Regulatory Decision Summary for Janssen COVID-19 Vaccine

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):

AD26.COV2.S (recombinant)

Therapeutic area:

Vaccines, for human use

Type of submission:

Supplement to a New Drug Submission

Control number:

259715
What was the purpose of this submission?

 

The purpose of this submission is to seek authorization for a booster dose of Janssen COVID-19 Vaccine for active immunization for the prevention of COVID-19 caused by SARS-CoV-2 in individuals 18 years of age or older.

 

Why was the decision issued?

 

COVID-19 is the infectious disease caused by the coronavirus, SARS-CoV-2, that was discovered in late' 2019. In Canada, there have been 3,484,560 confirmed cases of COVID-19 and approximately 37,626 deaths as of April 1, 2022, and these numbers are still increasing. It is predominantly a respiratory illness that can affect other organs. People with COVID-19 have reported a wide range of symptoms from no to mild symptoms to severe illness to death.

Based on a favourable benefit-risk profile established from the efficacy, immunogenicity, and safety data' provided from clinical trials, Janssen COVID-19 Vaccine is authorized in Canada for active immunization' for prevention of COVID-19 caused by SARS- CoV-2 in individuals 18 years of age and older. The current vaccination schedule for the vaccine consists of a single-dose (0.5 mL; 5×1010 vp) primary vaccination administered intramuscularly.

With the emergence of highly transmissible variants (e.g. Delta, Omicron, etc.) of SARS-CoV-2, declining neutralizing antibody titers, and the suggestion that effectiveness of the primary vaccination may be waning with a lengthened period of time since completion of the single-dose, the need for booster doses in fully vaccinated individuals has been raised.

The pivotal data supporting authorization of the Janssen COVID-19 Vaccine booster dose comes from' ENSEMBLE 2. ENSEMBLE 2 is an ongoing, randomized, double-blind, placebo-controlled Phase 3 study conducted in Europe, South Africa, North America, South America, and Asia. Randomization was stratified by age (18-59 years, 60 years and older) and presence or absence of comorbidities associated with an increased risk of progression to severe COVID-19. The efficacy and safety of a booster dose of the vaccine (5×1010 vp) was evaluated in participants, living in, or going to locations with high risk for acquisition of SARS-CoV-2 infection. The primary objective was to demonstrate the efficacy of the vaccine (2-dose regimen with a 56-day interval) in the prevention of molecularly confirmed, moderate to severe/critical COVID-19 (with onset at least 14 days after the second vaccination), as compared to placebo, in SARS-CoV-2 seronegative adults.

A total of 31,300 individuals were randomized in the double-blind phase of the study (15,708 received the' vaccine and 15,592 received placebo) and a total of 16,751 individuals received two doses (8,655 received the vaccine and 8,096 received placebo). In total, 14,492 individuals were included in the per-protocol efficacy population (7,484 received the vaccine and 7,008 received placebo). Vaccine Efficacy (VE) estimates against moderate to severe/critical COVID-19 and against severe/critical COVID-19 at least 14 days post-booster dose were 75.2% (95% CI: 54.6; 87.3) and 100% (95%CI: 32.6; 100.0), respectively.

The efficacy data were collected when the Alpha variant was the primary strain of the virus circulating and prior to the emergence of the Omicron variant. As an existing term and condition associated with' authorization, Janssen Inc. is required to provide data regarding protection against current and emerging' variants of concern, when available.

In the full analysis set, a total of 8,646 individuals received a second dose during the double-blind phase. In the reactogenicity subset, from the 3,016 individuals who received 1 dose of the vaccine, 1,559 individuals received a second dose during the double-blind phase. The median age of individuals was 53 years (range: 18-99 years). At the data-cut off date of June 25, 2021, the median follow-up duration after the booster dose with the vaccine was 38 days. The solicited adverse reaction profile for the booster dose was similar to that after the first dose. There were no new safety signals identified.

As ENSEMBLE 2 is ongoing and will continue to collect data on the long-term efficacy and safety of the' booster, Health Canada will review these data as they become available and the submission of the longer' term data is an existing term and condition for the vaccine.

The Risk Management Plan (RMP) was reviewed and considered acceptable. The RMP identified' appropriate monitoring (pharmacovigilance) activities and risk minimization measures based on the safety' profile of this vaccine. Overall, the list of safety concerns and the corresponding pharmacovigilance and risk minimization activities of Janssen COVID-19 Vaccine given as a booster dose are considered sufficient and adequately reflected in the Canadian Addendum RMP as well as in the Canadian Product Monograph.

In addition to regulatory requirements for post-market monitoring and prioritized reporting of adverse events following immunization, safety summary reports on the vaccine 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 booster dose, will be submitted as they become available.

Based on the totality of the information, the benefit-risk profile for a 0.5 mL (5×1010 vp) homologous booster dose of the Janssen COVID-19 Vaccine at least 2 months after the primary vaccination is considered favourable in individuals 18 years of age and older. With the data currently available to Health Canada, there are insufficient data to support a heterologous booster dose for the vaccine. Moreover, the exact timing of the homologous booster dose and appropriate populations to administer booster doses will depend on a variety of factors including the local epidemiological contexts which are continually evolving and may vary between provinces and territories. As such, standardized timing is not currently recommended and the decision for when and for whom to implement a booster dose should be made considering relevant vaccine effectiveness (e.g. evidence of waning effectiveness), safety and immunogenicity data.

 

Decision issued

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