NUVAXOVID medication leaflet x10 INJECTION DISPERSION NOVAVAX CZ A.S.

J07BX03 COVID-19 vaccine (recombinant, with adjuvant)

Medicine NUVAXOVID contains substance COVID-19 vaccine (recombinant, with adjuvant) , ATC code J07BX03 - Antiinfectives for systemic use | Viral vaccines | Other viral vaccines .

General data about NUVAXOVID NOVAVAX CZ A.S.

Substance: COVID-19 vaccine (recombinant, with adjuvant)

Date of last drug list: 01-02-2022

Commercial code: W68339001

Pharmaceutical form: INJECTION DISPERSION

Quantity: 10

Product type: original

Prescription restrictions: P-RF - Medicines prescription that is retained in the pharmacy (not renewable).

Marketing authorisation

Manufacturer:NOVAVAX CZ A.S. - REPUBLICA CEHA

Holder: NOVAVAX CZ A.S. - REPUBLICA CEHA

Number: 1618/2021/01

Shelf life: 9 months-unopened bottle, at a temperature between (2°C - 8°C)

Contents of the package leaflet for the medicine NUVAXOVID x10 INJECTION DISPERSION NOVAVAX CZ A.S.

1. NAME OF THE MEDICINAL PRODUCT

Nuvaxovid dispersion for injection

COVID-19 Vaccine (recombinant, adjuvanted)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

This is a multidose vial which contains 10 doses of 0.5 mL

One dose (0.5 mL) contains 5 micrograms of the of SARS-CoV-2 spike protein* and is adjuvanted

with Matrix-M.

Adjuvant Matrix-M containing per 0.5 mL dose: Fraction-A (42.5 micrograms) and Fraction-C

(7.5 micrograms) of Quillaja saponaria Molina extract.

* 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.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Dispersion for injection (injection).

The dispersion is colourless to slightly yellow, clear to mildly opalescent (pH 7.2)

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Nuvaxovid is indicated for active immunisation to prevent COVID-19 caused by SARS-CoV-2 in

individuals 12 years of age and older.

The use of this vaccine should be in accordance with official recommendations.

4.2 Posology and method of administration

Posology
Primary vaccination series

Individuals 12 years of age and older
Nuvaxovid is administered intramuscularly as a course of 2 doses of 0.5 mL each. It is recommended

to administer the second dose 3 weeks after the first dose (see section 5.1).

Interchangeability

There are no data available on the interchangeability of Nuvaxovid with other COVID-19 vaccines to

complete the primary vaccination course. Individuals who have received a first dose of Nuvaxovid

should receive the second dose of Nuvaxovid to complete the vaccination course.

Booster dose
Booster dose in individuals 18 years of age and older

A booster dose of Nuvaxovid (0.5 mL) may be administered intramuscularly approximately 6 months

after the primary series of Nuvaxovid in individuals 18 years of age and older (homologous booster

dose).

Nuvaxovid may also be given as a booster dose in individuals 18 years of age and older following a

primary series comprised of an mRNA vaccine or adenoviral vector vaccine (heterologous booster

dose). The dosing interval for the heterologous booster dose is the same as that authorised for a

booster dose of the vaccine used for primary vaccination (see section 5.1).

Paediatric population
The safety and efficacy of Nuvaxovid in children aged less than 12 years have not yet been

established. No data are available.

Elderly population
No dose adjustment is required in elderly individuals ≥ 65 years of age.

Method of administration
Nuvaxovid is for intramuscular injection only, preferably into the deltoid muscle of the upper arm.

Do not inject the vaccine intravascularly, subcutaneously, or intradermally.

The vaccine should not be mixed in the same syringe with any other vaccines or medicinal products.

For precautions to be taken before administering the vaccine, see section 4.4.

For instructions on handling and disposal of the vaccine, see section 6.6.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number

of the administered product should be clearly recorded.

Hypersensitivity and anaphylaxis
Events of anaphylaxis have been reported with Nuvaxovid. Appropriate medical treatment and

supervision should always be readily available in case of an anaphylactic reaction following the

administration of the vaccine.

Close observation for at least 15 minutes is recommended following vaccination. A second dose of the

vaccine should not be given to those who have experienced anaphylaxis to the first dose of

Nuvaxovid.

Anxiety-related reactions
Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation, or stress‐related

reactions may occur in association with vaccination as a psychogenic response to the needle injection.

It is important that precautions are in place to avoid injury from fainting.

Concurrent illness
Vaccination should be postponed in individuals suffering from an acute severe febrile illness or acute

infection. The presence of a minor infection and/or low-grade fever should not delay vaccination.

Thrombocytopenia and coagulation disorders
As with other intramuscular injections, the vaccine should be given with caution in individuals

receiving anticoagulant therapy or those with thrombocytopenia or any coagulation disorder (such as

haemophilia) because bleeding or bruising may occur following an intramuscular administration in

these individuals.

Immunocompromised individuals
The efficacy, safety, and immunogenicity of the vaccine has been assessed in a limited number of

immunocompromised individuals. The efficacy of Nuvaxovid may be lower in immunosuppressed

individuals.

Duration of protection
The duration of protection afforded by the vaccine is unknown as it is still being determined by

ongoing clinical trials.

Limitations of vaccine effectiveness
Individuals may not be fully protected until 7 days after their second dose. As with all vaccines,

vaccination with Nuvaxovid may not protect all vaccine recipients.

Excipients
Sodium
This vaccine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-

free’.

Potassium
This vaccine contains potassium, less than 1 mmol (39 mg) per dose, that is to say, essentially

‘potassium-free’.

4.5 Interaction with other medicinal products and other forms of interaction

Co-administration of Nuvaxovid with inactivated influenza vaccines has been evaluated in a limited

number of participants in an exploratory clinical trial sub-study, see section 4.8 and section 5.1.

The binding antibody response to SARS-CoV-2 was lower when Nuvaxovid was given concomitantly

with inactivated influenza vaccine. The clinical significance of this is unknown.

Concomitant administration of Nuvaxovid with other vaccines has not been studied.

4.6 Fertility, pregnancy and lactation

Pregnancy
There is limited experience with use of Nuvaxovid in pregnant women. Animal studies do not indicate

direct or indirect harmful effects with respect to pregnancy, embryo/foetal development, parturition, or

post-natal development, see section 5.3.

Administration of Nuvaxovid in pregnancy should only be considered when the potential benefits

outweigh any potential risks for the mother and foetus.

Breast-feeding
It is unknown whether Nuvaxovid is excreted in human milk.

No effects on the breast-fed newborn/infant are anticipated since the systemic exposure of the breast-

feeding woman to Nuvaxovid is negligible.

Fertility
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity,

see section 5.3.

4.7 Effects on ability to drive and use machines

Nuvaxovid has no or negligible influence on the ability to drive and use machines. However, some of

the effects mentioned under section 4.8 may temporarily affect the ability to drive or use machines.

4.8 Undesirable effects

Summary of safety profile after two-dose primary series

Participants 18 years of age and older
The safety of Nuvaxovid was evaluated from an interim analysis of pooled data from 5 ongoing

clinical trials conducted in Australia, South Africa, the United Kingdom, the United States and

Mexico. At the time of the analysis, a total of 49,950 participants aged 18 years and older received at

least one dose of the two-dose primary series of Nuvaxovid (n=30,058) or placebo (n=19,892). At the

time of vaccination, the median age was 48 years (range 18 to 95 years). The median duration of

follow-up was 70 days post-Dose 2, with 32,993 (66%) participants completing more than 2 months

follow-up post-Dose 2.

Of the pooled reactogenicity data, which includes participants aged 18 years and older enrolled in the

two phase 3 studies who received any dose of Nuvaxovid (n=20,055) or placebo (n=10,561), the most

frequent adverse reactions were injection site tenderness (75%), injection site pain (62%), fatigue

(53%), myalgia (51%), headache (50%), malaise (41%), arthralgia (24%), and nausea or vomiting

(15%). Adverse reactions were usually mild to moderate in severity with a median duration of less

than or equal to 2 days for local events and less than or equal to 1 day for systemic events following

vaccination.

Overall, there was a higher incidence of adverse reactions in younger age groups: the incidence of

injection site tenderness, injection site pain, fatigue, myalgia, headache, malaise, arthralgia, and

nausea or vomiting was higher in adults aged 18 to less than 65 years than in those aged 65 years and

above.

Local and systemic adverse reactions were more frequently reported after Dose 2 than after Dose 1.

Licensed inactivated seasonal influenza vaccines were co-administered to participants on the same day

as Dose 1 of Nuvaxovid (n=217) or placebo (n=214) in the opposite deltoid muscle of the arm in 431

participants enrolled in an exploratory Phase 3 (2019nCoV-302) sub-study. The frequency of local and

systemic adverse reactions in the influenza sub-study population was higher than in the main study

population following Dose 1 in both Nuvaxovid and placebo recipients.

Adolescents 12 through 17 years of age
The safety of Nuvaxovid in adolescents was evaluated in an interim analysis of the paediatric

expansion portion of an ongoing Phase 3 multicentre, randomised, observer-blinded, placebo-

controlled study (Study 2019nCoV-301). Safety data were collected in 2,232 participants 12 through

17 years of age, with and without evidence of prior SARS CoV-2 infection, in United States who

received at least one dose of Nuvaxovid (n=1,487) or placebo (n=745). Demographic characteristics

were similar among participants who received Nuvaxovid and those who received placebo.

The most frequent adverse reactions were injection site tenderness (71%), injection site pain (67%),

headache (63%), myalgia (57%), fatigue (54%), malaise (43%), nausea or vomiting (23%), arthralgia

(19%) and pyrexia (17%). Fever was observed more frequently in adolescents aged 12 through to 17

years compared to adults, with the frequency being very common after the second dose in adolescents.

Adverse reactions were usually mild to moderate in severity with a median duration of less than or

equal to 2 days for local events and less than or equal to 1 day for systemic events following

vaccination.

Summary of safety profile after booster dose

Participants 18 years of age and older
The safety and immunogenicity of a booster dose of Nuvaxovid was evaluated in an ongoing Phase 2

randomised, placebo-controlled, observer-blinded clinical study (Study 2019nCoV-101, Part 2)

conducted in participants aged 18 to 84 years of age. A total of 254 participants received two doses of

Nuvaxovid (0.5 mL 3 weeks apart) as the primary vaccination series. A subset of 105 participants

(Safety Analysis Set) were randomised to receive a booster dose of Nuvaxovid approximately

6 months after receiving Dose 2 of the primary series and received at least 1 dose of study vaccine;

104 of the 105 participants received Nuvaxovid (Full Analysis Set). The median interval between the

second and the third doses was 165 days.

Solicited adverse reactions occurred at higher frequencies and with higher grade after the booster dose

than after the primary two-dose series. Persons who experienced severe reactions following the second

dose may be more likely to experience severe reactions following the third dose. The most frequent

solicited adverse reactions were injection site tenderness (81%), fatigue (63%), injection site pain

(55%), muscle pain (51%), malaise (47%) and headache (46%), joint pain (29%), and fever (17%)

with a median duration of 1 to 3 days following vaccination.

In an independent study (CoV-BOOST study, EudraCT 2021-002175-19) evaluating the use of a

Nuvaxovid booster dose in individuals who had completed primary vaccination with an authorised

mRNA COVID-19 vaccine or adenoviral vector COVID-19 vaccine, no new safety concerns were

identified.

Tabulated list of adverse reactions
Adverse reactions observed during clinical studies are listed below according to the following

frequency categories:

Very common (≥ 1/10),

Common (≥ 1/100 to < 1/10),

Uncommon (≥ 1/1,000 to < 1/100),

Rare (≥ 1/10,000 to < 1/1,000),

Very rare (< 1/10,000),

Not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1: Adverse reactions from Nuvaxovid clinical trials in individuals 12 years of age and

older

MedDRA System Very Common Uncommon Not known

Organ Class common (≥ 1/100 to (≥ 1/1,000 to (cannot be

(≥ 1/10) < 1/10) < 1/100) estimated from

the available

data)

Blood and Lymphadenopathy

lymphatic system

disorders

Immune system Anaphylaxis

disorders

Nervous system Headache Paraesthesia

disorders Hypoaesthesia

Vascular Hypertensiond

disorders
Gastrointestinal Nausea or

disorders vomitinga
Skin and Rash subcutaneous Erythema tissue disorders Pruritus

Urticaria

Musculoskeletal Myalgiaa

and connective Arthralgiaa tissue disorders
General disorders Injection site Injection site Injection site and tendernessa rednessa,c pruritus administration site Injection site Injection site conditions

paina swellinga

Fatiguea Pyrexiae
Malaisea,b Chills

Pain in

extremity

a Higher frequencies of these events were observed after the second dose.

b This term also included events reported as influenza-like illness

c This term includes both injection site redness and injection site erythema (common).

d Hypertension was not reported in adolescents aged 12 through 17 years in the clinical study.

e Pyrexia was observed more frequently in adolescents aged 12 through 17 years compared to adults, with the frequency

being very common after the second dose in adolescents.

Description of selected adverse reactions
Throughout the clinical trials, an increased incidence of hypertension following vaccination with

Nuvaxovid (n=46, 1.0%) as compared to placebo (n=22, 0.6%) was observed in older adults during

the 3 days following vaccination.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare

professionals are asked to report any suspected adverse reactions via the national reporting system

listed in Appendix V and include batch/Lot number if available.

4.9 Overdose

No case of overdose has been reported. In the event of an overdose, monitoring of vital functions and

possible symptomatic treatment is recommended.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Vaccine, other viral vaccines, ATC code: J07BX03

Mechanism of action
Nuvaxovid is composed of purified full-length SARS-CoV-2 recombinant spike (S) protein that is

stabilised in its prefusion conformation. The addition of the saponin-based Matrix-M adjuvant

facilitates activation of the cells of the innate immune system, which enhances the magnitude of the S

protein-specific immune response. The two vaccine components elicit B- and T-cell immune

responses to the S protein, including neutralising antibodies, which may contribute to protection

against COVID-19.

Clinical efficacy
The clinical efficacy, safety, and immunogenicity of Nuvaxovid is being evaluated in two pivotal,

placebo-controlled, Phase 3 studies, Study 1 (2019nCoV-301) conducted in North America and

Study 2 (2019nCoV-302) conducted in the United Kingdom, and a Phase 2a/b study, Study 3,

conducted in South Africa.

Study 1 (2019nCoV-301) - Two-Dose Primary Series

Study 1 is an ongoing Phase 3, multicentre, randomised, observer-blinded, placebo-controlled study

with an adult main study conducted in participants 18 years of age and older in the United States and

Mexico, and a paediatric expansion occurring in participants 12 through 17 years of age in the United

States.

Participants 18 years of age and older
Upon enrolment in the adult main study, participants were stratified by age (18 to 64 years and ≥ 65

years) and assigned in a 2:1 ratio to receive Nuvaxovid or placebo. The study excluded participants

who were significantly immunocompromised due to immunodeficiency disease; 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 comorbidity were

included as were participants with well-controlled HIV infection.

Enrolment of adults completed in February 2021. Participants will be followed for up to 24 months

after the second dose for assessments of safety, and efficacy against COVID-19. Following collection

of sufficient safety data to support application for emergency use authorisation, initial recipients of

placebo were invited to receive two injections of Nuvaxovid 21 days apart and initial recipients of

Nuvaxovid to receive two injections of placebo 21 days apart (“blinded crossover”). All participants

were offered the opportunity to continue to be followed in the study.

The primary efficacy analysis population (referred to as the Per-Protocol Efficacy [PP-EFF] analysis

set) included 25,452 participants who received either Nuvaxovid (n = 17,312) or placebo (n = 8,140),

received two doses (Dose 1 on day 0; Dose 2 at day 21, median 21 days [IQR 21-23], range 14-60),

did not experience an exclusionary protocol deviation, and did not have evidence of SARS-CoV-2

infection through 7 days after the second dose.

Demographic and baseline characteristics were balanced amongst participants who received

Nuvaxovid and those who received placebo. In the PP-EFF analysis set for participants who received

Nuvaxovid, the median age was 47 years (range: 18 to 95 years); 88% (n = 15,264) were 18 to

64 years old and 12% (n = 2,048) were aged 65 and older; 48% were female; 94% were from the

United States and 6% were from Mexico; 76% were White, 11% were Black or African American, 6%

were American Indian (including Native Americans) or Alaskan Native, and 4% were Asian; 22%

were Hispanic or Latino. At least one pre-existing comorbidity or lifestyle characteristic associated

with an increased risk of severe COVID-19 was present in 16,493 (95%) participants. Comorbidities

included: obesity (body mass index (BMI) ≥ 30 kg/m2); chronic lung disease; diabetes mellitus type 2,

cardiovascular disease; chronic kidney disease; or human immunodeficiency virus (HIV). Other high-

risk characteristics included age ≥65 years (with or without comorbidities) or age <65 years with

comorbidities and/or living or working conditions involving known frequent exposure to SARS-CoV-

2 or to densely populated circumstances.

COVID-19 cases were confirmed by polymerase chain reaction (PCR) through a central laboratory.

Vaccine efficacy is presented in Table 2.

Table 2: Vaccine efficacy against PCR-confirmed COVID-19 with onset from 7 days after

second vaccination 1 - PP-EFF analysis set; Study 2019nCoV-301

Nuvaxovid Placebo

Incidence Incidence

Partici- COVID- Rate Per Partici- COVID- Rate Per % Vaccine

pants 19 cases Year Per pants 19 cases Year Per Efficacy

Subgroup N n (%)2 1,000 N n (%)3 1,000 (95% CI)

People2 People2

Primary efficacy endpoint

All 17,312 14 (0.1) 3.26 8,140 63 (0.8) 34.01 90.4% participants (82.9, 94.6)3,4

1 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 up to 6 days after the second dose,

and who have received the full prescribed regimen of trial vaccine. 2 Mean disease incidence rate per year in 1,000 people. 3 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 - relative risk) (Zou 2004). 4 Met primary efficacy endpoint criterion for success with a lower bound confidence interval (LBCI) > 30%. at the planned

primary confirmatory analysis

Vaccine efficacy of Nuvaxovid to prevent the onset of COVID-19 from seven days after Dose 2 was

90.4% (95% CI 82.9,94.6). No cases of severe COVID-19 were reported in the 17,312 Nuvaxovid

participants compared with 4 cases of severe COVID-19 reported in the 8,140 placebo recipients in the

PP-EFF analysis set.

Subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates for male

and female participants and racial groups, and across participants with medical comorbidities

associated with high risk of severe COVID-19. There were no meaningful differences in overall

vaccine efficacy in participants who were at increased risk of severe COVID-19 including those with 1

or more comorbidities that increase the risk of severe COVID-19 (e.g., BMI ≥ 30 kg/m2, chronic lung

disease, diabetes mellitus type 2, cardiovascular disease, and chronic kidney disease).

Efficacy results reflect enrolment that occurred during the time period when strains classified as

Variants of Concern or Variants of Interest were predominantly circulating in the two countries (US

and Mexico) where the study was conducted. Sequencing data were available for 61 of the 77 endpoint

cases (79%). Of these, 48 out of 61 (79%) were identified as Variants of Concern or Variants of

Interest. The most common Variants of Concern identified were Alpha with 31/61 cases (51%), Beta

(2/61, 4%) and Gamma (2/61, 4%), while the most common Variants of Interest were Iota with 8/61

cases (13%), and Epsilon (3/61, 5%).

Efficacy in Adolescents 12 through 17 years of age

The assessment of efficacy and immunogenicity of Nuvaxovid in adolescent participants 12 through

17 years of age occurred in the United States in the ongoing paediatric expansion portion of the Phase

3 multicentre, randomised, observer-blinded, placebo-controlled 2019nCoV-301 study. A total of

1,799 participants, assigned in a 2:1 ratio to receive two doses of Nuvaxovid (n=1,205) or placebo

(n=594) by intramuscular injection 21 days apart, represented the Per Protocol Efficacy population.

Participants with confirmed infection or prior infection due to SARSCoV-2 at the time of

randomisation were not included in the primary efficacy analysis.

Enrolment of adolescents completed in June 2021. Participants will be followed for up to 24 months

after the second dose for assessments of safety, efficacy, and immunogenicity against COVID-19.

Following collection of a 60 days safety follow-up period, initial adolescent recipients of placebo were

invited to receive two injections of Nuvaxovid 21 days apart and initial recipients of Nuvaxovid to

receive two injections of placebo 21 days apart (“blinded crossover”). All participants were offered the

opportunity to continue to be followed in the study.

COVID-19 was defined as first episode of PCR-confirmed mild, moderate, or severe COVID-19 with

at least one or more of the predefined symptoms within each severity category. Mild COVID-19 was

defined as fever, new onset cough or at least 2 or more additional COVD-19 symptoms.

There were 20 cases of PCR-confirmed symptomatic mild COVID-19 (Nuvaxovid, n=6 [0.5%];

placebo, n=14 [2.4%]) resulting in a point estimate of efficacy of 79.5% (95% CI: 46.8%, 92.1%).

At the time of this analysis, the Delta (B.1.617.2 and AY lineages) variant of concern (VOC) was the

predominant variant circulating in the US and accounted for all cases from which sequence data are

available (11/20, 55%).

Immunogenicity in Adolescents 12 through 17 years of age An analysis of the SARS-CoV-2

neutralising antibody response 14 days after Dose 2 (Day 35) was conducted in adolescent participants

seronegative to anti-SARS-CoV-2 nucleoprotein (NP) and PCR-negative at baseline. Neutralising

antibody responses were compared with those observed in seronegative/PCR-negative adult

participants aged 18 through 25 years from the adult main study (Per Protocol Immunogenicity (PP-

IMM) Analysis Set) as shown in Table 3. Noninferiority required that the following three criteria were

met: lower bound of two-sided 95% CI for the ratio of geometric mean titers (GMTs) (GMT 12

through 17 years/GMT 18 through 25 years) > 0.67; point estimate of the ratio of GMTs ≥ 0.82; and

the lower bound of the two-sided 95% CI for difference of seroconversion rates (SCRs) (SCR 12

through 17 years minus SCR 18 through 25 years) > -10%. These noninferiority criteria were met.

Table 3 : Adjusted Ratio of Geometric Mean of Microneutralisation Assay Neutralising Antibody

Titers for SARS-CoV-2 S Wild-Type Virus at Day 35 Overall and Presented by Age Group (PP-

IMM Analysis Set)1

Pediatric Expansion Adult Main Study 12 through 17 (12 through 17 Years) (18 through 25 Years) Years

Timepoint versus

Assay N=390 N=416 18 through 25

Years

GMT GMT GMR 95% CI2 95% CI2 95% CI2

Microneutralisation Day 35 (14 3859.6 2633.6 1.46 (1/dilution) days after (3422.8, 4352.1) (2388.6, 2903.6) (1.25, 1.71)3

Dose 2)

Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; GMR = ratio of GMT, which is defined as the

ratio of 2 GMTs for comparison of 2 age cohorts; GMT = geometric mean titer; LLOQ = lower limit of quantitation; MN =

microneutralisation; N = number of participants in assay-specific PP-IMM Analysis Set in each part of study with non-

missing response at each visit; PP-IMM = Per-Protocol Immunogenicity; SARS-CoV-2 = severe acute respiratory syndrome

coronavirus2. 1 Table includes participants in the active vaccine group only. 2 An ANCOVA with age cohort as main effect and baseline MN Assay neutralising antibodies as covariate was performed

to estimate the GMR. Individual response values recorded as below the LLOQ were set to half LLOQ.

3 Represents (n1, n2) populations defined as:

n1 = number of participants in adult main study (18 through 25 years) with non-missing neutralising antibodies result

n2 = number of participants in paediatric expansion (12 through 17 years) with non-missing neutralising antibodies result

Study 2 (2019nCoV-302) - Two-Dose Primary Series

Study 2 is an ongoing Phase 3, multicentre, randomised, observer-blinded, placebo-controlled study in

participants 18 to 84 years of age in the United Kingdom. Upon enrolment, participants were stratified

by age (18 to 64 years; 65 to 84 years) to receive Nuvaxovid or placebo. The study excluded

participants who were significantly immunocompromised due to immunodeficiency disease; current

diagnosis or treatment for cancer; autoimmune disease/condition; received chronic

immunosuppressive therapy or received immunoglobulin or blood-derived products within 90 days;

bleeding disorder or continuous use of anticoagulants; history of allergic reactions and/or anaphylaxis;

were pregnant; or had a history of laboratory-confirmed diagnosed COVID-19. Participants with

clinically stable disease, defined as disease not requiring significant change in therapy or

hospitalisation for worsening disease during the 4 weeks before enrolment were included. Participants

with known stable infection with HIV, hepatitis C virus (HCV), or hepatitis B virus (HBV) were not

excluded from enrolment.

Enrolment was completed in November 2020. Participants are being followed for up to 12 months

after the primary vaccination series for assessments of safety and efficacy against COVID-19.

The primary efficacy analysis set (PP-EFF) included 14,039 participants who received either

Nuvaxovid (n=7,020) or placebo (n=7,019), received two doses (Dose 1 on day 0; Dose 2 at median

21 days (IQR 21-23), range 16-45, did not experience an exclusionary protocol deviation, and did not

have evidence of SARS-CoV-2 infection through 7 days after the second dose.

Demographic and baseline characteristics were balanced amongst participants who received

Nuvaxovid and participants who received placebo. In the PP-EFF analysis set for participants who

received Nuvaxovid, median age was 56.0 years (range: 18 to 84 years); 72% (n=5,067) were 18 to

64 years old and 28% (n=1,953) were aged 65 to 84; 49% were female; 94% were White; 3% were

Asian; 1% were multiple races, <1% were Black or African American; and <1% were Hispanic or

Latino; and 45% had at least one comorbid condition.

Table 4: Vaccine efficacy analysis of PCR-confirmed COVID-19 with onset at least 7 days after

the second vaccination - (PP-EFF population): Study 2 (2019nCoV-302)

Nuvaxovid Placebo

Incidence Incidence

Partici- COVID- Rate Per Partici- COVID- Rate Per % Vaccine

pants 19 cases Year Per pants 19 cases Year Per Efficacy

Subgroup N n (%) 1,000 N n (%) 1,000 (95% CI)

People1 People1

Primary efficacy endpoint

All 89.7% participants 7,020 10 (0.1) 6.53 7,019 96 (1.4) 63.43

(80.2, 94.6)2, 3

Subgroup analyses of the primary efficacy endpoint

18 to 64 89.8%

years of 5,067 9 (0.2) 12.30 5,062 87 (1.7) 120.22 (79.7, 94.9)2

age

65 to 84 88.9%

years of 1,953 1 (0.10)2 --- 1,957 9 (0.9)2 --- (20.2, 99.7)4

age

1 Mean disease incidence rate per year in 1000 people. 2 Based on Log-linear model of occurrence using modified Poisson regression with logarithmic link function, treatment

group and strata (age-group and pooled region) as fixed effects and robust error variance [Zou 2004]. 3 Met primary efficacy endpoint criterion for success with a lower bound confidence interval (LBCI) > 30%, efficacy has

been confirmed at the interim analysis. 4 Based on the Clopper-Pearson model (due to few events), 95% CIs calculated using the Clopper-Pearson exact binomial

method adjusted for the total surveillance time.

These results reflect enrolment that occurred during the time period when the B.1.1.7 (Alpha) variant

was circulating in the UK. Identification of the Alpha variant was based on S gene target failure by

PCR. Data were available for 95 of the 106 endpoint cases (90%). Of these, 66 out of 95 (69%) were

identified as the Alpha variant with the other cases classified as non-Alpha.

No cases of severe COVID-19 were reported in the 7,020 Nuvaxovid participants compared with 4

cases of severe COVID-19 reported in the 7,019 placebo recipients in the PP-EFF analysis set.

Licensed seasonal influenza vaccine co-administration sub-study
Overall, 431 participants were co-vaccinated with inactivated seasonal influenza vaccines; 217 sub-

study participants received Nuvaxovid and 214 received placebo. Demographic and baseline

characteristics were balanced amongst participants who received Nuvaxovid and participants who

received placebo. In the per-protocol immunogenicity (PP-IMM) analysis set for participants who

received Nuvaxovid (n=191), median age was 40 years (range: 22 to 70 years); 93% (n=178) were 18

to 64 years old and 7% (n=13) were aged 65 to 84; 43% were female; 75% were White; 23% were

multiracial or from ethnic minorities; and 27% had at least one comorbid condition. Co-administration

resulted in no change to influenza vaccine immune responses as measured by hemagglutination

inhibition (HAI) assay. A 30% reduction in antibody responses to Nuvaxovid was noted as assessed by

an anti-spike IgG assay with seroconversion rates similar to participants who did not receive

concomitant influenza vaccine (see section 4.5 and section 4.8).

Study 3 (2019nCoV-501) - Two-Dose Primary Series

Study 3 is an ongoing Phase 2a/b, multicentre, randomised, observer-blinded, placebo-controlled study

in HIV-negative participants 18 to 84 years of age and people living with HIV (PLWH) 18 to 64 years

of age in South Africa. PLWH were medically stable (free of opportunistic infections), receiving

highly active and stable antiretroviral therapy, and having an HIV-1 viral load of < 1000 copies/mL.

Enrolment was completed in November 2020.

The primary efficacy analysis set (PP-EFF) included 2,770 participants who received either

Nuvaxovid (n=1,408) or placebo (n=1,362), received two doses (Dose 1 on day 0; Dose 2 on day 21),

did not experience an exclusionary protocol deviation, and did not have evidence of SARS-CoV-2

infection through 7 days after the second dose.

Demographic and baseline characteristics were balanced amongst participants who received

Nuvaxovid and participants who received placebo. In the PP-EFF analysis set for participants who

received Nuvaxovid, median age was 28 years (range: 18 to 84 years); 40% were female; 91% were

Black/African American; 2% were White; 3% were multiple races, 1% were Asian; and 2% were

Hispanic or Latino; and 5.5% were HIV-positive.

A total of 147 symptomatic mild, moderate, or severe COVID-19 cases among all adult participants,

seronegative (to SARS-CoV-2) at baseline, were accrued for the complete analysis (PP-EFF Analysis

Set) of the primary efficacy endpoint, with 51 (3.62%) cases for Nuvaxovid versus 96 (7.05%) cases

for placebo. The resultant vaccine efficacy of Nuvaxovid was 48.6% (95% CI: 28.4, 63.1).

These results reflect enrolment that occurred during the time period when the B.1.351 (Beta) variant

was circulating in South Africa.

Immunogenicity in participants 18 years of age and older - after booster dose

The safety and immunogenicity of a booster dose of Nuvaxovid was evaluated in an ongoing Phase 2

randomised, observer-blinded, placebo-controlled clinical study administered as a single booster dose

(Study 2019nCoV-101, Part 2) in healthy adult participants aged 18 to 84 years of age who were

seronegative to SARS-CoV-2 at baseline. A total of 254 participants (Full Analysis Set) received two

doses of Nuvaxovid (0.5 mL, 5 micrograms 3 weeks apart) as the primary vaccination series. A subset

of 104 participants received a booster dose of Nuvaxovid approximately 6 months after receiving

Dose 2 of the primary series. A single booster dose of Nuvaxovid induced an. approximate 96-fold

increase in neutralising antibodies from a GMT of 63 pre-booster (Day 189) to a GMT of 6,023 post-

booster (Day 217) and an approximate 4.1-fold increase from a peak GMT (14 days post-Dose 2) of

1,470.

In Study 3, an ongoing Phase 2a/b randomised, observer-blinded, placebo-controlled study, the safety

and immunogenicity of booster dose was evaluated in healthy HIV-negative adult participants 18 to

84 years of age and medically stable PLWH 18 to 64 years of age who were seronegative to SARS-

CoV-2 at baseline. A total of 1,173 participants (PP-IMM Analysis Set) received a booster dose of

Nuvaxovid approximately 6 months after completion of the primary series of Nuvaxovid (Day 201).

An approximate 52-fold increase in neutralising antibodies was shown from a GMT of 69 pre-booster

(Day 201) to a GMT of 3,600 post-booster (Day 236) and an approximate 5.2-fold increase from a

peak GMT (14 days post-Dose 2) of 694.

Safety and immunogenicity of COVID-19 vaccines given as a third dose (booster) following

completion of a primary vaccination series with another authorised COVID-19 vaccine in the UK

An independent, multicentre, randomised, controlled, Phase 2 investigator-initiated trial (CoV-

BOOST, EudraCT 2021-002175-19) investigated the immunogenicity of a third dose (booster) in

adults aged 30 years and older with no history of laboratory-confirmed SARS-CoV-2 infection.

Nuvaxovid was administered at least 70 days after completion of a ChAdOx1 nCov-19 (Oxford-

AstraZeneca) primary vaccination series or at least 84 days after completion of a BNT162b2 (Pfizer-

BioNtech) primary vaccination series. Neutralising antibody titers measured by a wild-type assay were

assessed 28 days post-booster dose. Within the group assigned to receive Nuvaxovid, 115 participants

received a two-dose primary series of ChAdOx1 nCov-19 and 114 participants received a two-dose

primary series of BNT162b2, prior to receiving a single booster dose (0.5 mL) of Nuvaxovid. The

Novavax COVID-19 Vaccine, Adjuvanted demonstrated a booster response regardless of the vaccine

used for primary vaccination.

Elderly population
Nuvaxovid was assessed in individuals 18 years of age and older. The efficacy of Nuvaxovid was

consistent between elderly (≥ 65 years) and younger individuals (18 to 64 years).

Paediatric population
The European Medicines Agency has deferred the obligation to submit the results of studies with

Nuvaxovid in one or more subsets of the paediatric population in prevention of COVID-19, see section

4.2 for information on paediatric use.

Conditional approval
This medicinal product has been authorised under a so-called ‘conditional approval’ scheme. This

means that further evidence on this medicinal product is awaited. The European Medicines Agency

will review new information on this medicinal product at least every year and this SmPC will be

updated as necessary.

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of repeat-dose

toxicity, local tolerance and reproductive and developmental toxicity.

Genotoxicity and Carcinogenicity

In vitro genotoxicity studies were conducted with the Matrix-M adjuvant. The adjuvant was shown to

be non-genotoxic. Carcinogenicity studies were not performed. Carcinogenicity is not expected.

Reproductive toxicity
A developmental and reproductive toxicity study was performed in female rats administered four

intramuscular doses (two prior to mating; two during gestation) of 5 micrograms SARS-CoV-2 rS

protein (approximately 200-fold excess relative to the human dose of 5 micrograms on a weight-

adjusted basis) with 10 micrograms Matrix-M adjuvant (approximately 40-fold excess relative to the

human dose of 50 micrograms on a weight-adjusted basis). No vaccine-related adverse effects on

fertility, pregnancy/lactation, or development of the embryo/foetus and offspring through post-natal

Day 21 were observed.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Disodium hydrogen phosphate heptahydrate

Sodium dihydrogen phosphate monohydrate

Sodium chloride

Polysorbate 80

Sodium hydroxide (for adjustment of pH)

Hydrochloric acid (for adjustment of pH)

Water for injections

Adjuvant (Matrix-M)
Cholesterol

Phosphatidylcholine (including all-rac-α-Tocopherol)
Potassium dihydrogen phosphate
Potassium chloride
Disodium hydrogen phosphate dihydrate
Sodium chloride
Water for injections

For adjuvant: see also section 2.

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products or diluted.

6.3 Shelf life

Unopened vial
9 months at 2°C to 8°C, protected from light.

Unopened Nuvaxovid vaccine has been shown to be stable up to 12 hours at 25°C. Storage at 25°C is

not the recommended storage or shipping condition but may guide decisions for use in case of

temporary temperature excursions during the 9-month storage at 2°C to 8°C.

Punctured vial
Chemical and physical in-use stability has been demonstrated for 6 hours at 2°C to 25°C from the time

of first needle puncture to administration.

From a microbiological point of view, after first opening (first needle puncture), the vaccine should be

used immediately. If not used immediately, in-use storage times and conditions are the responsibility

of the user.

6.4 Special precautions for storage

Store in a refrigerator (2°C - 8°C).

Do not freeze.

Keep the vials in the outer carton in order to protect from light.

For storage conditions after first opening of the medicinal product, see section 6.3.

6.5 Nature and contents of container

5 mL of dispersion in a vial (type I glass) with a stopper (bromobutyl rubber) and an aluminium

overseal with blue plastic flip-off cap.

Each vial contains 10 doses of 0.5 mL.

Pack size: 10 multidose vials

6.6 Special precautions for disposal and other handling

Handling instructions and administration
This vaccine should be handled by a healthcare professional using aseptic techniques to ensure the

sterility of each dose.

Preparation for use:

* The vaccine comes ready to use.

* Unopened vaccine should be stored at 2°C to 8°C and kept within the outer carton to protect

from light.

* Immediately prior to use, remove the vaccine vial from the carton in the refrigerator.

* Record the date and time of discard on the vial label. Use within 6 hours after first puncture.

Inspect the vial:

* Gently swirl the multidose vial before and in between each dose withdrawal. Do not shake.

* Each multidose vial contains a colourless to slightly yellow, clear to mildly opalescent

dispersion free from visible particles.

* Visually inspect the contents of the vial for visible particulate matter and/or discolouration

prior to administration. Do not administer the vaccine if either are present.

Administer the vaccine:

* An overfill is included per vial to ensure that a maximum of ten (10) doses of 0.5 mL each can

be extracted.

* Each 0.5 mL dose is withdrawn into a sterile needle and sterile syringe to be administered by

intramuscular injection, preferably in the deltoid muscle of the upper arm.

* Do not mix the vaccine in the same syringe with any other vaccines or medicinal

products.

* Do not pool excess vaccine from multiple vials.

Storage after first needle puncture:

* Nuvaxovid does not contain a preservative. Store the opened vial between 2°C to 25°C for up

to 6 hours after first puncture, see section 6.3.

Discard:

* Discard this vaccine if not used within 6 hours after first puncture of the vial, see section 6.3.

Disposal:
* Any unused medicinal product or waste material should be disposed of in accordance with

local requirements.

7. MARKETING AUTHORISATION HOLDER

Novavax CZ a.s.

Bohumil 138

Jevany, 28163

Czechia

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/21/1618/001

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 20th December 2021

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines

Agency http://www.ema.europa.eu.