purpose of this submission was to expand the currently approved indication to children 12 to 15 years of age. The Phase 3 study C451001, that supported the original approval of the vaccine, was amended in October 2020 to include individuals 12 to 15 years of age. This submission provided an updated analysis of study C451001 that included data to support the safety and efficacy of the vaccine in individuals 12 to 15 years of age.

The study included 2260 adolescents 12 to15 years of age who were randomised equally to receive 2 doses of Pfizer-BioNTech COVID-19 Vaccine (n=1131) or placebo (n=1129). Young adults 16 to25 years of age served as a reference group for the immunogenicity and safety data of the 12 to15 years of age group.

Data was also provided as safety follow-up of the original approval in adults 16 to 55 years old; the data was collected up to six months after Dose 2.

Health Canada decision issued:

Pfizer-BioNTech COVID-19 Vaccine is now authorized for use under the Interim order respecting the importation, sale and advertising of drugs for use in relation to COVID-19, for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in adolescents 12 to15 years of age.

Date of decision:

2021-05-05

Indication (use):

Recommended Indication
Pfizer-BioNTech 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 12 years of age and older.

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

The efficacy, immunogenicity and safety of Pfizer-BioNTech COVID-19 vaccine were assessed in 2260 adolescents 12 to15 years of age (in the ongoing Study C4591001). In that study, participants were treated with two doses of the vaccine (n=1131) or placebo (n=1129), 21 days apart.

Based on cases reported from at least 7 days after Dose 2, it was demonstrated that in participants without evidence of prior infection with SARS-CoV-2, compared to placebo, efficacy of Pfizer-BioNTech COVID-19 vaccine was 100% (95% confidence interval of 75.3% to 100.0%). In participants with or without evidence of prior infection with SARS-CoV-2, compared to placebo, efficacy of Pfizer-BioNTech COVID-19 vaccine was also 100% (95% confidence interval of 78.1% to 100.0%). No severe COVID-19 cases were reported in the study.

The vaccine efficacy (VE) in adolescents 12 to15 years of age was therefore consistent with the VE previously demonstrated in the adult population.

A non-inferiority analysis of neutralizing titers/ antibodies was performed to compare levels between adolescents 12 to15 years of age and young adults 16 to25 years of age. After Dose 2, vaccination with the vaccine elicited SARS-CoV-2 neutralizing antibodies. The estimated ratio of antibody levels found in the 12 to 15 years of age group relative to the 16 to 25 years of age group was 1.76, with a 2-sided 95% CI of 1.47 to 2.10, meeting the 1.5-fold non-inferiority pre-established criterion.

With regard to the safety evaluation, 98.3% of the adolescents had at least 1 month of follow-up, and 57.9% of the adolescents (1308/2260) had at least 2 months of safety follow-up after Dose 2.

Overall, solicited adverse reactions (AR), reported within 7 days after any dose, included (frequency in %) 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%), and injection site redness (8.6%). Most of the adverse reactions were mild or moderate in severity. The severe solicited adverse reactions were reported in ≤1.5% for local ARs and in ≤3.5% for systemic ARs.

Unsolicited adverse events were reported by 6.4% of vaccine recipients and by 6.3% of placebo recipients. The serious unsolicited adverse events (SAEs) were reported by 0.4% of vaccine recipients and by 0.2% of placebo recipients. No mortality was reported in the clinical study. The observed AEs did not suggest any serious safety concerns for adolescents 12 to15 years of age.

For adverse events of special interest (AESI), lymphadenopathy was reported in 0.8% of participants of the vaccine group (9 cases) and in 0.2% in the placebo group (2 cases). No cases of Bells palsy, myocarditis, thrombocytopenia, or deep vein thrombosis were reported. No cases of anaphylaxis reactions to the vaccine were reported in the study.

Generally, reactogenicity profiles and unsolicited safety results in adolescents 12 to15 years of age were comparable to that in young adults 16 to25 years of age.

Follow-up on the safety of adult patients (16-55 years of age) was also provided. There were no new safety signals that were identified and thus the data continues to support the use of the vaccine in that age group.

The efficacy and immunogenicity of Pfizer-BioNTech COVID-19 vaccine has been demonstrated in individuals 12 to15 years of age. The efficacy in that age group is estimated to be 100% and is comparable to what is observed in adults. The safety data, with a follow-up time of up to two months after Dose 2, showed that the vaccine at the proposed dose of 0.3 ml is well-tolerated.

The Phase 3 study is ongoing and will continue to collect information on the long-term safety and efficacy of the vaccine. There are post-authorization commitments for monitoring the long-term safety and efficacy of Pfizer-BioNTech COVID-19 vaccine for immunization in adolescents 12 to15 years of age. Based on the totality of the information, the benefit-risk profile of Pfizer-BioNTech COVID-19 vaccine is considered favorable for active immunization in individuals 12 to15 years of age.

The Pfizer-BioNTech COVID-19 Vaccine is therefore recommended for authorization for use under the Interim order respecting the importation, sale and advertising of drugs for use in relation to COVID-19, for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in adolescents 12 to15 years of age.

Directions for use:

Pfizer-BioNTech COVID-19 Vaccine is administered intramuscularly after dilution as a series of two doses (0.3 mL each) 21 days apart.

Pfizer-BioNTech COVID-19 Vaccine is a suspension for intramuscular injection which must be diluted prior to administration.

For more information, refer to the Product Monograph for Pfizer-BioNTech 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.

Additional Terms and Conditions associated with the authorization for the indication to include use in individuals 12 to 15 years of age.

Clinical:

1. Provide safety data for all children 12 to15 years of age in study C4591001, 6-months after Dose 2, when the data become available.
2. Provide Study C4591001 report including safety, efficacy and immunogenicity data up to 2 years after Dose 2 in children 12 to15 years of age, when the data become available.

Risk Management Plan:

1. Provide the European Risk Management Plan with the Canadian Addendum adding information pertaining to the use in individuals 12 to 15 years of age to the safety specification, pharmacovigilance plan and risk minimization activities by May 25, 2021.
2. All post-market requirements including reporting of adverse reactions, monthly safety reports, patient information cards, signal assessment, etc. should continue to be submitted.