Regulatory Decision Summary for Covifenz
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.
Type of submission:
What was the purpose of this submission?
The purpose of this submission is to request expansion of the current approved age indication to include use in the elderly ≥65 years of age.
After evaluation of the submitted data package, Health Canada authorized COVIFENZ for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 in individuals 18 years of age and older.
Why was the decision issued?
Data from study CP-PRO-CoVLP-021 were provided to support the request for the expansion of the current approved indication to include use in the elderly ≥65 years of age. Original vaccine efficacy against symptomatic infection was previously shown in adults 18-64 years of age and estimated to be 71.0 % (95% CI: 58.7, 80.0). Data in the form of an immunobridging analysis was provided to support the extension of the indication for COVIFENZ from active immunization to prevent COVID-19 in individuals 18 years to 64 years of age to include those 18 years of age and older, based on data obtained in the Phase 2/3 Study CP-PROCoVLP-021.
The phase 2 of Study 021 was a randomized, observer-blind, multi-centre, placebo-controlled study to evaluate the safety and immunogenicity of Covifenz, compared to placebo. The study was conducted in Canada and the United States. The subjects included healthy adults 18-64 years of age (population 1), healthy elderlies 65 years of age and older (population 2) and adults with significant comorbidities, 18 years of age and older (population 3).
Phase 3 of Study 021 evaluated the safety, efficacy and immunogenicity of Covifenz, two doses administered with a 21-day interval, compared to placebo, in subjects 18 years of age and older in North America, South America and the United Kingdom.
The immune response in elderly subjects ≥65 years of age 21 days following the second dose (Day 42) of Covifenz was compared to healthy adults 18 to 64 years of age 21 days following the second dose (Day 42) in which vaccine efficacy was previously shown. This comparison was assessed in subjects who had no evidence of past SARS-CoV-2 infection at baseline. Overall, the antibody levels were 1.23-fold higher in the elderly population relative to the healthy adult.
In the elderly ≥65 years of age populations, participants had been followed for safety for 9.4 months in the Covifenz group and 5.9 months in the placebo group. Solicited local and systemic adverse reactions (ARs) were reported more frequently among subjects in the COVIFENZ group than in the placebo group. Pain at the injection site was the most frequently reported local reaction within 7 days after each dose, with muscle aches and fatigue reported frequently. Incidences of local reactions in the ≥65 years of age bracket were generally similar to incidences reported in the 18 to 64 years of age bracket. The ARs after vaccination were usually of mild or moderate intensity and resolved within a few days. The incidence of Grade 3 (severe) solicited local events (local) was higher after the second vaccination (6.5 %) than first vaccination (0.5 %) of the Covifenz group. There were no Grade 4 (potentially life-threatening) ARs reported in either Covifenz group or placebo group. No deaths or serious events related to Covifenz were reported. The safety profile of Covifenz in the elderly ≥65 years of age was similar to that observed in the 18 to 64 years of age bracket and no new safety signals were identified.
There were no notable patterns or numerical imbalances between treatment groups for specific categories of serious adverse events that would suggest a causal relationship to the vaccine. No cases of facial palsy (Bell’s palsy), anaphylactic shock/shock, narcolepsy, myocarditis, pericarditis, or thrombosis with thrombocytopenia syndrome were reported in the ≥65 years of age bracket. The study is ongoing and the safety data continues to be collected.
An important limitation to the data is that circulating SARS-CoV-2 viral variants may be associated with breakthrough infections in individuals that have received a primary vaccination series of COVIFENZ. However, clinically, it is expected that ancillary immune mechanisms make a significant impact to the robustness and durability of the overall vaccine induced immune response to SARS-CoV-2. This risk is mitigated through accurate and transparent labelling in the product monograph. Additionally, the currently imposed outstanding Terms and Conditions on the drug product related to Clinical data are considered adequate to mitigate the risk associated with the limitations identified in review of the submission.
Risk Management Plan (RMP).
An updated Canadian Risk Management Plan (RMP) Addendum was included in the submission to expand the currently approved indication to individuals ≥65 years of age. 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 to be acceptable with follow-up and identified appropriate monitoring (pharmacovigilance) activities and risk minimization measures based on the safety profile of this vaccine. This included providing information in the product monograph and identifying populations where more data is needed. In addition to regulatory requirements for post-market monitoring and prioritized reporting of adverse events following immunization, safety reports on the vaccine will be provided to Health Canada. Results related to safety and effectiveness from ongoing and planned studies will be submitted as they become available.
Based on the totality of the information, the benefit-risk profile for Covifenz is considered favourable for active immunization to prevent COVID 19 in individuals 65 years of age and older.
For further details about Covifenz, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.
Authorized; issued a Notice of Compliance in accordance with the Food and Drug Regulations