Regulatory Decision Summary for Comirnaty

Review decision

The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.


Product type:

Drug

Medicinal ingredient(s):

Tozinameran

Therapeutic area:

Vaccines, for human use

Type of submission:

Supplement to a New Drug Submission

Control number:

265483
What was the purpose of this submission?

 

This submission intends to extend the indication of Comirnaty to include active immunization to prevent coronavirus disease 2019 (COVID-19) in individuals 6 months to 4 years of age administered as a primary series of 3 doses (3 mcg each) with the initial two doses given 3 weeks apart followed by a third dose given at least 8 weeks after the second dose.

Currently, Comirnaty is indicated for active immunization against coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in individuals 5 years of age and older.

 

Why was the decision issued?

 

COVID-19 is a serious and potentially life-threatening disease in children. Vaccination is one of the most effective ways to protect children against the disease.

The authorization was supported by safety and immunogenicity data generated in pediatric participants aged 6 months to 4 years old as part of an ongoing Phase 2/3 randomized, observer-blind and placebo-controlled study in the United States, Finland, Poland, Brazil and Spain. A total of 4,526 participants 6 months through 4 years of age were randomized 2:1 to receive two doses of 3 mcg Comirnaty or placebo 3 weeks apart (3,013 in the vaccine group and 1,513 in the placebo group). A third dose of 3 mcg was added at least 8 weeks after Dose 2 as part of the primary series to obtain the desired immune response; a total of 1,456 participants received a third dose (992 in the vaccine group and 464 in the saline placebo group), representing 32.2% of randomized participants.

Vaccine effectiveness was inferred by immunobridging, based on a comparison of immune responses of each age group (6 months to 2 years; and 2 years to 4 years of age) to a young adult age group (16 to 25 years) for whom the vaccine efficacy had been demonstrated in an efficacy trial. Immunobridging success criteria were met in each age group after Dose 3. The results showed that the immune responses to COMIRNATY in children 6 months to 4 years of age (3 doses; 3 mcg each dose) was comparable to that seen in young adults 16 to 25 years of age (2 doses; 30 mcg each dose), suggesting a similar vaccine effectiveness against COVID-19. Additional descriptive immunogenicity data showed that three doses of the vaccine 3-mcg in children 6 months through 4 years of age induced higher neutralizing titers against the Omicron (BA.1) variant compared to after two doses.

Descriptive analyses provided Vaccine Efficacy (VE) estimates in children 6 months to 4 years of age were consistent with the VE demonstrated in the adult efficacy trial. The number of subjects included in the analysis of post dose 3 vaccine efficacy and the duration of follow-up post dose 3 are limited at the cut-off date of 29 April 2022. Terms and Conditions requires that Pfizer BioNTech provide the vaccine efficacy final analysis when the protocol specified number of at least 21 cases for VE analysis post-Dose 3 was reached.

Severe COVID-19-related outcomes after Dose 3 did not occur. 

For the safety analysis, the study randomly enrolled 1,776 children 6 months to 2 years (1,178 in the vaccine group and 598 in the placebo group). Of these, the median follow-up duration was 6 months after the second dose. In the 2 to 4 years cohort, the study enrolled 2,750 participants (1,835 in the vaccine group and 915 in the placebo group). Of these, the median follow-up duration was 4 month after the second dose. A total of 1,456 children 6 months to 4 years of age received a third dose (992 in the vaccine group and 464 in the placebo group) and have been followed for a median of 1.3 and 1.4 months after the third dose in children 6 months to 2 years and 2 years to 4 years of age cohorts respectively, during the blinded and placebo controlled follow up period.

The safety profile in children 6 months to 4 years of age was comparable to that observed in children 5 to 12 years old. In children 6 months to 2 years of age group, the most  frequently reported adverse reactions following administration of Comirnaty were irritability (68.4%), decreased appetite (38.6%) and tenderness at the injection site (26.4%). In children 2 to 4 years of age group the most frequently reported adverse reactions were pain at the injection site (47.0%) and fatigue (44.8%). Other less common reactions among
the entire study group (6 months to 4 years) included redness and swelling at the injection site, nausea or vomiting, headaches (in older children) and fever (up to 14.4%). The adverse reactions were usually mild or moderate resolving within a few days of vaccination. There were three cases of swollen or tender lymph nodes under the arm reported in the vaccine group (two in 6 months to 2 years cohort and one in 2 to 4 years cohort) resolving within a few days and 0 case in the placebo group.

There were no cases of myocarditis/pericarditis, Bell’s palsy (or facial paralysis/paresis), vaccine related anaphylaxis, or deaths reported as of the data cut-off date (29 April 2022). No serious adverse events were reported that were considered related to vaccination. The adverse events observed showed that the vaccine was safe and well-tolerated in children within demographic subgroups based on age, sex, race/ethnicity, country and baseline SARSCoV-2 status (positive). No emergent safety concerns were identified in the study.

Limitations at the current time include the lack of longer term safety, immunogenicity and efficacy data; the uncertainty around the risk of very rare events such as myocarditis and pericarditis post-vaccination in children 6 months to 4 years of age; the safety and efficacy in subjects with severe comorbidities or who are immunocompromised. The limitations are mitigated by Terms/Conditions, labelling and the Risk Management Plan (RMP).

The RMP was reviewed and considered acceptable. The RMP identified appropriate monitoring (pharmacovigilance) activities and risk minimization measures based on safety profile of this vaccine. This included providing information in the product monograph and identifying special populations where more data is needed. In addition to regulatory requirements for post-market monitoring and prioritized reporting of adverse events following immunization, safety summary reports will be provided on a regular basis to Health Canada for review. Results related to safety and effectiveness from ongoing and planned studies, including the pediatric population, will be submitted as they become available.

Available data support the immunogenicity/effectiveness and safety of the vaccine in preventing COVID-19 in the age group of 6 months through 4 years. The benefit-risk profile of Comirnaty is considered favourable in children 6 months to 4 years of age for use as a 3-dose primary series (3 mcg each dose) with two doses given 3 weeks apart followed by a third dose given at least 8 weeks after the second dose.

Comirnaty is therefore recommended for authorization under Food and Drug Regulations for drugs for use in relation to COVID-19, for active immunization against coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in individuals 6 months of age and older.

For further details about Comirnaty, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database."

 

Decision issued

Authorized; issued a Notice of Compliance (NOC) in accordance with the Food and Drug Regulations.