Regulatory Decision Summary for Covifenz

To support authorization of Covifenz (or CoVLP), a Phase 1 (Study 019) and a Phase 2/3 Study (Study 021) with Covifenz were included in the submission. Covifenz contains antigens derived from the original strain of SARS-CoV-2. The two studies are still ongoing.

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). Geometric mean titers (GMTs) for neutralizing antibody (Nab) in populations 1, 2 and 3 of the vaccine group were 5.3, 5,2 and 8.9, respectively at the baseline, 44.3, 29.7 and 49.1, respectively, 3 weeks after the first dose, and then further increased to 2033.6, 1917.7 and 1962.0, respectively, 3 weeks after the second dose. The seroconversion rate in populations 1, 2 and 3 of the vaccine group was 99.2%, 97.7% and 95.8%, respectively, 3 weeks after the administration of the second dose. Covifenz also induced a balanced cell-mediated immune response.

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 study was initiated on 15 March 2021, and 24,076 subjects (99.7 %) received at least one dose of Covifenz or placebo.

At the cut-off date to evaluate efficacy (20 August 2021), 157 participants had RT-PCR confirmed COVID-19 occurring ≥ 7 days post dose 2 in the per-protocol (PP) analysis set. There were 39 cases in the vaccine group and 118 cases in the placebo group. The vaccine efficacy (VE) was estimated to be 71.0 % (95% CI: 58.7, 80.0). There were two cases with severe COVID-19 which occurred ≥ 7 days following the second dose. These cases were in the placebo group.

As of 3 December 2021, 114 of the 157 cases (72.6 %) had been sequenced. The cases in the vaccine group were caused by the Delta (n=11) and Gamma (n=6) strains. The cases in the placebo group were caused by the Alpha (n=5), Delta (n=39), Gamma (n=46), Lambda (n=3), and Mu (n=4) strains. None of the cases was caused by the original strain. The two severe COVID-19 cases observed in the placebo group were caused by the Gamma or Mu strain.

At the cut-off date of 25 October 2021 for the safety data, 16,562 (68.8%) subjects (9,599 and 6,963 in the vaccine and placebo group, respectively) had at least two-month safety follow-up after the second dose. The median follow-up after the second dose was 3.1 months in the vaccine group and 2.5 months in the placebo group.

Solicited local and systemic adverse events (AEs) reported within 7 days after each dose, were more frequent among subjects in the Covifenz group than in the placebo group. The most reported solicited local and systemic AEs in adults 18 to 64 years old, after receiving the first and/or second dose were pain at injection site (92.5 %), headache (68.5 %), muscle aches (67.8 %), fatigue (64.7 %), feeling of general discomfort (63.8 %), chills (46.7 %), joint aches (40.0 %), swelling at injection site (38.0 %), swelling in the neck (22.2 %), erythema at injection site (20.1 %), swelling in the axilla (15.1 %) and fever (9.7 %). The AEs after vaccination were usually of mild or moderate intensity and resolved within a few days (1 to 3 days). Grade 3 and higher solicited AEs were <1.6%.

A total of 26.3 % of the participants in the Covifenz group and 23.1 % of the participants in the placebo group experienced an unsolicited AE (includes both non-serious and serious unsolicited AEs).

The most reported non-serious unsolicited adverse events in adults 18 to 64 years old after receiving the first and/or second vaccination in Covifenz or placebo group occurring in ≥ 1.0 % of the participants were: headache (4.2 % and 3.8 %, respectively), nasal congestion (2.5 % and 2.3 %, respectively), influenza (2.1 % and 1.9 %, respectively), oropharyngeal pain (1.6 % and 1.7 %, respectively), cough (1.4 % and 1.3 %, respectively), catarrh (1.1 % and 0.9 %, respectively), diarrhea (1.4 % and 1.1 %, respectively), nausea (1.3 % and 0.8 %, respectively), myalgia (1.4 % and 1.0 %, respectively) and influenza-like illness (1.4 % and 1.3 %, respectively). In addition, lymphadenopathy was reported at 0.4 % in the Covifenz group and 0.2 % in the placebo group. No deaths reported were related to Covifenz.

A Core Risk Management Plan (RMP) and a Canadian RMP Addendum were included in the submission for Covifenz. 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 and identified appropriate monitoring (pharmacovigilance) activities and risk minimization measures based on the known safety profile of Covifenz. This included providing information in the product monograph and identifying populations where more data are needed. 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 on the vaccine are required to be submitted to Health Canada. Results from ongoing and planned studies related to safety and effectiveness of the vaccine will be submitted as they become available.

An important limitation of the data is the lack of information on the long-term safety and efficacy of the vaccine. The safety and efficacy has not been established in elderly, children and pregnant woman. The identified limitations are managed through labelling and the Risk Management Plan. The Phase 3 Study is ongoing and will continue to collect information on the long-term safety and efficacy of the vaccine. There are post-authorization commitments for monitoring the long-term safety and efficacy of Covifenz.

Manufacture of Covifenz consists of production of the recombinant coronavirus-like particle SARS-CoV-2 spike protein from the original strain, using a plant-based system. This protein is then mixed with the AS03 adjuvant prior to administration. Evidence was provided to demonstrate that the vaccine is manufactured under Good Manufacturing Practices (GMP) at all manufacturing sites providing supply to Canada, and that in-process controls, process parameters, and quality control release tests have been established to monitor product quality throughout the process. The specifications used to evaluate key quality attributes and consistency of production were found acceptable. This information, together with the terms and conditions imposed on the authorization, support authorization.

Based on the totality of the information, the benefit-risk profile for Covifenz for the active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 18 to 64 years of age is considered favourable. The efficacy of the vaccine was established and the vaccine was well tolerated by participants. Covifenz is therefore recommended for authorization under Division 8 of the Food and Drug Regulations.