Regulatory Decision Summary for COVID-19 Vaccine Moderna

The purpose of this submission was to expand the currently authorized indication for the Moderna COVID-19 Vaccine to individuals 12 to 17 years of age, under the Interim Order respecting the importation, sale and advertising of drugs for use in relation to COVID-19. To support the authorization of the Moderna COVID-19 Vaccine in this population, the vaccine safety, efficacy and immunogenicity in participants 12 to 17 years of age was evaluated in Study P203, an ongoing Phase 2/3, randomized, observer-blind, placebo-controlled clinical trial.

Health Canada decision issued:

COVID-19 Vaccine Moderna was authorized for use in individuals 12 years of age and older 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:

2021-08-27

Indication (use):

The following is the indication for COVID-19 Vaccine Moderna for use in relation to COVID-19:

COVID-19 Vaccine Moderna (mRNA-1273 SARS-CoV-2 vaccine) is indicated for active immunization against coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in individuals 12 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 helps reduce the spread and severity of COVID-19 disease and reduce its social and economic consequences.

The vaccine safety, efficacy and immunogenicity in adolescents 12 to 17 years of age was evaluated in the ongoing Phase 2/3, randomized, observer-blind, placebo-controlled clinical study P203 (data cut-off date of May 8th, 2021). A total of 3,732 adolescents 12 to 17 years of age were enrolled in the study and randomised 2:1 to receive 2 doses of the vaccine or placebo 28 days apart. Participants with known history of SARS-CoV-2 infection were excluded from the study. All participants will be followed for the assessment of safety, efficacy and immunogenicity for up to 1 year after Dose 2 of the vaccination.

Compared to placebo, the vaccine efficacy (VE) in participants with first COVID-19 occurrence from 14 days after Dose 2 was 100% (two-sided 95% confidence interval [CI] of 28.9% to 100%); there were 0 confirmed COVID-19 cases identified in the vaccine group (N=2,162) and 4 in the placebo group (N=1,073). The vaccine efficacy demonstrated in adolescents 12 to 17 years of age is consistent with the VE previously demonstrated in the adult population.

Measurements of neutralizing antibody titers were performed to support efficacy in adolescents. Differences between neutralizing antibody levels in adolescents 12 to 17 years of age and young adults 18 to 25 years of age was assessed via a non-inferiority analysis. Based on results for SARS-CoV-2 neutralizing titers at 28 days after Dose 2, the antibody levels generated by the vaccine in adolescents (N=340) was non-inferior to that found in young adults 18 to 25 years of age (N=305). The geometric mean titers ratio (GMR) of the adolescents to the young adults was 1.08, with a 2-sided 95% CI of 0.93 to 1.24; this value met the 1.5-fold non-inferiority criterion which was the lower bound of the 2-sided 95% CI for the GMR to be >0.67.

Overall, both solicited local and systemic adverse reactions (ARs) were more commonly reported by subjects in the vaccine group (approximately 2500 participants) than in the placebo group (approximately 1200 participants), and solicited systemic ARs generally increased after Dose 2. The majority of local and systemic solicited ARs were mild and moderate (grade 1 or grade 2). The majority of the solicited ARs in subjects who received the vaccine occurred within the first 1 to 2 days after any dose and generally persisted for a median of 1 to 3 days.

The most common solicited local ARs after Dose 1 and Dose 2 of vaccine were pain at injection site (93.1% and 92.4%, respectively), followed by axillary swelling/ tenderness (lymphadenopathy) (23.3% and 21.0%, respectively), swelling (16.2% and 20.5%, respectively), erythema (13.5% and 19.5%, respectively). Grade 3 solicited local ARs reported in ≥ 5% of subjects after Dose 1 and Dose 2 were pain (5.4% and 5.1% in the vaccine group vs < 0.1% and 0.2% in the placebo group, respectively).

The most common solicited systemic ARs after Dose 1 and Dose 2 were headache (44.6% and 70.2%, respectively), fatigue (47.9% and 67.8%, respectively), myalgia (26.9% and 46.6%, respectively), chills (18.4% and 43.0%, respectively) and fever (2.5% and 12.2%, respectively).

Grade 3 or higher solicited systemic ARs reported in ≥ 5% of subjects in the vaccine group and in the placebo group included fatigue (7.6% vs 0.8%, respectively) and myalgia (5.2% vs 0.2%, respectively) after Dose 2. Use of antipyretic or analgesic medications was 30.0% and 9.5% within 7 days post Dose 1, and 50.1% and 8.9% within 7 days post Dose 2 in the vaccine group and the placebo group, respectively.

Unsolicited treatment-emergent AEs (TEAE) up to 28 days after any dose were 20.5% (severe, 0.2%) in the vaccine group vs. 15.9% (severe, 0.1%) in the placebo group. Imbalances in unsolicited TEAEs up to 28 days after any dose observed in the vaccine group were primarily attributable to events related to local injection site reactions. No unsolicited severe TEAEs within 28 days of any dose were assessed by the investigators as related to the vaccine.

As of the data snapshot (May 8, 2021), the incidence of serious unsolicited adverse events (SAEs) was 0.2% in both groups during the overall study period. No SAEs were assessed by the investigators as related to the study vaccine. No deaths and no cases of multisystem inflammatory syndrome in children (MIS-C) were reported. No cases of myocarditis/pericarditis and Bells palsy were reported. No reports of anaphylactic reaction were assessed as related to the vaccine. No cases of severe COVID-19 were reported in the adolescents 12 to 17 years of age in the vaccine or the placebo groups.

Very rare cases of myocarditis and/or pericarditis following vaccination with mRNA vaccines have been reported during post-authorization use. The product monograph has been updated to include information on myocarditis and pericarditis. The Risk Management Plan (RMP) was also updated to include myocarditis and pericarditis as important identified risks. The risk will continue to be monitored closely.

The efficacy and immunogenicity of the COVID-19 Vaccine Moderna (mRNA-1273 SARS-CoV-2 vaccine) was demonstrated in individuals 12 to 17 years of age in Study P203. The efficacy was estimated to be 100% and is comparable to what was observed in adults. The safety data, with the median follow-up time 53 days after Dose 2 for all participants, and 942 (37.9%) subjects with at least 2-months (60 days) follow-up post Dose 2 in the vaccine group, indicated that the vaccine (100 µg dose) was well-tolerated.

Study P203 is ongoing and will continue to collect information on the long-term safety, efficacy and immunogenicity of the vaccine in adolescents up to 12 months after Dose 2. There are post-authorization commitments to monitor the long-term safety and efficacy of the vaccine for immunization in adolescents 12 to17 years of age. Based on the totality of the information, the benefit-risk profile of COVID-19 Vaccine Moderna is considered favorable for active immunization in individuals 12 to 17 years of age.

An updated RMP was included in the submission to expand the currently approved indication to children 12 to 17 years of age for the COVID-19 Vaccine Moderna. 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 for the adult indication, which included routine and additional pharmacovigilance activities, was considered to be acceptable for the expanded age group (12 to 17 years of age) with the addition of myocarditis and pericarditis as important identified risks. 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. Results related to safety and effectiveness from ongoing and planned studies will be submitted as they become available.

The COVID-19 Vaccine Moderna (mRNA-1273 SARS-CoV-2 vaccine) is therefore 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 to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 12 years of age and older.

Directions for use:

COVID-19 Vaccine Moderna should be administered intramuscularly, as two 0.5 mL doses, one month apart.

COVID-19 Vaccine Moderna is a suspension for intramuscular injection. A single dose is 0.5 mL.

For more information, refer to the Product Monograph for COVID-19 Vaccine Moderna.

Terms and Conditions:

Terms and conditions were imposed upon the authorization with respect to quality, clinical, labelling, and Risk Management Plan requirements.

Additional Terms and Conditions associated with the authorization for the indication to include use in individuals 12 to 17 years of age.

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