Regulatory Decision Summary for Janssen COVID-19 Vaccine

 

The purpose of this submission was to seek market authorization, via the Interim Order Respecting the Importation, Sale and Advertising of Drugs for Use in Relation to COVID-19, for the Janssen COVID-19 Vaccine (Ad26.COV2.S, recombinant) which was developed for active immunization to prevent COVID-19.

Health Canada decision issued:

Janssen COVID-19 Vaccine was authorized for use in relation to the COVID-19 pandemic, in accordance with section 5 of the Interim Order Respecting the Importation, Sale and Advertising of Drugs for Use in Relation to COVID-19.

Date of decision:

2021-03-05

Indication (use):

Janssen COVID-19 Vaccine (Ad26.COV2.S, recombinant) is indicated for active immunization against coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) in persons 18 years of age and older.

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

The ongoing COVID-19 pandemic has a significant impact on public health. The availability of safe and effective vaccines will reduce the spread and severity of COVID-19 disease and reduce its social and economic consequences.

Known and potential benefits:
The primary efficacy analysis are based on an interim analysis (January 22, 2021) of the data from Study COV3001. At the time of analysis, half of study participants were followed-up for at least two months following vaccination. The study was conducted in North America, Latin America and South Africa.

In Study COV3001, 44,325 participants were randomized, 21,895 in the vaccine group and 21,888 in the placebo group.

For the co-primary endpoint, with onset at least 14 days after vaccination, there were 116 cases of moderate to severe/critical COVID-19 in the vaccine and 348 in the placebo groups, respectively. Vaccine efficacy (VE) was therefore evaluated to be 66.9% (95% confidence interval (CI): 59.0; 73.4).

For the co-primary endpoint with onset at least 28 days after vaccination, there were 66 cases of moderate to severe/critical COVID-19 in the vaccine and 193 in the placebo groups, respectively. Vaccine efficacy was therefore evaluated to be 66.1% (95% CI: 55.0; 74.8).

Higher VE was observed against severe/critical COVID-19. The VE was 76.7% (95% CI: 54.56; 89.09) as of 14 days and 85.4% (95% CI: 54.15; 96.90) as of 28 days after vaccination.

In Study COV3001, 34.6% of participants were ≥60 years of age. The vaccine showed consistent efficacy across age groups against moderate to severe/critical COVID-19, and also when looking at severe/critical COVID-19 only. VE was also consistent between genders, between Hispanics and non-Hispanics, and between Black/African Americans and Caucasians. Across geographical regions, VE ranged from 52.0% (South Africa) to 74.4% (US). Differences in regional viral strains may explain some of these differences in the vaccine efficacy. However, the vaccine seems to have maintained its efficacy against severe and critical COVID-19, even in the presence of viral variants.

Known and potential risks:
The Janssen COVID-19 Vaccine exhibits moderate reactogenicity. The most frequently-reported adverse reactions (ARs) after the single dose were pain at the injection site (48.7%), headache (39.0%), fatigue (38.3%), and myalgia (33.2%). The majority of these ARs were mild to moderate in severity and resolved within 1 to 3 days. Both local and systemic ARs were less common in participants ≥60 years of age. Serious adverse events, unrelated to COVID-19, occurred in 0.4% of participants in both the vaccine and placebo groups. Hypersensitivity adverse events were more common in the vaccine group (0.4%) than in the placebo group (0.3%). One case of anaphylaxis has been reported in an ongoing open-label trial (COV3012). Small imbalances in thromboembolic events (15 vs. 10), tinnitus (6 vs. 0) and seizures (4 vs. 1) were noted. As a contributory effect of the vaccine could not be excluded for a minority of these events, they will be followed post-market.

A Risk Management Plan (RMP) was established for Janssen COVID-19 Vaccine. The RMP is designed to describe known and potential safety issues, to present the monitoring plan and, when needed, to describe measures that will be put in place to minimize risks associated with the product. Upon review, the RMP was considered acceptable and identified appropriate monitoring (pharmacovigilance) activities and risk minimization measures based on the safety profile of the product. Important limitations of the data at this time include the lack of information on the long-term safety and effectiveness of the vaccine, interactions with other vaccines, and the lack of data in sub-populations (e.g. pregnant/breastfeeding women, pediatric population <18 years of age, patients with autoimmune or inflammatory disorders, immunocompromised patients and frail patients with comorbidities). The identified limitations are managed through labelling and the RMP. The RMP will be updated to reflect additional safety information as it is collected. In addition to regulatory requirements for post-market monitoring and prioritized reporting of adverse events following immunization, monthly safety summary reports will be provided to Health Canada.

Manufacturing of the Janssen COVID-19 Vaccine consists of the production of an Adenovirus Serotype 26 (Ad26) that cannot replicate and encodes a stabilized spike protein of the SARS-CoV-2 virus. Evidence was provided to demonstrate that the vaccine is manufactured using Good Manufacturing Practices (GMP) at manufacturing sites; process parameters and quality control release tests have been established to monitor product quality throughout the manufacturing process. The specifications used to evaluate key quality attributes and consistency of production were found acceptable.

Based on the totality of the information, the benefit-risk profile of Janssen COVID-19 Vaccine is positive for the proposed indication in adults 18 years and over.

In conclusion, the Janssen COVID-19 Vaccine is 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 against coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 18 years old and over. The efficacy of the vaccine was estimated to be 66.9%. Overall, there are no important safety concerns and the vaccine was well tolerated by participants.

For more information on Health Canadas decision, please view the Summary Basis of Decision.

Directions for use:

Janssen COVID-19 Vaccine is a colorless to slightly yellow, clear to very opalescent suspension. The vaccine should be inspected visually for particulate matter and discoloration prior to administration. The vial should be inspected visually for cracks or any abnormalities, such as evidence of tampering prior to administration. If any of these should exist, do not administer the vaccine.

Each vaccine dose of 0.5 mL is withdrawn into a syringe for injection to be administered intramuscularly, preferably in the deltoid muscle. Use a separate

sterile needle and syringe for each individual. It is normal for liquid to remain in the vial after withdrawing the final dose.

The vaccine does not contain any preservative. After first puncture, use the vial/filled syringe within:

• 3 hours when stored at room temperature (up to 25 °C), or
• 6 hours when stored in a refrigerator (2 to 8°C).

Janssen COVID-19 Vaccine is stable for a total of 12 hours at 9°C to 25°C in an unpunctured vial. It is not a recommended storage or shipping condition but may guide decisions for use in case of temporary temperature excursions.

For more information, refer to the Product Monograph for the Janssen 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.

For more information, refer to the Authorization Terms and Conditions for Janssen COVID-19 Vaccine.