Regulatory Decision Summary for Nuvaxovid

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):

COVID-19 Vaccine (recombinant protein, adjuvanted)

Therapeutic area:

Vaccine for human use

Type of submission:

Supplement to a New Drug Submission

Control number:

265342
What was the purpose of this submission?

 

The purpose of this SNDS application is to seek authorization for Nuvaxovid for active immunization to prevent COVID-19 caused by the SARS-CoV-2 in adolescents 12 to 17 years of age to expand the indication currently approved for 18 years of age and older.

Nuvaxovid (COVID-19 Vaccine [Recombinant protein, Adjuvanted]) is a suspension of the severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2) recombinant spike protein (original Wuhan strain), with a Matrix-M adjuvant containing saponins.

 

Why was the decision issued?

 

Coronavirus disease 2019 (COVID-19) is the infectious diseases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first discovered as a human pathogen in late 2019 that led to the world’s worse pandemic in a century.

Due to low concern regarding COVID-19 complications, adolescents and children are more likely to remain unvaccinated compared to older adults in Canada Since 2021, two monovalent mRNA COVID-19 vaccines have been approved for use in adolescents as a primary series. By later 2022, two bivalent mRNA vaccines (i.e., containing the original Wuhan strain and a variant of concern Omicron (e.g., BA.1, BA.4 and BA.5 lineages)) were subsequently approved for use in Canada. Nuvaxovid would become the first vaccine product not using mRNA as the vaccine platform to be approved for use in Canadian adolescents.

Benefit of Nuvaxovid was established showing non-inferiority in neutralizing antibodies (NA) against SARS-CoV-2 wild type virus 14 days after a completed Nuvaxovid two dose series comparing a subset of COVID-19 naïve adolescents (12 to 17 years of age) with a similar subset of young adults (18 to 25 years of age) from the original phase of Study 301.

This vaccine benefit was also supported by descriptive efficacy analysis evaluating PCR-confirmed symptomatic mild, moderate or severe COVID-19 cases with 20 cases with 6 infections in the vaccinated group and 14 cases in the placebo group observed resulting in a point estimate of vaccine efficacy of 79.5%. During the course of the adolescent sub-study, there were 0 cases of moderate or severe COVID-19 reported in. At the time of this analysis, the Delta (B.1.617.2 and AY lineages) Variant of Concern (VOC) was the predominant variant circulating.

Demographic and baseline characteristics were balanced amongst participants who received Nuvaxovid and those who received placebo reflecting the diversity in the North American population. Safety was assessed in all adolescents who received at least one of the trial vaccines (Nuvaxovid or placebo) with the median age of recipients being 14-years-old, but with more younger adolescents (12 to 14 years old) who represented 67% of all participants.

Risk of the vaccine was determined by assessing the data from all participants with one dose of trial vaccine (Nuvaxovid or placebo). This included assessing local injection-site as well as systemic reactions within 7 days following the first and second dose, which were comparable to adult recipients in the earlier phase of the same study. The frequency of local and systemic reactions was higher with Nuvaxovid compared with placebo following the first dose (65.9% of recipients in total versus 29.8%, respectively) as well as with the second dose for Nuvaxovid (76.0%) compared with first dose whereas there was no increase with placebo (20.8%). The most common local reaction was injection-site tenderness followed by pain, erythema and swelling expected from a vaccine with a robust immune response. Headaches were the most common postvaccine systemic reaction by fatigue, muscle pain and malaise. The median duration of local and systemic reactions was about 1-2 days and self-limited.

Additionally, unsolicited Adverse Event (AEs) assessed from the day after receiving the first dose to the end of the study period (more than 2 months long) were similar in frequency for the Nuvaxovid group (16.3%) and placebo group (15.8%) with few serious adverse events, and no deaths or anaphylaxis during the adolescent sub-study. No one stopped the trial because of post-vaccine adverse events. There were no new safety signals of interest such as myocarditis or pericarditis as cases were all accounted for in the original adult study assessment.

As with all vaccines, rare cases of severe allergic reactions may occur within 30 minutes following vaccination. Inflammation of the heart such as myocarditis or pericarditis may also occur in at risk individuals such as young men age 12 to 30 years old. Should such rare post-vaccination reactions occur, the individual requires standard medical attention to appropriately manage.

The Risk Management Plan (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.

Overall, the benefit of using Nuvaxovid is considered favorable compared with generally mild and self-limiting vaccine-related risks, with risk mitigation measures described in the proposed Product Monograph (PM). Novavax has committed to updating the Product Monograph (PM) for Nuvaxovid with safety and vaccine efficacy or effectiveness data on an ongoing basis.

For further details about Nuvaxovid (COVID-19 Vaccine [Recombinant protein, Adjuvanted]), 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.