COMIRNATY COVID-19 VACCIN 30mcg / dose concentrate for injection dispersion medication leaflet

Comirnaty Omicron XBB.1.5 30 micrograms/dose dispersion for injection

Comirnaty Omicron XBB.1.5 30 micrograms/dose dispersion for injection in pre-filled syringe

Comirnaty Omicron XBB.1.5 10 micrograms/dose dispersion for injection

COVID−19 mRNA Vaccine

Do not dilute prior to use.

Table 1. Comirnaty Omicron XBB.1.5 qualitative and quantitative composition

Dose(s) per container

Product presentation Container (see sections 4.2 and 6.6) Contents per dose

Single dose One dose (0.3 mL)

Comirnaty Omicron XBB.1.5 vial 1 dose of 0.3 mL30 micrograms/dose dispersion (grey cap) contains

Multidose 30 micrograms offor injection (2.25 mL) vial 6 doses of 0.3 mL raxtozinameran, a(grey cap) COVID-19 mRNA

Comirnaty Omicron XBB.1.5 Vaccine (nucleoside30 micrograms/dose dispersion Pre-filled modified, embeddedfor injection in pre-filled syringe 1 dose of 0.3 mL in lipidsyringe nanoparticles).

Single dose One dose (0.3 mL)vial 1 dose of 0.3 mL contains(blue cap) 10 micrograms of

Comirnaty Omicron XBB.1.5 raxtozinameran, a10 micrograms/dose dispersion Multidose COVID−19 mRNAfor injection (2.25 mL) vial 6 doses of 0.3 mL Vaccine (nucleoside(blue cap) modified, embeddedin lipidnanoparticles).

Raxtozinameran is a single-stranded, 5’-capped messenger RNA (mRNA) produced using a cell-freein vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of

SARS-CoV-2 (Omicron XBB.1.5).

For the full list of excipients, see section 6.1.

Dispersion for injection.

Comirnaty Omicron XBB.1.5 30 micrograms/dose dispersion for injection is a white to off-whitedispersion (pH: 6.9 - 7.9).

Comirnaty Omicron XBB.1.5 10 micrograms/dose dispersion is a clear to slightly opalescentdispersion (pH: 6.9 - 7.9).

Comirnaty Omicron XBB.1.5 dispersion for injection is indicated for active immunisation to prevent

COVID-19 caused by SARS-CoV-2 in individuals 5 years of age and older.

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

Comirnaty Omicron XBB.1.5 30 micrograms/dose dispersion for injection is administeredintramuscularly as a single dose of 0.3 mL for individuals 12 years of age and older regardless of prior

COVID-19 vaccination status (see sections 4.4 and 5.1).

For individuals who have previously been vaccinated with a COVID-19 vaccine, Comirnaty Omicron

XBB.1.5 should be administered at least 3 months after the most recent dose of a COVID-19 vaccine.

Children 5 to 11 years of age (i.e. 5 to less than 12 years of age)

Comirnaty Omicron XBB.1.5 10 micrograms/dose dispersion for injection is administeredintramuscularly as a single dose of 0.3 mL for children 5 to 11 years of age regardless of prior

COVID-19 vaccination status (see sections 4.4 and 5.1).

For individuals who have previously been vaccinated with a COVID-19 vaccine, Comirnaty Omicron

XBB.1.5 should be administered at least 3 months after the most recent dose of a COVID-19 vaccine.

Severely immunocompromised individuals

Additional doses may be administered to individuals who are severely immunocompromised inaccordance with national recommendations (see section 4.4).

There are paediatric formulations available for infants and children aged 6 months to 4 years. Fordetails, please refer to the Summary of Product Characteristics for other formulations.

The safety and efficacy of the vaccine in infants aged less than 6 months have not yet beenestablished.

No dose adjustment is required in elderly individuals 65 years of age and older.

Comirnaty Omicron XBB.1.5 dispersion for injection should be administered intramuscularly (seesection 6.6). Do not dilute prior to use.

The preferred site is 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 regarding thawing, handling and disposal of the vaccine, see section 6.6.

Single dose vials

Single dose vials of Comirnaty Omicron XBB.1.5 contain 1 dose of 0.3 mL of vaccine.

* Withdraw a single 0.3 mL dose of Comirnaty Omicron XBB.1.5.

* Discard vial and any excess volume.

* Do not pool excess vaccine from multiple vials.

Multidose vials

Multidose vials of Comirnaty Omicron XBB.1.5 contain 6 doses of 0.3 mL of vaccine. In order toextract 6 doses from a single vial, low dead-volume syringes and/or needles should be used. The lowdead-volume syringe and needle combination should have a dead-volume of no more than35 microlitres. If standard syringes and needles are used, there may not be sufficient volume to extracta sixth dose from a single vial. Irrespective of the type of syringe and needle:

* Each dose must contain 0.3 mL of vaccine.

* If the amount of vaccine remaining in the vial cannot provide a full dose of 0.3 mL, discard thevial and any excess volume.

* Do not pool excess vaccine from multiple vials.

Pre-filled syringes

* Each single dose pre-filled syringe of Comirnaty Omicron XBB.1.5 contains 1 dose of 0.3 mLof vaccine.

* Attach a needle appropriate for intramuscular injection and administer the entire volume.

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

In order to improve the traceability of biological medicinal products, the name and the batch numberof the administered product should be clearly recorded.

Events of anaphylaxis have been reported. Appropriate medical treatment and supervision shouldalways be readily available in case of an anaphylactic reaction following the administration of thevaccine.

Close observation for at least 15 minutes is recommended following vaccination. No further dose ofthe vaccine should be given to those who have experienced anaphylaxis after a prior dose of

Comirnaty.

There is an increased risk of myocarditis and pericarditis following vaccination with Comirnaty. Theseconditions can develop within just a few days after vaccination and have primarily occurred within14 days. They have been observed more often after the second vaccination, and more often in youngermales (see section 4.8). Available data indicate that most cases recover. Some cases required intensivecare support and fatal cases have been observed.

Healthcare professionals should be alert to the signs and symptoms of myocarditis and pericarditis.

Vaccinees (including parents or caregivers) should be instructed to seek immediate medical attentionif they develop symptoms indicative of myocarditis or pericarditis such as (acute and persisting) chestpain, shortness of breath, or palpitations following vaccination.

Healthcare professionals should consult guidance and/or specialists to diagnose and treat thiscondition.

Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress‐relatedreactions (e.g. dizziness, palpitations, increases in heart rate, alterations in blood pressure,paraesthesia, hypoaesthesia and sweating) may occur in association with the vaccination process itself.

Stress-related reactions are temporary and resolve on their own. Individuals should be advised to bringsymptoms to the attention of the vaccination provider for evaluation. It is important that precautionsare in place to avoid injury from fainting.

Vaccination should be postponed in individuals suffering from acute severe febrile illness or acuteinfection. The presence of a minor infection and/or low-grade fever should not delay vaccination.

As with other intramuscular injections, the vaccine should be given with caution in individualsreceiving anticoagulant therapy or those with thrombocytopenia or any coagulation disorder (such ashaemophilia) because bleeding or bruising may occur following an intramuscular administration inthese individuals.

Safety and immunogenicity have been assessed in a limited number of immunocompromisedindividuals, including those receiving immunosuppressant therapy (see sections 4.8 and 5.1). Theefficacy of Comirnaty Omicron XBB.1.5 may be lower in immunocompromised individuals.

The duration of protection afforded by the vaccine is unknown as it is still being determined byongoing clinical trials.

As with any vaccine, vaccination with Comirnaty Omicron XBB.1.5 may not protect all vaccinerecipients. Individuals may not be fully protected until 7 days after their vaccination.

Comirnaty Omicron XBB.1.5 30 micrograms/dose dispersion for injection may be administeredconcomitantly with seasonal influenza vaccine.

In individuals 18 years of age and older, Comirnaty Omicron XBB.1.5 may be administeredconcomitantly with a pneumococcal conjugate vaccine (PCV).

In individuals 18 years of age and older, Comirnaty Omicron XBB.1.5 may be administeredconcomitantly with an unadjuvanted recombinant protein respiratory syncytial virus (RSV) vaccine.

In individuals 65 years of age and older, Comirnaty Omicron XBB.1.5 may be administeredconcomitantly with an unadjuvanted recombinant protein RSV vaccine and a high dose influenzavaccine.

Different injectable vaccines should be administered at different injection sites.

Concomitant administration of Comirnaty Omicron XBB.1.5 10 micrograms/dose dispersion forinjection with other vaccines has not been studied.

No data are available yet regarding the use of Comirnaty Omicron XBB.1.5 during pregnancy.

However, there are limited clinical study data (less than 300 pregnancy outcomes) from the use of

Comirnaty in pregnant participants. A large amount of observational data from pregnant womenvaccinated with the initially approved Comirnaty vaccine during the second and third trimester havenot shown an increase in adverse pregnancy outcomes. While data on pregnancy outcomes followingvaccination during the first trimester are presently limited, no increased risk for miscarriage has beenseen. 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). Based on dataavailable with other vaccine variants, Comirnaty Omicron XBB.1.5 can be used during pregnancy.

No data are available yet regarding the use of Comirnaty Omicron XBB.1.5 during breast-feeding.

However, no effects on the breastfed newborn/infant are anticipated since the systemic exposure ofbreast-feeding woman to the vaccine is negligible. Observational data from women who werebreast-feeding after vaccination with the initially approved Comirnaty vaccine have not shown a riskfor adverse effects in breastfed newborns/infants. Comirnaty Omicron XBB.1.5 can be used duringbreast-feeding.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity(see section 5.3).

Comirnaty Omicron XBB.1.5 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 driveor use machines.

The safety of Comirnaty Omicron XBB.1.5 is inferred from safety data of the prior Comirnatyvaccines.

Initially approved Comirnaty vaccine

Children 5 to 11 years of age (i.e. 5 to less than 12 years of age) - after 2 doses

In Study 3, a total of 3 109 children 5 to 11 years of age received at least 1 dose of the initiallyapproved Comirnaty vaccine 10 mcg and a total of 1 538 children 5 to 11 years of age receivedplacebo. At the time of the analysis of Study 3 Phase 2/3 with data up to the cut-off date of 20 May2022, 2 206 (1 481 Comirnaty 10 mcg and 725 placebo) children have been followed for ≥ 4 monthsafter the second dose in the placebo-controlled blinded follow-up period. The safety evaluation in

Study 3 is ongoing.

The overall safety profile of Comirnaty in participants 5 to 11 years of age was similar to that seen inparticipants 16 years of age and older. The most frequent adverse reactions in children 5 to 11 years ofage that received 2 doses were injection site pain (> 80%), fatigue (> 50%), headache (> 30%),injection site redness and swelling (≥ 20%), myalgia, chills, and diarrhoea (> 10%).

Children 5 to 11 years of age (i.e. 5 to less than 12 years of age) - after booster dose

In a subset from Study 3, a total of 2 408 children 5 to 11 years of age received a booster dose of

Comirnaty 10 mcg at least 5 months (range of 5.3 to 19.4 months) after completing the primary series.

The analysis of the Study 3 Phase 2/3 subset is based on data up to the cut-off date of28 February 2023 (median follow-up time of 6.4 months).

The overall safety profile for the booster dose was similar to that seen after the primary course. Themost frequent adverse reactions in children 5 to 11 years of age after the booster dose were injectionsite pain (> 60%), fatigue (> 30%), headache (> 20%), myalgia, chills, injection site redness andswelling (> 10%).

In an analysis of long-term safety follow-up in Study 2, 2 260 adolescents (1 131 Comirnaty and1 129 placebo) were 12 to 15 years of age. Of these, 1 559 adolescents (786 Comirnaty and773 placebo) have been followed for ≥ 4 months after the second dose.

The overall safety profile of Comirnaty in adolescents 12 to 15 years of age was similar to that seen inparticipants 16 years of age and older. The most frequent adverse reactions in adolescents 12 to15 years of age that received 2 doses were injection site pain (> 90%), fatigue and headache (> 70%),myalgia and chills (> 40%), arthralgia and pyrexia (> 20%).

In Study 2, a total of 22 026 participants 16 years of age or older received at least 1 dose of theinitially approved Comirnaty vaccine and a total of 22 021 participants 16 years of age or olderreceived placebo (including 138 and 145 adolescents 16 and 17 years of age in the vaccine andplacebo groups, respectively). A total of 20 519 participants 16 years of age or older received 2 dosesof Comirnaty.

At the time of the analysis of Study 2 with a data cut-off of 13 March 2021 for the placebo-controlledblinded follow-up period up to the participants’ unblinding dates, a total of 25 651 (58.2%)participants (13 031 Comirnaty and 12 620 placebo) 16 years of age and older were followed up for≥ 4 months after the second dose. This included a total of 15 111 (7 704 Comirnaty and 7 407 placebo)participants 16 to 55 years of age and a total of 10 540 (5 327 Comirnaty and 5 213 placebo)participants 56 years of age and older.

The most frequent adverse reactions in participants 16 years of age and older that received 2 doseswere injection site pain (> 80%), fatigue (> 60%), headache (> 50%), myalgia (> 40%), chills(> 30%), arthralgia (> 20%), pyrexia and injection site swelling (> 10%) and were usually mild ormoderate in intensity and resolved within a few days after vaccination. A slightly lower frequency ofreactogenicity events was associated with greater age.

The safety profile in 545 participants 16 years of age and older receiving Comirnaty, that wereseropositive for SARS-CoV-2 at baseline, was similar to that seen in the general population.

Participants 12 years of age and older - after booster dose

A subset from Study 2 Phase 2/3 participants of 306 adults 18 to 55 years of age who completed theoriginal Comirnaty 2-dose course, received a booster dose of Comirnaty approximately 6 months(range of 4.8 to 8.0 months) after receiving Dose 2. Overall, participants who received a booster dose,had a median follow-up time of 8.3 months (range 1.1 to 8.5 months) and 301 participants had beenfollowed for ≥ 6 months after the booster dose to the cut-off date (22 November 2021).

The overall safety profile for the booster dose was similar to that seen after 2 doses. The most frequentadverse reactions in participants 18 to 55 years of age were injection site pain (> 80%),fatigue (> 60%), headache (> 40%), myalgia (> 30%), chills and arthralgia (> 20%).

In Study 4, a placebo-controlled booster study, participants 16 years of age and older recruited from

Study 2 received a booster dose of Comirnaty (5 081 participants), or placebo (5 044 participants) atleast 6 months after the second dose of Comirnaty. Overall, participants who received a booster dose,had a median follow-up time of 2.8 months (range 0.3 to 7.5 months) after the booster dose in theblinded placebo-controlled follow-up period to the cut-off date (8 February 2022). Of these,1 281 participants (895 Comirnaty and 386 placebo) have been followed for ≥ 4 months after thebooster dose of Comirnaty. No new adverse reactions of Comirnaty were identified.

A subset from Study 2 Phase 2/3 participants of 825 adolescents 12 to 15 years of age who completedthe original Comirnaty 2-dose course, received a booster dose of Comirnaty approximately11.2 months (range of 6.3 to 20.1 months) after receiving Dose 2. Overall, participants who received abooster dose, had a median follow-up time of 9.5 months (range 1.5 to 10.7 months) based on data upto the cut-off date (3 November 2022). No new adverse reactions of Comirnaty were identified.

Participants 12 years of age and older - after subsequent booster doses

The safety of a booster dose of Comirnaty in participants 12 years of age and older is inferred fromsafety data from studies of a booster dose of Comirnaty in participants 18 years of age and older.

A subset of 325 adults 18 to ≤ 55 years of age who had completed 3 doses of Comirnaty, received abooster (fourth dose) of Comirnaty 90 to 180 days after receiving Dose 3. Participants who received abooster (fourth dose) of Comirnaty had a median follow-up time of 1.4 months up to a data cut-offdate of 11 March 2022. The most frequent adverse reactions in these participants were injection sitepain (> 70%), fatigue (> 60%), headache (> 40%), myalgia and chills (> 20%), and arthralgia (> 10%).

In a subset from Study 4 (Phase 3), 305 adults > 55 years of age who had completed 3 doses of

Comirnaty, received a booster (fourth dose) of Comirnaty 5 to 12 months after receiving Dose 3.

Participants who received a booster (fourth dose) of Comirnaty had a median follow-up time of at least1.7 months up to a data cut-off date of 16 May 2022. The overall safety profile for the Comirnatybooster (fourth dose) was similar to that seen after the Comirnaty booster (third dose). The mostfrequent adverse reactions in participants > 55 years of age were injection site pain (> 60%),fatigue (> 40%), headache (> 20%), myalgia and chills (> 10%).

Booster dose following primary vaccination with another authorised COVID-19 vaccine

In 5 independent studies on the use of a Comirnaty booster dose in individuals who had completedprimary vaccination with another authorised COVID-19 vaccine (heterologous booster dose), no newsafety issues were identified.

Omicron-adapted Comirnaty

Children 5 to 11 years of age (i.e. 5 to less than 12 years of age) - after the booster (fourth dose)

In a subset from Study 6 (Phase 3), 113 participants 5 to 11 years of age who had completed 3 doses of

Comirnaty, received a booster (fourth dose) of Comirnaty Original/Omicron BA.4-5 (5/5 mcg) 2.6 to8.5 months after receiving Dose 3. Participants who received a booster (fourth dose) of Comirnaty

Original/Omicron BA.4-5 had a median follow-up time of 6.3 months.

The overall safety profile for the Comirnaty Original/Omicron BA.4-5 booster (fourth dose) wassimilar to that seen after 3 doses. The most frequent adverse reactions in participants 5 to 11 years ofage were injection site pain (> 60%), fatigue (> 40%), headache (> 20%), and muscle pain (> 10%).

Participants 12 years of age and older - after a booster dose of Comirnaty Original/Omicron BA.4-5(fourth dose)

In a subset from Study 5 (Phase 2/3), 107 participants 12 to 17 years of age, 313 participants 18 to55 years of age and 306 participants 56 years of age and older who had completed 3 doses of

Comirnaty, received a booster (fourth dose) of Comirnaty Original/Omicron BA.4-5 (15/15 mcg) 5.4to 16.9 months after receiving Dose 3. Participants who received a booster (fourth dose) of Comirnaty

Original/Omicron BA.4-5 had a median follow-up time of at least 1.5 months.

The overall safety profile for the Comirnaty Original/Omicron BA.4-5 booster (fourth dose) wassimilar to that seen after 3 doses. The most frequent adverse reactions in participants 12 years of ageand older were injection site pain (> 60%), fatigue (> 50%), headache (> 40%), muscle pain (> 20%),chills (> 10%), and joint pain (> 10%).

Tabulated list of adverse reactions from clinical studies of Comirnaty and Comirnaty

Original/Omicron BA.4-5 and post-authorisation experience of Comirnaty in individuals 5 years ofage and older

Adverse reactions observed during clinical studies and post-authorisation experience are listed belowaccording 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).

Table 2. Adverse reactions from Comirnaty and Comirnaty Original/Omicron BA.4-5 clinicaltrials and Comirnaty post-authorisation experience in individuals 5 years of age andolder

System Organ Class Frequency Adverse reactions

Blood and lymphatic system Common Lymphadenopathyadisorders

Immune system disorders Uncommon Hypersensitivity reactions (e.g. rash,pruritus, urticariab, angioedemab)

Not known Anaphylaxis

Metabolism and nutrition disorders Uncommon Decreased appetite

Psychiatric disorders Uncommon Insomnia

Nervous system disorders Very common Headache

Uncommon Dizzinessd; lethargy

Rare Acute peripheral facial paralysisc

Not known Paraesthesiad; hypoaesthesiad

Cardiac disorders Very rare Myocarditisd; pericarditisd

Gastrointestinal disorders Very common Diarrhoead

Common Nausea; vomitingd,j

Skin and subcutaneous tissue Uncommon Hyperhidrosis; night sweatsdisorder Not known Erythema multiformed

Musculoskeletal and connective Very common Arthralgia; myalgiatissue disorders Uncommon Pain in extremitye

Reproductive system and breast Not known Heavy menstrual bleedingidisorders

General disorders and Very common Injection site pain; fatigue; chills;administration site conditions pyrexiaf; injection site swelling

Common Injection site rednessh

Uncommon Asthenia; malaise; injection site pruritus

Not known Extensive swelling of vaccinated limbd;facial swellingg

a. In participants 5 years of age and older, a higher frequency of lymphadenopathy was reported after a booster(≤ 2.8%) dose than after primary (≤ 0.9%) doses of the vaccine.

b. The frequency category for urticaria and angioedema was rare.

c. Through the clinical trial safety follow-up period to 14 November 2020, acute peripheral facial paralysis (orpalsy) was reported by four participants in the COVID-19 mRNA Vaccine group. Onset was Day 37 after

Dose 1 (participant did not receive Dose 2) and Days 3, 9, and 48 after Dose 2. No cases of acute peripheralfacial paralysis (or palsy) were reported in the placebo group.

d. Adverse reaction determined post-authorisation.

e. Refers to vaccinated arm.

f. A higher frequency of pyrexia was observed after the second dose compared to the first dose.g. Facial swelling in vaccine recipients with a history of injection of dermatological fillers has been reported inthe post-marketing phase.

h. Injection site redness occurred at a higher frequency (very common) in children 5 to 11 years of age and inimmunocompromised participants 5 years of age and older.

i. Most cases appeared to be non-serious and temporary in nature.j. The frequency category for vomiting was very common in pregnant women 18 years of age and older and inimmunocompromised participants 5 to 18 years of age.

Infants born to pregnant participants - after 2 doses of Comirnaty

Study C4591015 (Study 9), a Phase 2/3, placebo-controlled study, evaluated a total of 346 pregnantparticipants who received Comirnaty (n = 173) or placebo (n = 173). Infants (Comirnaty n = 167 orplacebo n = 168) were evaluated up to 6 months. No safety concerns were identified that wereattributable to maternal vaccination with Comirnaty.

Immunocompromised participants (adults and children)

In study C4591024 (Study 10), a total of 124 immunocompromised participants 2 years of age andolder received Comirnaty (see section 5.1).

Safety with concomitant vaccine administration

Concomitant administration with seasonal influenza vaccine

In Study 8, a Phase 3 study, participants 18 through 64 years of age who received Comirnatycoadministered with seasonal inactivated influenza vaccine (SIIV), quadrivalent followed 1 monthlater by placebo, were compared to participants who received an inactivated influenza vaccine withplacebo followed 1 month later by Comirnaty alone (n = 553 to 564 participants in each group).

Concomitant administration with pneumococcal conjugate vaccine

In Study 11 (B7471026), a Phase 3 study, participants 65 years of age and older who received abooster dose of Comirnaty coadministered with 20-valent pneumococcal conjugate vaccine (20vPNC)(n = 187) were compared to participants who received Comirnaty alone (n = 185).

Concomitant administration with an unadjuvanted recombinant protein RSV vaccine or with anunadjuvanted recombinant protein RSV vaccine and a high dose influenza vaccine

In Study 12 (C5481001), a Phase 1/2 study, participants 65 years of age and older who received

Comirnaty Original/Omicron BA.4-5 and RSV vaccine coadministered in one arm plus high dosequadrivalent influenza vaccine (QIV) (n = 158) or placebo (n = 157) in the opposite arm werecompared to participants who received the individual vaccines given with placebo.

The increased risk of myocarditis after vaccination with Comirnaty is highest in younger males (seesection 4.4).

Two large European pharmacoepidemiological studies have estimated the excess risk in youngermales following the second dose of Comirnaty. One study showed that in a period of 7 days after thesecond dose there were about 0.265 (95% CI: 0.255 - 0.275) extra cases of myocarditis in 12-29 yearold males per 10 000 compared to unexposed persons. In another study, in a period of 28 days after thesecond dose there were 0.56 (95% CI: 0.37 - 0.74) extra cases of myocarditis in 16-24 year old malesper 10 000 compared to unexposed persons.

Limited data indicate that the risk of myocarditis and pericarditis after vaccination with Comirnaty inchildren aged 5 to 11 years seems lower than in ages 12 to 17 years.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

There have been reports of higher than recommended doses of Comirnaty in clinical trials andpost−authorisation experience. In general, adverse events reported with overdoses have been similar tothe known adverse reaction profile of Comirnaty.

In the event of overdose, monitoring of vital functions and possible symptomatic treatment isrecommended.

Pharmacotherapeutic group: vaccines, viral vaccines, ATC code: J07BN01

The nucleoside modified messenger RNA in Comirnaty is formulated in lipid nanoparticles, whichenable delivery of the non-replicating RNA into host cells to direct transient expression of the

SARS-CoV-2 S antigen. The mRNA codes for membrane-anchored, full-length S with two pointmutations within the central helix. Mutation of these two amino acids to proline locks S in anantigenically preferred prefusion conformation. The vaccine elicits both neutralising antibody andcellular immune responses to the spike (S) antigen, which may contribute to protection against

COVID-19.

Omicron-adapted Comirnaty

Immunogenicity in children 5 to 11 years of age (i.e. 5 to less than 12 years of age) - after the booster(fourth dose)

In an analysis of a subset from Study 6, 103 participants 5 to 11 years of age who had previouslyreceived a 2-dose primary series and booster dose with Comirnaty received a booster (fourth dose) of

Comirnaty Original/Omicron BA.4-5. Results include immunogenicity data from a comparator subsetof participants 5 to 11 years of age in Study 3 who received 3 doses of Comirnaty. In participants 5 to11 years of age who received a fourth dose of Comirnaty Original/Omicron BA.4-5 and participants5 to 11 years of age who received a third dose of Comirnaty, 57.3% and 58.4% were positive for

SARS-CoV-2 at baseline, respectively.

The immune response 1 month after a booster dose (fourth dose), Comirnaty Original/Omicron

BA.4-5 elicited generally similar Omicron BA.4/BA.5-specific neutralising titres compared with thetitres in the comparator group who received 3 doses of Comirnaty. Comirnaty Original/Omicron

BA.4-5 also elicited similar reference strain-specific titres compared with the titres in the comparatorgroup.

The vaccine immunogenicity results after a booster dose in participants 5 to 11 years of age arepresented in Table 3.

Table 3. Study 6 - Geometric mean ratio and Geometric mean titres - participants with orwithout evidence of infection - 5 to 11 years of age - evaluable immunogenicitypopulation

Vaccine Group (as Assigned/Randomised)

Study 6

Comirnaty(Original/Omicron Study 3 Study 6

BA.4/BA.5) Comirnaty Comirnaty10 mcg 10 mcg (Original/Omicron

Dose 4 and Dose 3 and BA.4/BA.5)/Comirnaty

SARS-CoV-2 Sampling 1 Month After Dose 4 1 Month After Dose 3 10 mcgneutralisation time GMTc GMTc GMRdassay pointa nb (95% CIc) nb (95% CIc) (95% CId)

Omicron Pre- 488.3 248.3

BA.4-5 - NT50 vaccination 102 (361.9, 658.8) 112 (187.2, 329.5) -(titre)e 2 189.9 1 393.6 1.121 month 102 (1 742.8, 2 751.7) 113 (1 175.8, 1 651.7) (0.92, 1.37)

Reference Pre- 2 904.0 1 323.1 -strain - NT50 vaccination 102 (2 372.6, 3 554.5) 113 (1 055.7, 1 658.2)(titre)e 8 245.9 7 235.11 month 102 (7 108.9, 9 564.9) 113 (6 331.5, 8 267.8) -

Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titre;

LLOQ = lower limit of quantitation; LS = least square; N-binding = SARS-CoV-2 nucleoprotein-binding;

NT50 = 50% neutralising titre; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

a. Protocol-specified timing for blood sample collection.

b. n = Number of participants with valid and determinate assay results for the specified assay at the givensampling time point.

c. GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titres and thecorresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to0.5 × LLOQ.

d. GMRs and 2-sided CIs were calculated by exponentiating the difference of LS Means for the assay and thecorresponding CIs based on analysis of log-transformed assay results using a linear regression model withbaseline log-transformed neutralising titres, postbaseline infection status, and vaccine group as covariates.

e. SARS-CoV-2 NT50 were determined using a validated 384-well assay platform (original strain[USA-WA1/2020, isolated in January 2020] and Omicron B.1.1.529 subvariant BA.4/BA.5).

Immunogenicity in participants 12 years of age and older - after the booster (fourth dose)

In an analysis of a subset from Study 5, 105 participants 12 to 17 years of age, 297 participants 18 to55 years of age, and 286 participants 56 years of age and older who had previously received a 2-doseprimary series and booster dose with Comirnaty received a booster (fourth dose) of Comirnaty

Original/Omicron BA.4-5. In participants 12 to 17 years of age, 18 to 55 years of age, and 56 years ofage and older, 75.2%, 71.7% and 61.5% were positive for SARS-CoV-2 at baseline, respectively.

Analyses of 50% neutralising antibody titres (NT50) against Omicron BA.4-5 and against referencestrain among participants 56 years of age and older who received a booster (fourth dose) of Comirnaty

Original/Omicron BA.4-5 in Study 5 compared to a subset of participants from Study 4 who receiveda booster (fourth dose) of Comirnaty demonstrated superiority of Comirnaty Original/Omicron BA.4-5to Comirnaty based on geometric mean ratio (GMR) and noninferiority based on difference inseroresponse rates with respect to anti-Omicron BA.4-5 response, and noninferiority of anti-referencestrain immune response based on GMR (Table 4).

Analyses of NT50 against Omicron BA.4/BA.5 among participants 18 to 55 years of age compared toparticipants 56 years of age and older who received a booster (fourth dose) of Comirnaty

Original/Omicron BA.4-5 in Study 5 demonstrated noninferiority of anti-Omicron BA.4-5 responseamong participants 18 to 55 years of age compared to participants 56 years of age and older for both

GMR and difference in seroresponse rates (Table 4).

The study also assessed the level of NT50 of the anti-Omicron BA.4-5 SARS-CoV-2 and referencestrains pre-vaccination and 1 month after vaccination in participants who received a booster (fourthdose) (Table 5).

Table 4. SARS-CoV-2 GMTs (NT50) and difference in percentages of participants withseroresponse at 1 month after vaccination course - Comirnaty Original/Omicron

BA.4-5 from Study 5 and Comirnaty from subset of Study 4 - participants with orwithout evidence of SARS-CoV-2 infection - evaluable immunogenicity population

SARS-CoV-2 GMTs (NT50) at 1 month after vaccination course

Study 5

Comirnaty Subset of Study 4 Age group Vaccine group

Original/Omicron BA.4-5 Comirnaty comparison comparison

Comirnaty

Original/ ≥ 56 years of age

Omicron BA.4-5 Comirnaty18 to 55 years of Original/18 to 55 years of 56 years of age 56 years of age age/≥ 56 years of Omicron BA.4-5age and older and older age /Comirnaty

SARS-CoV-2 GMTbneutralisation GMTc (95% GMTb GMRc GMRcassay na (95% CIc) na CIb) na (95% CIb) (95% CIc) (95% CIc)

Omicron BA.4-5 - 4 455.9 4 158.1 938.9

NT50 (titre)d 297 (3 851.7, 284 (3 554.8, 282 (802.3, 0.98 2.915 154.8) 4 863.8) 1 098.8) (0.83, 1.16)e (2.45, 3.44)f

Reference Strain - 16 250.1 10 415.5

- - 286 (14 499.2, 289 (9 366.7, - 1.38

NT50 (titre)d g18 212.4) 11 581.8) (1.22, 1.56)

Difference in percentages of participants with seroresponse at 1 month after vaccination course

Comirnaty Subset of Study 4 Age group Vaccine group

Original/Omicron BA.4-5 Comirnaty comparison comparison≥ 56 years of age

Comirnaty Comirnaty18 to 55 years of 56 years of age 56 years of age Original/Omicroage and older and older n BA.4-5 Original/18 to 55 years of Omicron BA.4-5age/≥ 56 /Comirnaty

SARS-CoV-2 ii n (%) i kneutralisation Nh n (%) h h n (%) Difference Differencek(95% CIk (95%assay ) N N

CIk) (95% CIj) (95% CIl) (95% CIl)

Omicron BA.4-5 - 294 180 (61.2) 188 (66.7) 127 (46.5) -3.03 26.77

NT50 (titre)d (55.4, 282 (60.8, 273 (40.5, 52.6) (-9.68, 3.63)m (19.59, 33.95)n66.8) 72.1)

Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titre;

LLOQ = lower limit of quantitation; LS = least square; NT50 = 50% neutralising titre; SARS-CoV-2 = severeacute respiratory syndrome coronavirus 2.

Note: Seroresponse is defined as achieving a ≥ 4-fold rise from baseline. If the baseline measurement is belowthe LLOQ, a post-vaccination assay result ≥ 4 × LLOQ is considered a seroresponse.

a. n = Number of participants with valid and determinate assay results for the specified assay at the givensampling time point.

b. GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titres and thecorresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to0.5 × LLOQ.

c. GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of LS means andcorresponding CIs based on analysis of logarithmically transformed neutralising titres using a linearregression model with terms of baseline neutralising titre (log scale) and vaccine group or age group.

d. SARS-CoV-2 NT50 were determined using a validated 384-well assay platform (original strain[USA-WA1/2020, isolated in January 2020] and Omicron B.1.1.529 subvariant BA.4/BA.5).

e. Noninferiority is declared if the lower bound of the 2-sided 95% CI for the GMR is greater than 0.67.

f. Superiority is declared if the lower bound of the 2-sided 95% CI for the GMR is greater than 1.g. Noninferiority is declared if the lower bound of the 2-sided 95% CI for the GMR is greater than 0.67 and thepoint estimate of the GMR is ≥ 0.8.

h. N = Number of participants with valid and determinate assay results for the specified assay at both the pre-vaccination time point and the given sampling time point. This value is the denominator for the percentagecalculation.

i. n = Number of participants with seroresponse for the given assay at the given sampling time point.j. Exact 2-sided CI, based on the Clopper and Pearson method.k. Difference in proportions, expressed as a percentage.l. 2-sided CI based on the Miettinen and Nurminen method stratified by baseline neutralising titre category(< median, ≥ median) for the difference in proportions. The median of baseline neutralising titres wascalculated based on the pooled data in 2 comparator groups.

m. Noninferiority is declared if the lower bound of the 2-sided 95% CI for the difference in percentages ofparticipants with seroresponse is > -10%.

n. Noninferiority is declared if the lower bound of the 2-sided 95% CI for the difference in percentages ofparticipants with seroresponse is > -5%.

Table 5. Geometric mean titres - Comirnaty Original/Omicron BA.4-5 subsets of Study 5 -prior to and 1 month after booster (fourth dose) - participants 12 years of age andolder - with or without evidence of infection - evaluable immunogenicity population

Comirnaty

Original/Omicron BA.4-512 to 17 years of age 18 to 55 years of age 56 years of age and older

SARS-CoV-2 Samplingneutralisation time GMTc GMTc GMTcassay pointa nb (95% CIc) nb (95% CIc) nb (95% CIc)

Pre- 1 105.8 569.6 458.2

Omicron BA.4- vaccination 104 (835.1, 1 464.3) 294 (471.4, 688.2) 284 (365.2, 574.8)5 - NT50 (titre)d 8 212.8(6 807.3, 4 455.9 4 158.11 month 105 9 908.7) 297 (3 851.7, 5 154.8) 284 (3 554.8, 4 863.8)6 863.3

Reference Pre- (5 587.8, 4 017.3 3 690.6

Strain - NT50 vaccination 105 8 430.1) 296 (3 430.7, 4 704.1) 284 (3 082.2, 4 419.0)(titre)d 23 641.3(20 473.1, 16 323.3 16 250.11 month 105 27 299.8) 296 (14 686.5, 18 142.6) 286 (14 499.2, 18 212.4)

Abbreviations: CI = confidence interval; GMT = geometric mean titre; LLOQ = lower limit of quantitation;

NT50 = 50% neutralising titre; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

a. Protocol-specified timing for blood sample collection.

b. n = Number of participants with valid and determinate assay results for the specified assay at the givensampling time point.

c. GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titres and thecorresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to0.5 × LLOQ.

d. SARS-CoV-2 NT50 were determined using a validated 384-well assay platform (original strain[USA-WA1/2020, isolated in January 2020] and Omicron B.1.1.529 subvariant BA.4-5).

Initially approved Comirnaty vaccine

Study 2 is a multicentre, multinational, Phase 1/2/3 randomised, placebo-controlled, observer-blinddose-finding, vaccine candidate selection and efficacy study in participants 12 years of age and older.

Randomisation was stratified by age: 12 to 15 years of age, 16 to 55 years of age, or 56 years of ageand older, with a minimum of 40% of participants in the ≥ 56-year stratum. The study excludedparticipants who were immunocompromised and those who had previous clinical or microbiologicaldiagnosis of COVID-19. Participants with pre-existing stable disease, defined as disease not requiringsignificant change in therapy or hospitalisation for worsening disease during the 6 weeks beforeenrolment, were included as were participants with known stable infection with humanimmunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV).

In the Phase 2/3 portion of Study 2, based on data accrued through 14 November 2020, approximately44 000 participants were randomised equally and were to receive 2 doses of the initially approved

COVID-19 mRNA Vaccine or placebo. The efficacy analyses included participants that received theirsecond vaccination within 19 to 42 days after their first vaccination. The majority (93.1%) of vaccinerecipients received the second dose 19 days to 23 days after Dose 1. Participants are planned to befollowed for up to 24 months after Dose 2, for assessments of safety and efficacy against COVID-19.

In the clinical study, participants were required to observe a minimum interval of 14 days before andafter administration of an influenza vaccine in order to receive either placebo or COVID-19 mRNA

Vaccine. In the clinical study, participants were required to observe a minimum interval of 60 daysbefore or after receipt of blood/plasma products or immunoglobulins within through conclusion of thestudy in order to receive either placebo or COVID-19 mRNA Vaccine.

The population for the analysis of the primary efficacy endpoint included 36 621 participants 12 yearsof age and older (18 242 in the COVID-19 mRNA Vaccine group and 18 379 in the placebo group)who did not have evidence of prior infection with SARS-CoV-2 through 7 days after the second dose.

In addition, 134 participants were between the ages of 16 to 17 years of age (66 in the COVID-19mRNA Vaccine group and 68 in the placebo group) and 1 616 participants 75 years of age and older(804 in the COVID-19 mRNA Vaccine group and 812 in the placebo group).

At the time of the primary efficacy analysis, participants had been followed for symptomatic

COVID-19 for in total 2 214 person-years for the COVID-19 mRNA Vaccine and in total2 222 person-years in the placebo group.

There were no meaningful clinical differences in overall vaccine efficacy in participants who were atrisk of severe COVID-19 including those with 1 or more comorbidities that increase the risk of severe

COVID-19 (e.g. asthma, body mass index (BMI) ≥ 30 kg/m2, chronic pulmonary disease, diabetesmellitus, hypertension).

The vaccine efficacy information is presented in Table 6.

Table 6. Vaccine efficacy - First COVID-19 occurrence from 7 days after Dose 2, by agesubgroup - participants without evidence of infection prior to 7 days after

Dose 2 - evaluable efficacy (7 days) population

First COVID-19 occurrence from 7 days after Dose 2 in participants without evidence of prior

SARS-CoV-2 infection*

COVID-19 mRNA

Vaccine Placebo

Na = 18 198 Na = 18 325

Cases Casesn1b n1b Vaccine efficacy %

Subgroup Surveillance timec (n2d) Surveillance timec (n2d) (95% CI)e8 162 95.0

All participants 2.214 (17 411) 2.222 (17 511) (90.0, 97.9)7 143 95.116 to 64 years 1.706 (13 549) 1.710 (13 618) (89.6, 98.1)1 19 94.765 years and older 0.508 (3 848) 0.511 (3 880) (66.7, 99.9)1 14 92.965 to 74 years 0.406 (3 074) 0.406 (3 095) (53.1, 99.8)75 years and 0 5 100.0older 0.102 (774) 0.106 (785) (-13.1, 100.0)

Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and atleast 1 symptom consistent with COVID-19 [*Case definition: (at least 1 of) fever, new or increased cough, newor increased shortness of breath, chills, new or increased muscle pain, new loss of taste or smell, sore throat,diarrhoea or vomiting.]

* Participants who had no serological or virological evidence (prior to 7 days after receipt of the last dose) ofpast SARS-CoV-2 infection (i.e. N-binding antibody [serum] negative at Visit 1 and SARS-CoV-2 notdetected by nucleic acid amplification tests (NAAT) [nasal swab] at Visits 1 and 2), and had negative NAAT(nasal swab) at any unscheduled visit prior to 7 days after Dose 2 were included in the analysis.

a. N = Number of participants in the specified group.

b. n1 = Number of participants meeting the endpoint definition.

c. Total surveillance time in 1 000 person-years for the given endpoint across all participants within each groupat risk for the endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of thesurveillance period.

d. n2 = Number of participants at risk for the endpoint.

e. Two-sided confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson methodadjusted to the surveillance time. CI not adjusted for multiplicity.

Dose 2 compared to placebo was 94.6% (95% confidence interval of 89.6% to 97.6%) in participants16 years of age and older with or without evidence of prior infection with SARS-CoV-2.

Additionally, subgroup analyses of the primary efficacy endpoint showed similar efficacy pointestimates across genders, ethnic groups, and participants with medical comorbidities associated withhigh risk of severe COVID-19.

Updated efficacy analyses were performed with additional confirmed COVID-19 cases accrued duringblinded placebo-controlled follow-up, representing up to 6 months after Dose 2 in the efficacypopulation.

The updated vaccine efficacy information is presented in Table 7.

Table 7. Vaccine efficacy - First COVID-19 occurrence from 7 days after Dose 2, by agesubgroup - participants without evidence of prior SARS-CoV-2 infection* prior to7 days after Dose 2 - evaluable efficacy (7 days) population during theplacebo-controlled follow-up period

COVID-19 mRNA

Vaccine Placebo

Na=20 998 Na=21 096

Cases Casesn1b n1b

Surveillance timec Surveillance timec Vaccine efficacy %

Subgroup (n2d) (n2d) (95% CIe)77 850 91.3

All participantsf 6.247 (20 712) 6.003 (20 713) (89.0, 93.2)70 710 90.616 to 64 years 4.859 (15 519) 4.654 (15 515) (87.9, 92.7)7 124 94.565 years and older 1.233 (4 192) 1.202 (4 226) (88.3, 97.8)6 98 94.165 to 74 years 0.994 (3 350) 0.966 (3 379) (86.6, 97.9)1 26 96.275 years and older 0.239 (842) 0.237 (847) (76.9, 99.9)

Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and atleast 1 symptom consistent with COVID-19 (symptoms included: fever; new or increased cough; new orincreased shortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat;diarrhoea; vomiting).

* Participants who had no evidence of past SARS-CoV-2 infection (i.e. N-binding antibody [serum] negative at

Visit 1 and SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT(nasal swab) at any unscheduled visit prior to 7 days after Dose 2 were included in the analysis.

a. N = Number of participants in the specified group.

b. n1 = Number of participants meeting the endpoint definition.

c. Total surveillance time in 1 000 person-years for the given endpoint across all participants within each groupat risk for the endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of thesurveillance period.

d. n2 = Number of participants at risk for the endpoint.

e. Two-sided 95% confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearsonmethod adjusted to the surveillance time.

f. Included confirmed cases in participants 12 to 15 years of age: 0 in the COVID-19 mRNA Vaccine group; 16in the placebo group.

In the updated efficacy analysis, efficacy of COVID-19 mRNA Vaccine in preventing first COVID-19occurrence from 7 days after Dose 2 compared to placebo was 91.1% (95% CI of 88.8% to 93.0%)during the period when Wuhan/wild-type and Alpha variants were the predominant circulating strainsin participants in the evaluable efficacy population with or without evidence of prior infection with

SARS-CoV-2.

Additionally, the updated efficacy analyses by subgroup showed similar efficacy point estimatesacross sexes, ethnic groups, geography and participants with medical comorbidities and obesityassociated with high risk of severe COVID-19.

Updated efficacy analyses of secondary efficacy endpoints supported benefit of the COVID-19 mRNA

Vaccine in preventing severe COVID‑19.

As of 13 March 2021, vaccine efficacy against severe COVID-19 is presented only for participantswith or without prior SARS-CoV-2 infection (Table 8) as the COVID-19 case counts in participantswithout prior SARS-CoV-2 infection were the same as those in participants with or without prior

SARS-CoV-2 infection in both the COVID-19 mRNA Vaccine and placebo groups.

Table 8. Vaccine efficacy - First severe COVID-19 occurrence in participants with or withoutprior SARS-CoV-2 infection based on the Food and Drug Administration (FDA)*after Dose 1 or from 7 days after Dose 2 in the placebo-controlled follow-up

COVID-19 mRNA

Vaccine Placebo

Cases Casesn1a n1a

Surveillance time Surveillance time Vaccine efficacy %(n2b) (n2b) (95% CIc)1 30 96.7

After Dose 1d 8.439e (22 505) 8.288e (22 435) (80.3, 99.9)1 21 95.37 days after Dose 2f 6.522g (21 649) 6.404g (21 730) (70.9, 99.9)

Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and atleast 1 symptom consistent with COVID-19 (symptoms included: fever; new or increased cough; new orincreased shortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat;diarrhoea; vomiting).

* Severe illness from COVID-19 as defined by FDA is confirmed COVID-19 and presence of at least 1 of thefollowing:

* Clinical signs at rest indicative of severe systemic illness (respiratory rate ≥ 30 breaths per minute, heartrate ≥ 125 beats per minute, saturation of oxygen ≤ 93% on room air at sea level, or ratio of arterialoxygen partial pressure to fractional inspired oxygen < 300 mm Hg);

* Respiratory failure [defined as needing high-flow oxygen, noninvasive ventilation, mechanicalventilation or extracorporeal membrane oxygenation (ECMO)];

* Evidence of shock (systolic blood pressure < 90 mm Hg, diastolic blood pressure < 60 mm Hg, orrequiring vasopressors);

* Significant acute renal, hepatic, or neurologic dysfunction;

* Admission to an Intensive Care Unit;

* Death.

a. n1 = Number of participants meeting the endpoint definition.

b. n2 = Number of participants at risk for the endpoint.

c. Two-side confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson methodadjusted to the surveillance time.

d. Efficacy assessed based on the Dose 1 all available efficacy (modified intention-to-treat) population thatincluded all randomised participants who received at least 1 dose of study intervention.

e. Total surveillance time in 1 000 person-years for the given endpoint across all participants within each groupat risk for the endpoint. Time period for COVID-19 case accrual is from Dose 1 to the end of the surveillanceperiod.

f. Efficacy assessed based on the evaluable efficacy (7 Days) population that included all eligible randomisedparticipants who receive all dose(s) of study intervention as randomised within the predefined window, haveno other important protocol deviations as determined by the clinician.

g. Total surveillance time in 1 000 person-years for the given endpoint across all participants within each groupat risk for the endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of thesurveillance period.

In an initial analysis of Study 2 in adolescents 12 to 15 years of age (representing a median follow-upduration of > 2 months after Dose 2) without evidence of prior infection, there were no cases in1 005 participants who received the vaccine and 16 cases out of 978 who received placebo. The pointestimate for efficacy is 100% (95% confidence interval 75.3, 100.0). In participants with or withoutevidence of prior infection there were 0 cases in the 1 119 who received vaccine and 18 cases in1 110 participants who received placebo. This also indicates the point estimate for efficacy is 100%(95% confidence interval 78.1, 100.0).

Updated efficacy analyses were performed with additional confirmed COVID-19 cases accrued duringblinded placebo-controlled follow-up, representing up to 6 months after Dose 2 in the efficacypopulation.

In the updated efficacy analysis of Study 2 in adolescents 12 to 15 years of age without evidence ofprior infection, there were no cases in 1 057 participants who received the vaccine and 28 cases out of1 030 who received placebo. The point estimate for efficacy is 100% (95% confidence interval 86.8,100.0) during the period when Alpha variant was the predominant circulating strain. In participantswith or without evidence of prior infection there were 0 cases in the 1 119 who received vaccine and30 cases in 1 109 participants who received placebo. This also indicates the point estimate for efficacyis 100% (95% confidence interval 87.5, 100.0).

In Study 2, an analysis of SARS-CoV-2 neutralising titres 1 month after Dose 2 was conducted in arandomly selected subset of participants who had no serological or virological evidence of past

SARS-CoV-2 infection up to 1 month after Dose 2, comparing the response in adolescents 12 to15 years of age (n = 190) to participants 16 to 25 years of age (n = 170).

The ratio of the geometric mean titres (GMT) in the 12 to 15 years of age group to the 16 to 25 yearsof age group was 1.76, with a 2-sided 95% CI of 1.47 to 2.10. Therefore, the 1.5-fold noninferioritycriterion was met as the lower bound of the 2-sided 95% CI for the geometric mean ratio [GMR] was> 0.67.

Efficacy and immunogenicity in children 5 to 11 years of age (i.e. 5 to less than 12 years of age) -after 2 doses

Study 3 is a Phase 1/2/3 study comprised of an open-label vaccine dose-finding portion (Phase 1) anda multicentre, multinational, randomised, saline placebo-controlled, observer-blind efficacy portion(Phase 2/3) that has enrolled participants 5 to 11 years of age. The majority (94.4%) of randomisedvaccine recipients received the second dose 19 days to 23 days after Dose 1.

Initial descriptive vaccine efficacy results in children 5 to 11 years of age without evidence of prior

SARS-CoV-2 infection are presented in Table 9. No cases of COVID-19 were observed in either thevaccine group or the placebo group in participants with evidence of prior SARS-CoV-2 infection.

Table 9. Vaccine efficacy - First COVID-19 occurrence from 7 days after Dose 2: Withoutevidence of infection prior to 7 days after Dose 2 - Phase 2/3 - Children 5 to 11 yearsof age evaluable efficacy population

First COVID-19 occurrence from 7 days after Dose 2 in children 5 to 11 years of age withoutevidence of prior SARS-CoV-2 infection*

COVID-19 mRNA

Vaccine10 mcg/dose Placebo

Na=1 305 Na=663

Cases Casesn1b n1b Vaccine efficacy

Surveillance timec Surveillance timec %(n2d) (n2d) (95% CI)

Children 5 to 11 years 3 16 90.7of age 0.322 (1 273) 0.159 (637) (67.7, 98.3)

Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and atleast 1 symptom consistent with COVID-19 (symptoms included: fever; new or increased cough; new or increasedshortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat; diarrhoea;vomiting).

* Participants who had no evidence of past SARS-CoV-2 infection (i.e. N-binding antibody [serum] negative at

Visit 1 and SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT(nasal swab) at any unscheduled visit prior to 7 days after Dose 2 were included in the analysis.

a. N = Number of participants in the specified group.

b. n1 = Number of participants meeting the endpoint definition.

c. Total surveillance time in 1 000 person-years for the given endpoint across all participants within each groupat risk for the endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of thesurveillance period.

d. n2 = Number of participants at risk for the endpoint.

Pre-specified hypothesis-driven efficacy analysis was performed with additional confirmed

COVID-19 cases accrued during blinded placebo-controlled follow-up, representing up to 6 monthsafter Dose 2 in the efficacy population.

In the efficacy analysis of Study 3 in children 5 to 11 years of age without evidence of prior infection,there were 10 cases in 2 703 participants who received the vaccine and 42 cases out of 1 348 whoreceived placebo. The point estimate for efficacy is 88.2% (95% confidence interval 76.2, 94.7) duringthe period when Delta variant was the predominant circulating strain. In participants with or withoutevidence of prior infection there were 12 cases in the 3 018 who received vaccine and 42 cases in1 511 participants who received placebo. The point estimate for efficacy is 85.7% (95% confidenceinterval 72.4, 93.2).

In Study 3, an analysis of SARS-CoV-2 50% neutralising titres (NT50) 1 month after Dose 2 in arandomly selected subset of participants demonstrated effectiveness by immunobridging of immuneresponses comparing children 5 to 11 years of age (i.e. 5 to less than 12 years of age) in the Phase 2/3part of Study 3 to participants 16 to 25 years of age in the Phase 2/3 part of Study 2 who had noserological or virological evidence of past SARS-CoV-2 infection up to 1 month after Dose 2, meetingthe pre-specified immunobridging criteria for both the geometric mean ratio (GMR) and theseroresponse difference with seroresponse defined as achieving at least 4-fold rise in SARS-CoV-2

NT50 from baseline (before Dose 1).

The GMR of the SARS-CoV-2 NT50 1 month after Dose 2 in children 5 to 11 years of age (i.e. 5 toless than 12 years of age) to that of young adults 16 to 25 years of age was 1.04 (2-sided 95% CI: 0.93,1.18). Among participants without prior evidence of SARS-CoV-2 infection up to 1 month after

Dose 2, 99.2% of children 5 to 11 years of age and 99.2% of participants 16 to 25 years of age had aseroresponse at 1 month after Dose 2. The difference in proportions of participants who hadseroresponse between the 2 age groups (children - young adult) was 0.0% (2-sided 95% CI: -2.0%,2.2%). This information is presented in Table 10.

Table 10. Summary of geometric mean ratio for 50% neutralising titre and difference inpercentages of participants with seroresponse - comparison of children 5 to 11 yearsof age (Study 3) to participants 16 to 25 years of age (Study 2) - participants withoutevidence of infection up to 1 month after Dose 2 - immunobridging subset -

Phase 2/3 - evaluable immunogenicity population

COVID-19 mRNA Vaccine10 mcg/dose 30 mcg/dose5 to 11 years 16 to 25 years 5 to 11 years/

Na=264 Na=253 16 to 25 years

Metimmunobridging

Time GMTc GMTc GMRd objectiveepointb (95% CIc) (95% CIc) (95% CId) (Y/N)

Geometricmean 50% 1 monthneutralising after 1 197.6 1 146.5 1.04titref (GMTc) Dose 2 (1 106.1, 1 296.6) (1 045.5, 1 257.2) (0.93, 1.18) Y

Met

Difference immunobridging

Time ng (%) ng (%) %i objectivekpointb (95% CIh) (95% CIh) (95% CIj) (Y/N)

Seroresponserate (%) for50% 1 monthneutralising after 262 (99.2) 251 (99.2) 0.0titref Dose 2 (97.3, 99.9) (97.2, 99.9) (-2.0, 2.2) Y

Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titre;

LLOQ = lower limit of quantitation; NAAT = nucleic acid amplification test; NT50 = 50% neutralising titre;

SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

Note: Participants who had no serological or virological evidence (up to 1 month post-Dose 2 blood samplecollection) of past SARS-CoV-2 infection (i.e. N-binding antibody [serum] negative at Dose 1 visit and 1 monthafter Dose 2, SARS-CoV-2 not detected by NAAT [nasal swab] at Dose 1 and Dose 2 visits, and negative NAAT(nasal swab) at any unscheduled visit up to 1 month after Dose 2 blood collection) and had no medical history of

COVID-19 were included in the analysis.

Note: Seroresponse is defined as achieving a ≥ 4-fold rise from baseline (before Dose 1). If the baselinemeasurement is below the LLOQ, a post-vaccination assay result ≥ 4 × LLOQ is considered a seroresponse.

a. N = Number of participants with valid and determinate assay results before vaccination and at 1 month after

Dose 2. These values are also the denominators used in the percentage calculations for seroresponse rates.

b. Protocol-specified timing for blood sample collection.

c. GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titres and thecorresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to0.5 × LLOQ.

d. GMRs and 2-sided 95% CIs were calculated by exponentiating the mean difference of the logarithms of thetitres (5 to 11 years of age minus 16 to 25 years of age) and the corresponding CI (based on the Student tdistribution).

e. Immunobridging based on GMT is declared if the lower bound of the 2-sided 95% CI for the GMR is greaterthan 0.67 and the point estimate of the GMR is ≥ 0.8.

f. SARS-CoV-2 NT50 were determined using the SARS-CoV-2 mNeonGreen Virus Microneutralisation

Assay. The assay uses a fluorescent reporter virus derived from the USA_WA1/2020 strain and virusneutralisation is read on Vero cell monolayers. The sample NT50 is defined as the reciprocal serum dilutionat which 50% of the virus is neutralised.

g. n = Number of participants with seroresponse based on NT50 1 month after Dose 2.h. Exact 2-sided CI based on the Clopper and Pearson method.i. Difference in proportions, expressed as a percentage (5 to 11 years of age minus 16 to 25 years of age).j. 2-Sided CI, based on the Miettinen and Nurminen method for the difference in proportions, expressed as apercentage.k. Immunobridging based on seroresponse rate is declared if the lower bound of the 2-sided 95% CI for theseroresponse difference is greater than -10.0%.

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

Effectiveness of a booster dose of Comirnaty was based on an assessment of 50% neutralizingantibody titres (NT50) against SARS-CoV-2 (USA_WA1/2020) in Study 2. In this study, the boosterdose was administered 5 to 8 months (median 7 months) after the second dose. In Study 2, analyses of

NT50 1 month after the booster dose compared to 1 month after the primary series in individuals 18 to55 years of age who had no serological or virological evidence of past SARS-CoV-2 infection up to1 month after the booster vaccination demonstrated noninferiority for both geometric mean ratio(GMR) and difference in seroresponse rates. Seroresponse for a participant was defined as achieving a≥ 4-fold rise in NT50 from baseline (before primary series). These analyses are summarised in

Table 11.

Table 11. SARS-CoV-2 neutralization assay - NT50 (titre)† (SARS-CoV-2 USA_WA1/2020) -

GMT and seroresponse rate comparison of 1 month after booster dose to 1 monthafter primary series - participants 18 to 55 years of age without evidence of infectionup to 1 month after booster dose* - booster dose evaluable immunogenicitypopulation±1 month afterbooster dose - Met1 month after 1 month after 1 month after noninferioritybooster dose primary series primary series objectiven (95% CI) (95% CI) (97.5% CI) (Y/N)

Geometric mean50% neutralizing 2 466.0b 755.7b 3.26ctitre (GMTb) 212a (2 202.6, 2 760.8) (663.1, 861.2) (2.76, 3.86) Yd

Seroresponse rate 199f 190f(%) for 50% 99.5% 95.0% 4.5%gneutralizing titre† 200e (97.2%, 100.0%) (91.0%, 97.6%) (1.0%, 7.9%h) Yi

Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titre;

LLOQ = lower limit of quantitation; N-binding = SARS-CoV-2 nucleoprotein-binding; NAAT = nucleic acidamplification test; NT50 = 50% neutralizing titre; SARS-CoV-2 = severe acute respiratory syndromecoronavirus 2; Y/N = yes/no.† SARS-CoV-2 NT50 were determined using the SARS-CoV-2 mNeonGreen Virus Microneutralization Assay.

The assay uses a fluorescent reporter virus derived from the USA_WA1/2020 strain and virus neutralization isread on Vero cell monolayers. The sample NT50 is defined as the reciprocal serum dilution at which 50% ofthe virus is neutralised.

* Participants who had no serological or virological evidence (up to 1 month after receipt of a booster dose of

Comirnaty) of past SARS-CoV-2 infection (i.e. N-binding antibody [serum] negative and SARS-CoV-2 notdetected by NAAT [nasal swab]) and had a negative NAAT (nasal swab) at any unscheduled visit up to1 month after the booster dose were included in the analysis.

± All eligible participants who had received 2 doses of Comirnaty as initially randomised, with Dose 2 receivedwithin the predefined window (within 19 to 42 days after Dose 1), received a booster dose of Comirnaty, hadat least 1 valid and determinate immunogenicity result after booster dose from a blood collection within anappropriate window (within 28 to 42 days after the booster dose), and had no other important protocoldeviations as determined by the clinician.

a. n = Number of participants with valid and determinate assay results at both sampling time points withinspecified window.

b. GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titres and thecorresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to0.5 × LLOQ.

c. GMRs and 2-sided 97.5% CIs were calculated by exponentiating the mean differences in the logarithms of theassay and the corresponding CIs (based on the Student t distribution).

d. Noninferiority is declared if the lower bound of the 2-sided 97.5% CI for the GMR is > 0.67 and the pointestimate of the GMR is ≥ 0.80.

e. n = Number of participants with valid and determinate assay results for the specified assay at baseline,1 month after Dose 2 and 1 month after the booster dose within specified window. These values are thedenominators for the percentage calculations.

f. Number of participants with seroresponse for the given assay at the given dose/sampling time point. Exact2-sided CI based on the Clopper and Pearson method.

g. Difference in proportions, expressed as a percentage (1 month after booster dose - 1 month after Dose 2).h. Adjusted Wald 2-sided CI for the difference in proportions, expressed as a percentage.

i. Noninferiority is declared if the lower bound of the 2-sided 97.5% CI for the percentage difference is > -10%.

Relative vaccine efficacy in participants 16 years of age and older - after booster dose

An interim efficacy analysis of Study 4, a placebo-controlled booster study performed inapproximately 10 000 participants 16 years of age and older who were recruited from Study 2,evaluated confirmed COVID-19 cases accrued from at least 7 days after booster vaccination up to adata cut-off date of 5 October 2021, which represents a median of 2.5 months post-booster follow-up.

The booster dose was administered 5 to 13 months (median 11 months) after the second dose. Vaccineefficacy of the Comirnaty booster dose after the primary series relative to the placebo booster groupwho only received the primary series dose was assessed.

The relative vaccine efficacy information for participants 16 years of age and older without priorevidence of SARS-CoV-2 infection is presented in Table 12. Relative vaccine efficacy in participantswith or without evidence of prior SARS-CoV-2 infection was 94.6% (95% confidence interval of88.5% to 97.9%), similar to that seen in those participants without evidence of prior infection. Primary

COVID-19 cases observed from 7 days after booster vaccination were 7 primary cases in the

Comirnaty group, and 124 primary cases in the placebo group.

Table 12. Vaccine efficacy - First COVID-19 occurrence from 7 days after boostervaccination - participants 16 years of age and older without evidence ofinfection - evaluable efficacy population

First COVID-19 occurrence from 7 days after booster dose in participants without evidence ofprior SARS-CoV-2 infection*

Comirnaty Placebo

Na=4 695 Na=4 671

Cases Cases Relative Vaccinen1b n1b Efficacye %

Surveillance Timec (n2d) Surveillance Timec (n2d) (95% CIf)

First COVID-19occurrence from 7 daysafter booster 6 123 95.3vaccination 0.823 (4 659) 0.792 (4 614) (89.5, 98.3)

Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and atleast 1 symptom consistent with COVID-19 (symptoms included: fever; new or increased cough; new orincreased shortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat;diarrhoea; vomiting).

* Participants who had no serological or virological evidence (prior to 7 days after receipt of the boostervaccination) of past SARS-CoV-2 infection (i.e. N-binding antibody [serum] negative at Visit 1 and

SARS-CoV-2 not detected by NAAT [nasal swab] at Visit 1, and had a negative NAAT [nasal swab] at anyunscheduled visit prior to 7 days after booster vaccination) were included in the analysis.

a. N = Number of participants in the specified group.

b. n1 = Number of participants meeting the endpoint definition.

c. Total surveillance time in 1 000 person-years for the given endpoint across all participants within each groupat risk for the endpoint. Time period for COVID-19 case accrual is from 7 days after the booster vaccinationto the end of the surveillance period.

d. n2 = Number of participants at risk for the endpoint.

e. Relative vaccine efficacy of the Comirnaty booster group relative to the placebo group (non-booster).

f. Two-sided confidence interval (CI) for relative vaccine efficacy is derived based on the Clopper and Pearsonmethod adjusted for surveillance time.

Immunogenicity in children 5 to 11 years of age (i.e. 5 to less than 12 years of age) - after boosterdose

A booster dose of Comirnaty was given to 401 randomly selected participants in Study 3.

Effectiveness of a booster dose in ages 5 to 11 is inferred by immunogenicity. The immunogenicity ofthis was assessed through NT50 against the reference strain of SARS-CoV-2 (USA_WA1/2020).

Analyses of NT50 1 month after the booster dose compared to before the booster dose demonstrated asubstantial increase in GMTs in individuals 5 to 11 years of age who had no serological or virologicalevidence of past SARS-CoV-2 infection up to 1 month after the dose 2 and the booster dose. Thisanalysis is summarised in Table 13.

Table 13. Summary of geometric mean titres - NT50 - participants without evidence ofinfection - phase 2/3 - immunogenicity set - 5 to 11 years of age - evaluableimmunogenicity population

Sampling time pointa1 month after booster1 month after booster 1 month after dose 2 dose/dose (nb=67) (nb=96) 1 month after dose 2

GMTc GMTc GMRd

Assay (95% CIc) (95% CIc) (95% CId)

SARS-CoV-2neutralisationassay - NT50 2 720.9 1 253.9 2.17(titre) (2 280.1, 3 247.0) (1 116.0, 1 408.9) (1.76, 2.68)

Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titre;

LLOQ = lower limit of quantitation; NT50 = 50% neutralising titre; SARS-CoV-2 = severe acute respiratorysyndrome coronavirus 2.

a. Protocol-specified timing for blood sample collection.

b. n = Number of participants with valid and determinate assay results for the specified assay at the givendose/sampling time point.

c. GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titres and thecorresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to0.5 × LLOQ.

d. GMRs and 2-sided 95% CIs were calculated by exponentiating the mean difference of the logarithms of thetitres (1-Month Post-Booster Dose minus 1-Month Post-Dose 2) and the corresponding CI (based on the

Student t distribution).

Immunogenicity of a booster dose following primary vaccination with another authorised COVID-19vaccine

Effectiveness of a Comirnaty booster dose (30 mcg) in individuals who completed primaryvaccination with another authorised COVID-19 vaccine (heterologous booster dose) is inferred fromimmunogenicity data from an independent National Institutes of Health (NIH) study phase 1/2open-label clinical trial (NCT04889209) conducted in the United States. In this study, adults (range 19to 80 years of age) who had completed primary vaccination with Moderna 100 mcg 2-dose series(N = 51, mean age 54±17), Janssen single dose (N = 53, mean age 48±14), or Comirnaty 30 mcg2-dose series (N = 50, mean age 50±18) at least 12 weeks prior to enrolment and who reported nohistory of SARS-CoV-2 infection received a booster dose of Comirnaty (30 mcg). The boost with

Comirnaty induced a 36, 12, and 20 GMR-fold rise in neutralising titres following the Janssen,

Moderna, and Comirnaty primary doses, respectively.

Heterologous boosting with Comirnaty was also evaluated in the CoV-BOOST study(EudraCT 2021-002175-19), a multicentre, randomised, controlled, phase 2 trial of third dose boostervaccination against COVID-19, in which 107 adult participants (median age 71 years of age,interquartile range 54 to 77 years of age) were randomised at least 70 days post 2 doses of

AstraZeneca COVID-19 Vaccine. After the AstraZeneca COVID‑19 Vaccine primary series,pseudovirus (wild-type), neutralising antibody NT50 GMR-fold change increased 21.6-fold withheterologous Comirnaty booster (n = 95).

Immunogenicity in participants > 55 years of age - after a booster dose (fourth dose) of Comirnaty(30 mcg)

In an interim analysis of a subset from Study 4 (Substudy E), 305 participants > 55 years of age whohad completed a series of 3 doses of Comirnaty received Comirnaty (30 mcg) as a booster dose (fourthdose) 5 to 12 months after receiving Dose 3. For the Immunogenicity subset data see Table 8.

Immunogenicity in participants 18 to ≤ 55 years of age - after a booster dose (fourth dose) of

Comirnaty (30 mcg)

In Substudy D [a subset from Study 2 (Phase 3) and Study 4 (Phase 3)], 325 participants 18 to≤ 55 years of age who had completed 3 doses of Comirnaty received Comirnaty (30 mcg) as a boosterdose (fourth dose) 90 to 180 days after receiving Dose 3. For the Immunogenicity subset data see

Table 14.

Table 14. Summary of immunogenicity data from participants in C4591031 Substudy D(cohort 2 full expanded set) and Substudy E (expanded cohort immunogenicitysubset) who received Comirnaty 30 mcg as booster (fourth dose) - participantswithout evidence of infection up to 1 month after booster dose - evaluableimmunogenicity population

Dose/ Substudy D Substudy Esampling time (18 to ≤ 55 years of age) (> 55 years of age)pointa Comirnaty 30 mcg Comirnaty 30 mcg

GMT GMT

GMT Nb (95% CId) Nb (95% CId)

SARS-CoV-2 315.0 67.5neutralization assay - 1/Prevax 226 (269.0, 368.9) 167 (52.9, 86.3)

Omicron BA.1 - NT50 1 063.2 455.8(titre) 1/1 Month 228 (935.8, 1 207.9) 163 (365.9, 567.6)

SARS-CoV-2 3 999.0 1 389.1neutralization assay - 1/Prevax 226 (3 529.5, 4 531.0) 179 (1 142.1, 1 689.5)reference strain - NT50 12 009.9 5 998.1(titre) 1/1 Month 227 (10 744.3, 13 424.6) 182 (5 223.6, 6 887.4)

Seroresponse rate at ne (%) ne (%)1 month post-Dose 4 Nc (95% CIf) Nc (95% CIf)

SARS-CoV-2neutralization assay -

Omicron BA.1 - NT50 91 (40.3%) 85 (57.0%)(titre) 1/1 Month 226 (33.8, 47.0) 149 (48.7, 65.1)

SARS-CoV-2neutralization assay -reference strain - NT50 76 (33.8%) 88 (49.2%)(titre) 1/1 Month 225 (27.6, 40.4) 179 (41.6, 56.7)

Abbreviations: CI = confidence interval; GMT = geometric mean titre; LLOQ = lower limit of quantitation;

N-binding = SARS-CoV-2 nucleoprotein-binding; NAAT = nucleic acid amplification test; NT50 = 50%neutralising titre; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

Note: Median time from Dose 3 to Dose 4 of Comirnaty 30 mcg is 4.0 months for Substudy D Cohort 2 and6.3 months for Substudy E expanded cohort.

Note: Substudy D Full Expanded Set = Cohort 2 excluding the sentinel group; Substudy E Immunogenicity

Subset = a random sample of 230 participants in each vaccine group selected from the expanded cohort.

Note: Participants who had no serological or virological evidence (prior to the 1-month post-study vaccinationblood sample collection) of past SARS-CoV-2 infection (i.e. N-binding antibody [serum] result negative at thestudy vaccination and the 1-month post-study vaccination visits, negative NAAT [nasal swab] result at the studyvaccination visit, and any unscheduled visit prior to the 1-month post-study vaccination blood sample collection)and had no medical history of COVID-19 were included in the analysis.

Note: Seroresponse is defined as achieving ≥ 4-fold rise from baseline (before the study vaccination). If thebaseline measurement is below the LLOQ, the post-vaccination measure of ≥ 4 × LLOQ is considered aseroresponse.

a. Protocol-specified timing for blood sample collection.

b. N = Number of participants with valid and determinate assay results for the specified assay at the givensampling time point.

c. N = Number of participants with valid and determinate assay results for the specified assay at both thepre-vaccination time point and the given sampling time point.

d. GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titres and thecorresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to0.5 × LLOQ.

e. n = Number of participants with seroresponse for the given assay at the given sampling time point.

f. Exact 2-sided CI, based on the Clopper and Pearson method.

Immunogenicity in pregnant participants and infants born to pregnant participants - after 2 doseswith Comirnaty

Study 9 was a Phase 2/3 multinational, placebo-controlled, observer-blind study that enrolled pregnantparticipants 18 years of age and older to receive 2 doses of Comirnaty (n = 173) or placebo (n = 173).

Pregnant participants received Dose 1 of Comirnaty at 24 to 34 weeks gestation and the majority(90.2%) received the second dose 19 to 23 days after Dose 1.

Descriptive immunogenicity analysis was performed in pregnant participants receiving Comirnaty in

Study 9 compared to a comparator subset of nonpregnant participants from Study 2 evaluating theratio of the neutralising GMT (GMR) 1 month after Dose 2. The evaluable immunogenicity populationwho received Comirnaty in the pregnant participants group in Study 9 (n = 111) and in nonpregnantparticipants in Study 2 (n = 114) had a median age of 30 years (range 18 to 44 years of age) andcomprised of 37.8% vs 3.5% with a positive baseline SARS-CoV-2 status, respectively.

Among participants without prior evidence of SARS-CoV-2 infection up to 1 month after Dose 2, theobserved SARS-CoV-2 50% neutralizing GMT 1 month after Dose 2 was lower in the pregnantparticipants (Study 9) when compared to nonpregnant female participants (Study 2) (the ratio of the

GMT [GMR] was 0.67 (95% CI: 0.50, 0.90).

Among participants with or without prior evidence of SARS-CoV-2 infection up to 1 month after

Dose 2, the model-adjusted GMT 1 month after Dose 2 was similar in the pregnant participants whencompared to nonpregnant female participants (the model-adjusted ratio of the GMT [GMR] was 0.95(95% CI: 0.69, 1.30). The model-adjusted GMT and GMR were calculated based on a regressionmodel adjusting for age and baseline neutralizing titres.

Immunogenicity in immunocompromised participants (adults and children)

Study 10 is a Phase 2b, open-label study (n = 124) that enrolled immunocompromised participants 2 to< 18 years of age receiving immunomodulator therapy or who have undergone solid organ transplant(within the previous 3 months) and are on immunosuppression or who have undergone bone marrowor stem cell transplant at least 6 months prior to enrolment and in immunocompromised participants18 years of age and older treated for non-small cell lung cancer (NSCLC) or chronic lymphocyticleukaemia (CLL), receiving haemodialysis for secondary to end-stage renal disease, or receivingimmunomodulator therapy for an autoimmune inflammatory disorder. Participants received4 age-appropriate doses of Comirnaty (3 mcg, 10 mcg, or 30 mcg); the first 2 doses separated by21 days, with the third dose occurring 28 days after the second dose, followed by a fourth dose, 3 to6 months after Dose 3.

Analysis of immunogenicity data at 1 month after Dose 3 (26 participants 2 to < 5 years of age,56 participants 5 to < 12 years of age, 11 participants 12 to < 18 years of age, and 4 participants≥ 18 years of age) and 1 month after Dose 4 (16 participants 2 to < 5 years of age, 31 participants 5 to< 12 years of age, 6 participants 12 to < 18 years of age, and 4 participants ≥ 18 years of age) in theevaluable immunogenicity population without evidence of prior infection demonstrated avaccine-elicited immune response. GMTs were observed to be substantially higher at 1 month after

Dose 3 and further increased at 1 month after Dose 4 and remained high at 6 months after Dose 4compared to levels observed before study vaccination across age groups and disease subsets.

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

Comirnaty in the paediatric population in prevention of COVID-19 (see section 4.2 for information onpaediatric use).

Not applicable.

Non-clinical data reveal no special hazard for humans based on conventional studies of repeat dosetoxicity and reproductive and developmental toxicity.

Rats intramuscularly administered Comirnaty (receiving 3 full human doses once weekly, generatingrelatively higher levels in rats due to body weight differences) demonstrated some injection siteoedema and erythema and increases in white blood cells (including basophils and eosinophils)consistent with an inflammatory response as well as vacuolation of portal hepatocytes withoutevidence of liver injury. All effects were reversible.

Neither genotoxicity nor carcinogenicity studies were performed. The components of the vaccine (lipidsand mRNA) are not expected to have genotoxic potential.

Reproductive and developmental toxicity were investigated in rats in a combined fertility anddevelopmental toxicity study where female rats were intramuscularly administered Comirnaty prior tomating and during gestation (receiving 4 full human doses that generate relatively higher levels in ratdue to body weight differences, spanning between pre-mating day 21 and gestational day 20).

SARS-CoV-2 neutralising antibody responses were present in maternal animals from prior to matingto the end of the study on post-natal day 21 as well as in foetuses and offspring. There were novaccine-related effects on female fertility, pregnancy, or embryo-foetal or offspring development. No

Comirnaty data are available on vaccine placental transfer or excretion in milk.

((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) (ALC-0315)2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide (ALC-0159)1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC)

Cholesterol

Trometamol

Trometamol hydrochloride

Sucrose

Water for injections

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

Vials

The vaccine will be received frozen at -90 °C to -60 °C.

Frozen vaccine can be stored either at -90 °C to -60 °C or 2 °C to 8 °C upon receipt.

18 months when stored at -90 °C to -60 °C.

Within the 18-month shelf life the thawed (previously frozen) vials may be stored at 2 °C to 8 °C forup to 10 weeks.

Thawing procedure

Single dose vials

When stored frozen at −90 °C to −60 °C, 10-vial packs of single dose vials of the vaccine can bethawed at 2 °C to 8 °C for 2 hours or individual vials can be thawed at room temperature (up to 30 °C)for 30 minutes.

Multidose vials

When stored frozen at −90 °C to −60 °C, 10-vial packs of multidose vials of the vaccine can bethawed at 2 °C to 8 °C for 6 hours or individual vials can be thawed at room temperature (up to 30 °C)for 30 minutes.

Thawed (previously frozen) vials10 weeks storage and transportation at 2 °C to 8 °C within the 18-month shelf life.

* Upon moving the vaccine to 2 °C to 8 °C storage, the updated expiry date must be written onthe outer carton and the vaccine should be used or discarded by the updated expiry date. Theoriginal expiry date should be crossed out.

* If the vaccine is received at 2 °C to 8 °C it should be stored at 2 °C to 8 °C. The expiry date onthe outer carton should have been updated to reflect the refrigerated expiry date and the originalexpiry date should have been crossed out.

Prior to use, the unopened vials can be stored for up to 12 hours at temperatures between 8 °C and30 °C.

Thawed vials can be handled in room light conditions.

Once thawed, the vaccine should not be re-frozen.

Handling of temperature excursions during refrigerated storage

* Stability data indicate that the unopened vial is stable for up to 10 weeks when stored attemperatures from −2 °C to 2 °C, within the 10-week storage period between 2 °C and 8 °C.

* Stability data indicate the vial can be stored for up to 24 hours at temperatures of 8 °C to 30 °C,including up to 12 hours following first puncture.

This information is intended to guide healthcare professionals only in case of temporary temperatureexcursion.

Opened vials

Chemical and physical in-use stability has been demonstrated for 12 hours at 2 ºC to 30 ºC, whichincludes up to 6 hours transportation time. From a microbiological point of view, unless the method ofopening precludes the risks of microbial contamination, the product should be used immediately. If notused immediately, in-use storage times and conditions are the responsibility of the user.

Pre-filled syringes

Confirm the storage conditions listed for the different types of pre-filled syringes.

Plastic pre-filled syringes

The vaccine will be received frozen at −90 °C to −60 °C.

Frozen vaccine can be stored either at −90 °C to −60 °C or 2 °C to 8 °C upon receipt.

12 months when stored at −90 °C to −60 °C.

Within the 12-month shelf life the thawed (previously frozen) pre-filled syringes may be stored at 2 °Cto 8 °C for up to 10 weeks.

Thawing procedure for plastic pre-filled syringes

Frozen 10-pack of pre-filled syringes should be thawed in the original carton at 2 °C to 8 °C for2 hours or at room temperature (up to 30 °C) for 60 minutes.

Thawed (previously frozen) plastic pre-filled syringes10 weeks storage and transport at 2 °C to 8 °C within the 12-month shelf life.

* Upon moving the vaccine to 2 °C to 8 °C storage, the updated expiry date must be written onthe outer carton and the vaccine should be used or discarded by the updated expiry date. Theoriginal expiry date should be crossed out.

* If the vaccine is received at 2 °C to 8 °C it should be stored at 2 °C to 8 °C. The expiry date onthe outer carton should have been updated to reflect the refrigerated expiry date and the originalexpiry date should have been crossed out.

Prior to use, thawed pre-filled syringes can be stored for up to 12 hours at temperatures between 8 °Cand 30 °C and can be handled in room light conditions.

Once thawed, the vaccine should not be re-frozen.

Handling of temperature excursions during refrigerated storage

The following information is intended to guide healthcare professionals only in case of temporarytemperature excursion.

If an individual frozen pre-filled syringe is thawed at room temperature (up to 30 °C) outside of thecarton, the pre-filled syringe should not be stored and should be used immediately.

Stability data indicate that the pre-filled syringe is stable for up to 10 weeks when stored attemperatures from −2 °C to 2 °C, within the 10-week storage period between 2 °C and 8 °C.

Glass pre-filled syringes

The vaccine will be received and stored at 2 °C to 8 °C (refrigerated only).8 months when stored at 2 °C to 8 °C.

Prior to use, pre-filled syringes can be stored for up to 12 hours at temperatures between 8 °C and30 °C and can be handled in room light conditions.

Vials and plastic pre-filled syringes

Store single dose vials, multidose vials and frozen plastic pre-filled syringes in a freezer at −90 °C to−60 °C.

Glass pre-filled syringes

Store glass pre-filled syringes at 2 °C to 8 °C. DO NOT FREEZE.

Vials and pre-filled syringes

Store the vaccine in the original package in order to protect from light.

During storage, minimise exposure to room light, and avoid exposure to direct sunlight and ultravioletlight.

For storage conditions after thawing and first opening, see section 6.3.

Table 15. Comirnaty Omicron XBB.1.5 nature and contents of container

Dose(s) percontainer(see sections

Product presentation Contents Container 4.2 and 6.6) Pack sizes

Supplied in a 2 mL Single dose

Comirnaty Omicron clear vial (type I vial 1 dose of

XBB.1.5 glass) with a stopper (grey cap) 0.3 mL 10 vials30 micrograms/dose (synthetic bromobutyldispersion for rubber) and a grey Multidoseinjection flip-off plastic cap (2.25 mL) vial 6 doses of 10 vials or0.3 mL 195 vialswith aluminium seal. (grey cap)

Supplied in a single 1 mL long

Comirnaty Omicron dose pre-filled syringe cyclic-olefin

XBB.1.5 with plunger stopper copolymer30 micrograms/dose (synthetic bromobutyl plastic syringe 1 dose of 10 pre-filleddispersion for rubber) and a tip cap 0.3 mL syringesinjection in pre-filled (synthetic bromobutyl Type I glasssyringe rubber) without syringeneedle.

Supplied in a 2 mL Single dose

Comirnaty Omicron clear vial (type I vial 1 dose of 10 vials

XBB.1.5 glass) with a stopper (blue cap) 0.3 mL10 micrograms/dose (synthetic bromobutyldispersion for rubber) and a blue Multidose 6 doses ofinjection flip-off plastic cap (2.25 mL) vial 0.3 mL 10 vialswith aluminium seal. (blue cap)

Not all pack sizes may be marketed.

Handling instructions prior to use

Comirnaty Omicron XBB.1.5 should be prepared by a healthcare professional using aseptic techniqueto ensure the sterility of the prepared dispersion.

Instructions applicable to single dose and multidose vials

* Verify that the vial has either:

− a grey plastic cap and the product name is Comirnaty Omicron XBB.1.530 micrograms/dose dispersion for injection (12 years and older), or− a blue plastic cap and the product name is Comirnaty Omicron XBB.1.510 micrograms/dose dispersion for injection (children 5 to 11 years).

* If the vial has another product name on the label, please make reference to the Summary of

Product Characteristics for that formulation.

* If the vial is stored frozen it must be thawed prior to use. Frozen vials should be transferred toan environment of 2 °C to 8 °C to thaw. Ensure vials are completely thawed prior to use.− Single dose vials: A 10-vial pack of single dose vials may take 2 hours to thaw.− Multidose vials: A 10-vial pack of multidose vials may take 6 hours to thaw.

* Upon moving vials to 2 °C to 8 °C storage, update the expiry date on the carton.

* Unopened vials can be stored for up to 10 weeks at 2 °C to 8 °C; not exceeding the printedexpiry date (EXP).

* Alternatively, individual frozen vials may be thawed for 30 minutes at temperatures up to 30 °C.

* Prior to use, the unopened vial can be stored for up to 12 hours at temperatures up to 30 °C.

Thawed vials can be handled in room light conditions.

Preparation of 0.3 mL doses

* Gently mix by inverting vials 10 times prior to use. Do not shake.

* Prior to mixing, the thawed dispersion may contain white to off-white opaque amorphousparticles.

* After mixing, the vaccine should present as a:

− Grey cap: white to off-white dispersion with no particulates visible.− Blue cap: clear to slightly opalescent dispersion with no particulates visible.

* Do not use the vaccine if particulates or discolouration are present.

* Check whether the vial is a single dose vial or a multidose vial and follow the applicablehandling instructions below:− Single dose vials Withdraw a single 0.3 mL dose of vaccine. Discard vial and any excess volume.

− Multidose vials Multidose vials contain 6 doses of 0.3 mL each. Using aseptic technique, cleanse the vial stopper with a single use antiseptic swab. Withdraw 0.3 mL of Comirnaty Omicron XBB.1.5. Low dead-volume syringes and/or needles should be used in order to extract6 doses from a single vial. The low dead-volume syringe and needle combinationshould have a dead-volume of no more than 35 microlitres. If standard syringes andneedles are used, there may not be sufficient volume to extract a sixth dose from asingle vial.

 Each dose must contain 0.3 mL of vaccine. If the amount of vaccine remaining in the vial cannot provide a full dose of0.3 mL, discard the vial and any excess volume. Record the appropriate date/time on the multidose vial. Discard any unused vaccine12 hours after first puncture.

Instructions applicable to pre-filled syringes

Plastic pre-filled syringes

* Frozen pre-filled syringes must be completely thawed prior to use.

− A 10 pre-filled syringe pack can be thawed at 2 °C to 8 °C. It may take 2 hours to thaw.− Alternatively, a carton of 10 frozen pre-filled syringes may be thawed for 60 minutes atroom temperature (up to 30 °C).

* If an individual pre-filled syringe is thawed outside the carton at room temperature (up to30 °C), this must be used immediately.

* Upon moving the pre-filled syringes to 2 °C to 8 °C storage, update the expiry date on thecarton. If received at 2 °C to 8 °C, check that the expiry date has been updated.

* Thawed (previously frozen) pre-filled syringes can be stored for up to 10 weeks at 2 °C to 8 °C;not exceeding the printed expiry date (EXP). Once thawed, the vaccine cannot be re-frozen.

* Prior to use, the thawed pre-filled syringes can be stored for up to 12 hours at temperaturesbetween 8 °C to 30 °C and can be handled in room light conditions.

* Remove tip cap by slowly turning the cap counterclockwise. Do not shake. Attach a needleappropriate for intramuscular injection and administer the entire volume.

Glass pre-filled syringes

* Prior to use, pre-filled syringes can be stored for up to 12 hours at temperatures between 8 °C to30 °C and can be handled in room light conditions.

* Remove tip cap by slowly turning the cap counterclockwise. Do not shake. Attach a needleappropriate for intramuscular injection and administer the entire volume.

Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.

BioNTech Manufacturing GmbH

An der Goldgrube 1255131 Mainz

Germany

Phone: +49 6131 9084-0

Fax: +49 6131 9084-2121service@biontech.de

Table 16. Comirnaty Omicron XBB.1.5 marketing authorisation numbers

Marketing

Product presentation Container authorisation number

Comirnaty Omicron XBB.1.5 30 micrograms/dose Single dose vials EU/1/20/1528/018dispersion for injection Multidose vials EU/1/20/1528/019

EU/1/20/1528/020

Comirnaty Omicron XBB.1.5 30 micrograms/dose Plastic pre-filled syringes EU/1/20/1528/025dispersion for injection in pre-filled syringe Glass pre-filled syringes EU/1/20/1528/027

Comirnaty Omicron XBB.1.5 10 micrograms/dose Single dose vials EU/1/20/1528/022dispersion for injection Multidose vials EU/1/20/1528/023

Date of first authorisation: 21 December 2020

Date of latest renewal: 10 October 2022

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

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