Regulatory Decision Summary for Spikevax

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):

Elasomeran

Therapeutic area:

Vaccines, for human use

Type of submission:

Supplement to a New Drug Submission (SNDS)

Control number:

263775
What was the purpose of this submission?

 

This submission intends to extend the indication of Spikevax to include active immunization to prevent coronavirus disease 2019 (COVID-19) in individuals 6 months to < 6 years of age administered as a primary series of 2 doses (25 mcg each) given 4 weeks apart.

Currently, Spikevax 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 6 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.

To support authorization of Spikevax in children aged 6 months to 5 years old, safety, immunogenicity, and efficacy data in the two age cohorts (2 years to 5 years and 6 months to < 2 years) from the ongoing study P204 were provided. In the 2 years to 5 years cohort, 4,038 participants received at least one dose of SPIKEVAX (n=3,031) or placebo (n=1,007), and 2,960 SPIKEVAX participants and 970 placebo participants received two doses; the median duration of follow-up was 103 days after dose 1, and 71 days after dose 2. In the 6 months to < 2 years cohort, 2,350 participants received at least one dose of SPIKEVAX (n=1760) or placebo (n=590), and 1,574 Spikevax participants and 530 placebo participants received two doses; the median duration of follow-up was 98.0 days after dose 1, and 68.0 days after dose 2.

Available data support the efficacy of Spikevax in preventing COVID-19 in children 6 months to 5 years of age. For each of the two age cohorts, vaccine efficacy (VE) was inferred by immunobridging, based on a comparison of neutralizing antibody responses with formal hypothesis testing, to a young adult age group (18 to 25 years) for whom VE had been demonstrated in a Phase 3 efficacy trial. The results showed that the immune response to Spikevax in children 2 years to 5 years of age and 6 months to < 2 years of age (2 doses; 25 mcg each dose) was comparable to that seen in subjects 18 to 25 years of age (2 doses; 100 mcg each dose).

In addition, descriptive efficacy analyses for each of the two age cohorts provided VE estimates that were consistent with VE estimates observed in adults during the period when the B.1.1.529 (Omicron) variant was the predominant variant in circulation, based on observational studies. VE for preventing COVID-19 14 days or more after dose 2 using the “CDC case definition” was 36.8% for children 2 years to 5 years of age and 50.6% for children 6 months to <2 years of age.

No emergent safety concerns were identified in the study. In the infant and young toddler study group (6 months to < 2 years of age), the most frequently reported adverse reactions following administration of Spikevax were irritability or crying (64.3%), pain at the injection site (46.2%), sleepiness (35.1%), and loss of appetite (32.1%). In the older age group (2 years to 5 years of age), pain at the injection site (71.4%) was the most common adverse reaction. In the older toddler subgroup (2 years to 36 months of age), other frequently reported adverse reactions were pain irritability or crying (54.3%), sleepiness (36.0%) and loss of appetite (30.5%). In the preschooler subgroup (37 months to 5 years of age), another frequently reported adverse reactions was fatigue (48.4%).

Other less common reactions among the entire study group (6 months to 5 years) included fever, redness and swelling at the injection site, nausea or vomiting, swollen or tender lymph nodes under the arm, headaches (in older children) and muscle and/or joint aches. The adverse reactions were usually mild or moderate resolving within a few days of vaccination. There were no deaths, and no cases of myocarditis or pericarditis reported during the study period. Three cases of anaphylaxis were documented across the entire study group (6 months to 5 years), all occurring > 14 days after vaccination, and attributed to other causes such as food or drug allergies.

The evidence indicates that the immunogenicity/efficacy and safety of Spikevax in children 6 months to 5 years of age are consistent to those in young adults (18 to 25 years of age). Therefore, the benefit-risk profile of Spikevax is considered favourable for use as a 2-dose series (25 mcg each dose, 4 weeks apart) in children 6 months to 5 years of age, especially in children at higher risk of severe COVID-19.

There are some uncertainties or limitations at the current time, including unavailable 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 5 years of age; the safety and efficacy in subjects with severe comorbidities or who are immunocompromised. The limitations are mitigated by Terms and Conditions, and by 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.

Spikevax 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.

 

Decision issued

Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.