NOVAVAX COVID-19 Vaccine, Adjuvanted: Package Insert and Label Information (Page 3 of 5)

6.2 Post-Authorization Experience

The following adverse reactions have been identified during post-authorization use of the Novavax COVID-19 Vaccine, Adjuvanted. Because these reactions are reported voluntarily, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure.

Cardiac Disorders: myocarditis, pericarditis

Immune System Disorders: anaphylaxis

Nervous System Disorders: paresthesia, hypoesthesia

8 REQUIREMENTS AND INSTRUCTIONS FOR REPORTING ADVERSE EVENTS AND VACCINE ADMINISTRATION ERRORS

See Overall Safety Summary (Section 6) for additional information.

The vaccination provider enrolled in the federal COVID-19 Vaccination Program is responsible for MANDATORY reporting of the listed events following the Novavax COVID-19 Vaccine, Adjuvanted to the Vaccine Adverse Event Reporting System (VAERS):

  • Vaccine administration errors whether or not associated with an adverse event
  • Serious adverse events* (irrespective of attribution to vaccination)
  • Cases of myocarditis,
  • Cases of pericarditis,
  • Cases of Multisystem Inflammatory Syndrome (MIS) in adults and children
  • Cases of COVID-19 that result in hospitalization or death

*Serious adverse events are defined as:

  • Death;
  • A life-threatening adverse event;
  • Inpatient hospitalization or prolongation of existing hospitalization;
  • A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions;
  • A congenital anomaly/birth defect;
  • An important medical event that based on appropriate medical judgement may jeopardize the individual and may require medical or surgical intervention to prevent one of the outcomes listed above.

Instructions for Reporting to VAERS

The vaccination provider enrolled in the federal COVID-19 Vaccination Program should complete and submit a VAERS form to FDA using one of the following methods:

  • Complete and submit the report online: https://vaers.hhs.gov/reportevent.html, or
  • If you are unable to submit this form electronically, you may fax it to VAERS at 1-877-721-0366. If you need additional help submitting a report, you may call the VAERS toll-free information line at 1-800-822-7967 or send an email to info@vaers.org.

IMPORTANT: When reporting adverse events or vaccine administration errors to VAERS, please complete the entire form with detailed information. It is important that the information reported to the FDA be as detailed and as complete as possible. Information to include:

  • Patient demographics (e.g., patient name, date of birth)
  • Pertinent medical history
  • Pertinent details regarding admission and course of illness
  • Concomitant medications
  • Timing of adverse event(s) in relationship to administration of the Novavax COVID-19 Vaccine, Adjuvanted
  • Pertinent laboratory and virology information
  • Outcome of the event and any additional follow-up information if it is available at the time of the VAERS report. Subsequent reporting of follow-up information should be completed if additional details become available.

The following steps are highlighted to provide the necessary information for safety tracking:

  1. In Box 17, provide information on the Novavax COVID-19 Vaccine, Adjuvanted and any other vaccines administered on the same day; and in Box 22, provide information on any other vaccines received within one month prior.
  2. In Box 18, description of the event:
    1. Write “Novavax COVID-19 Vaccine, Adjuvanted EUA” as the first line.
    2. Provide a detailed report of vaccine administration error and/or adverse event. It is important to provide detailed information regarding the patient and adverse event/medication error for ongoing safety evaluation of this unapproved vaccine. Please see information to include listed above.
  3. Contact information:
    1. In Box 13, provide the name and contact information of the prescribing healthcare provider or institutional designee who is responsible for the report.
    2. In Box 14, provide the name and contact information of the best doctor/healthcare professional to contact about the adverse event.
    3. In Box 15, provide the address of the facility where vaccine was given (NOT the healthcare provider’s office address).

Other Reporting Instructions

Vaccination providers may report to VAERS other adverse events that are not required to be reported using the contact information above.

To the extent feasible, report adverse events to Novavax, Inc. using the contact information below or by providing a copy of the VAERS form to Novavax, Inc.

Website

Fax number

Telephone number

www.NovavaxMedInfo.com

1-888-988-8809

1-844-NOVAVAX(1-844-668-2829)

10 DRUG INTERACTIONS

There is no information on co-administration of the Novavax COVID-19 Vaccine, Adjuvanted with other vaccines.

11 USE IN SPECIFIC POPULATIONS

11.1 Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to the Novavax COVID-19 Vaccine, Adjuvanted during pregnancy. Women who are vaccinated with the Novavax COVID-19 Vaccine, Adjuvanted during pregnancy are encouraged to enroll in the registry by visiting https://c-viper.pregistry.com/.

Risk Summary

All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Available data on the Novavax COVID-19 Vaccine, Adjuvanted administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

In a developmental toxicity study, 0.1 mL of a vaccine formulation containing the same quantity of SARS-CoV-2 rS protein (5 mcg), one-fifth the quantity of adjuvant (10 mcg) and inactive ingredients which comprise the formulation buffer (25mM sodium phosphate, 300mM sodium chloride, and 0.01% (w/v) polysorbate 80) contained in a single dose of the Novavax COVID-19 Vaccine, Adjuvanted was administered to female rats by the intramuscular route on four occasions: 27 and 13 days prior to mating, and on gestational days 7 and 15. No vaccine-related adverse effects on female fertility, fetal development or postnatal development were reported in the study.

11.2 Lactation

Risk Summary

Data are not available to assess the effects of the Novavax COVID-19 Vaccine, Adjuvanted on the breastfed infant or on milk production/excretion.

11.3 Pediatric Use

Emergency Use Authorization of Novavax COVID-19 Vaccine, Adjuvanted in adolescents 12 through 17 years of age is based on safety and effectiveness data in this age group and in adults.

The Novavax COVID-19 Vaccine, Adjuvanted is not authorized for use in individuals younger than 12 years of age.

11.4 Geriatric Use

Clinical studies of the Novavax COVID-19 Vaccine, Adjuvanted included participants 65 years of age and older receiving vaccine or placebo, and their data contribute to the overall assessment of safety and efficacy. In an ongoing Phase 3 clinical study (Study 1), 12.6% (n=2,480 Novavax COVID-19 Vaccine, Adjuvanted, n=1,235 placebo) of participants were 65 years of age and older and 1.8% (n=361 Novavax COVID-19 Vaccine, Adjuvanted, n=179 placebo) of participants were 75 years of age and older. Vaccine efficacy in participants 65 years of age and older was 78.6% (95% CI: -16.6%, 96.1%) relative to 90.7% (95% CI: 72.9%, 96.8%) in participants 50 through 64 years of age. [see Clinical Trial Results and Supporting Data for EUA (18.1)]. Overall, there were no notable differences in the safety profiles observed between participants 65 years of age and older and younger participants. [see Overall Safety Summary (6)]

13 DESCRIPTION

The Novavax COVID-19 Vaccine, Adjuvanted is a colorless-to-slightly yellow, clear-to-mildly opalescent suspension for intramuscular injection that is free from visible particles. Each 0.5 mL dose of the Novavax COVID-19 Vaccine, Adjuvanted contains 5 mcg of SARS-CoV-2 recombinant spike (rS) protein and 50 mcg Matrix-M adjuvant. The Matrix-M adjuvant is composed of Fraction-A (42.5 mcg) and Fraction-C (7.5 mcg) of saponin extracts from the soapbark tree, Quillaja saponaria Molina.

The rS protein is produced by recombinant DNA technology using a baculovirus expression system in an insect cell line that is derived from Sf9 cells of the Spodoptera frugiperda species.

Each dose of the Novavax COVID-19 Vaccine, Adjuvanted also contains the following ingredients: cholesterol, phosphatidylcholine, potassium dihydrogen phosphate (3.85 mcg), potassium chloride (2.25 mcg), disodium hydrogen phosphate dihydrate (14.7 mcg), disodium hydrogen phosphate heptahydrate (2.465 mg), sodium dihydrogen phosphate monohydrate (0.445 mg), sodium chloride (8.766 mg) and polysorbate 80 (0.050 mg), and Water for Injection. The pH is adjusted with sodium hydroxide or hydrochloric acid.

Each 0.5 mL dose of the Novavax COVID-19 Vaccine, Adjuvanted may also contain residual amounts of baculovirus and Sf9 cell proteins (≤ 0.96 mcg), baculovirus and cellular DNA (≤ 0.00016 mcg), lentil lectin (< 0.025 mcg), methyl-α-D-mannopyranoside (2 mcg), simethicone (<0.92 mcg), pluronic F-68 (< 2.19 mcg), Triton X-100 (< 0.025 mcg), and Tergitol (NP9) (< 0.05 mcg).

The Novavax COVID-19 Vaccine, Adjuvanted does not contain preservative.

The vial stoppers are not made with natural rubber latex.

14 CLINICAL PHARMACOLOGY

14.1 Mechanism of Action

The Novavax COVID-19 Vaccine, Adjuvanted contains purified, full-length rS protein. The vaccine elicits an immune response to the rS protein, which protects against COVID-19.

18 CLINICAL TRIAL RESULTS AND SUPPORTING DATA FOR EUA

18.1 Efficacy in Participants 18 Years of Age and Older

Study 1 is an ongoing Phase 3, multicenter, randomized, observer-blinded, placebo-controlled study in participants 18 years of age and older in United States and Mexico.

Upon enrollment, participants were stratified by age (18 through 64 years or 65 years of age and older). The study excluded participants who were significantly immunocompromised due to immunodeficiency disease; had active cancer on chemotherapy; received chronic immunosuppressive therapy or received immunoglobulin or blood-derived products within 90 days; were pregnant or breastfeeding; or had a history of laboratory-confirmed diagnosed COVID-19. Participants with clinically stable underlying comorbidities were included as were participants with well-controlled human immunodeficiency virus (HIV) infection.

A total of 29,945 participants were randomized in a 2:1 ratio to receive two doses of the Novavax COVID-19 Vaccine, Adjuvanted or placebo 3 weeks apart. Assessments of safety and efficacy against COVID-19 are planned for up to 24 months after the second dose.

The primary efficacy analysis population (Per Protocol Efficacy [PP-EFF] Analysis Set) included 25,657 participants who received either the Novavax COVID-19 Vaccine, Adjuvanted (n=17,272) or placebo (n=8,385), received two doses (Dose 1 on day 0; Dose 2 on day 21 median 21 days, range 14-60), did not experience an exclusionary protocol deviation, and did not have evidence of SARS-CoV-2 infection through 6 days after the second dose. In the PP-EFF Analysis Set, 48.5% were female; 21.5% were Hispanic or Latino; 75.9% were White, 11.0% were Black or African American, 6.2% were American Indian or Alaska Native, 4.4% were Asian, and 1.7% were multiracial. The median age of participants was 47 years (range 18-95 years) and 11.7% were 65 years of age and older. Of the study participants in the PP-EFF Analysis Set, 95.2% were at high risk for COVID-19 due to living or working conditions involving known frequent exposure to SARS-CoV-2, comorbidities (chronic lung disease, cardiovascular disease, chronic liver disease, severe obesity, and diabetes), or age ≥ 65 years. Between participants who received the Novavax COVID-19 Vaccine, Adjuvanted and those who received placebo, there were no notable differences in demographics or pre-existing medical conditions. Participants in the PP-EFF Analysis Set were included in the primary efficacy analysis up until the time that they received their crossover vaccination. As of the September 27, 2021, data cutoff date, the PP-EFF Analysis Set had a median follow-up of 2.5 months post-Dose 2 during the pre-crossover period.

Efficacy of a Primary Series in Participants 18 Years of Age and Older

Vaccine efficacy in participants without evidence of SARS-CoV-2 infection through 6 days after the second dose is presented in Table 4. Based on data accrued through September 27, 2021, the efficacy of the Novavax COVID-19 Vaccine, Adjuvanted to prevent polymerase chain reaction (PCR)-confirmed symptomatic mild, moderate or severe COVID-19 from 7 days after Dose 2 was 90.4% (95% CI: 83.8%, 94.3%). In the PP-EFF Analysis Set, no cases of moderate or severe COVID-19 were reported in participants who had received the Novavax COVID-19 Vaccine, Adjuvanted, compared with nine cases of moderate COVID-19 and four cases of severe COVID-19 reported in participants who had received placebo.

Table 4 Vaccine Efficacy Against PCR-confirmed COVID-19 with Onset from 7 Days After Second Vaccination * (PP-EFF Analysis Set)
Subgroup Novavax COVID-19 Vaccine, Adjuvanted Placebo Vaccine Efficacy (95% CI) (%)
Partici-pantsN COVID-19 Casesn (%) Mean Incidence Rate Per 1,000 Person-Years Partici-pantsN COVID-19 Casesn (%) Mean Incidence Rate Per 1,000 Person-Years
*
Vaccine efficacy (VE) evaluated in participants without major protocol deviations who are seronegative (for SARS-CoV-2) at baseline and do not have a laboratory confirmed current SARS-CoV-2 infection with symptom onset through 6 days after the second dose, and who have received two doses of vaccine or placebo as randomized.
Mean incidence rate per 1,000 person-years was estimated with weighting for age strata reflective of the distribution seen in the study population.
Based on log-linear model of PCR-confirmed COVID-19 infection incidence rate using Poisson regression with treatment group and age strata as fixed effects and robust error variance, where VE = 100 × (1 – ratio of incidence rate) (Zou 2004).
§
Met primary efficacy endpoint criterion for success with a lower bound confidence interval (LBCI) >30% at the planned primary confirmatory analysis.
Primary efficacy endpoint
All participants 17,272 17 (0.1) 5.59 8,385 79 (0.9) 58.30 90.4(83.8, 94.3) , §
Mild 17 (0.1) 66 (0.8)
Moderate 0 9 (0.1)
Severe 0 4 (< 0.1)

Descriptive analyses of efficacy showed efficacy point estimates similar to the estimate for the overall study population across genders and racial groups, and across participants with or without medical comorbidities associated with high risk of severe COVID-19. Vaccine efficacy in participants of Hispanic/Latino ethnicity was 77.0% (95% CI: 48.7%, 89.7%) relative to 94.2% (95% CI: 87.9%, 97.2%) in participants who were not Hispanic/Latino. Vaccine efficacy in participants 65 years of age and older was 78.6% (95% CI: -16.6%, 96.1%) relative to 90.7% (95% CI: 72.9%, 96.8%) in participants 50 through 64 years of age.

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