SPIKEVAX LP.8.1 INJECTION DISPERSION 50mcg / dose dispersion for injection medication leaflet

Spikevax LP.8.1 0.1 mg/mL dispersion for injection

Spikevax LP.8.1 50 micrograms dispersion for injection in pre-filled syringe

Spikevax LP.8.1 25 micrograms dispersion for injection in pre-filled syringe

COVID-19 mRNA Vaccine

Table 1. Spikevax LP.8.1 qualitative and quantitative composition

Strength Container Dose(s) Composition per dose

Spikevax LP.8.1 0.1 mg/mL Multidose 5 doses One dose (0.5 mL) containsdispersion for injection 2.5 mL vial of 50 micrograms of(blue flip-off 0.5 mL SARS-CoV-2 LP.8.1 mRNA, acap) each or COVID-19 mRNA Vaccine10 doses (nucleoside modified)of 0.25 (embedded in lipidmL each nanoparticles).

One dose (0.25 mL) contains25 micrograms of

SARS-CoV-2 LP.8.1 mRNA, a

COVID-19 mRNA Vaccine(nucleoside modified)(embedded in lipidnanoparticles).

Spikevax LP.8.1 50 micrograms Pre-filled 1 dose of One dose (0.5 mL) containsdispersion for injection in pre-filled syringe 0.5 mL 50 micrograms ofsyringe SARS-CoV-2 LP.8.1 mRNA, a

For COVID-19 mRNA Vaccinesingle- (nucleoside modified)use only. (embedded in lipidnanoparticles).

Spikevax LP.8.1 25 micrograms Pre-filled 1 dose of One dose (0.25 mL) containsdispersion for injection in pre-filled syringe 0.25 mL 25 micrograms ofsyringe SARS-CoV-2 LP.8.1 mRNA, a

For COVID-19 mRNA Vaccinesingle- (nucleoside modified)use only. (embedded in lipidnanoparticles).

SARS-CoV-2 LP.8.1 mRNA is a single-stranded, 5’-capped messenger RNA (mRNA) produced usinga cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S)protein of SARS-CoV-2 (LP.8.1).

For the full list of excipients, see section 6.1.

Dispersion for injection

White to off white dispersion (pH: 7.0 - 8.0).

Spikevax LP.8.1 is indicated for active immunisation to prevent COVID-19 caused by SARS-CoV-2in individuals 6 months of age and older (see sections 4.2 and 5.1).

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

Table 2. Spikevax LP.8.1 posology

Age(s) Dose Additional recommendations

Children 6 months through Two doses of 0.25 mL Administer the second dose 28 days4 years of age, without prior each, given after the first dose (see sections 4.4vaccination and no known intramuscularly* and 5.1).history of SARS CoV-2infection If a child has received one priordose of any Spikevax vaccine, onedose of Spikevax LP.8.1 should beadministered to complete thetwo-dose series.

Children 6 months through One dose of 0.25 mL, given4 years of age, with prior intramuscularly*vaccination or known historyof SARS-CoV-2 infection

Spikevax LP.8.1 should be

Children 5 years through One dose of 0.25 mL, given administered at least 3 months after11 years of age, with or intramuscularly* the most recent dose of awithout prior vaccination COVID-19 vaccine.

Individuals 12 years of age One dose of 0.5 mL, givenand older, with or without intramuscularlyprior vaccination

Individuals 65 years of age One dose of 0.5 mL, given One additional dose may beand older intramuscularly administered at least 3 months afterthe most recent dose of a

COVID-19 vaccine.

* Do not use the 0.5 mL pre-filled syringe to deliver a partial volume of 0.25 mL.

Table 3. Spikevax LP.8.1 posology for immunocompromised individuals

Age(s) Dose Additional recommendations

Immunocompromised Two doses of 0.25 mL, A third dose in severelychildren 6 months through given intramuscularly* immunocompromised may be given4 years of age, without prior at least 28 days after the secondvaccination dose.

Immunocompromised One dose of 0.25 mL, givenchildren 6 months through intramuscularly*4 years of age, with priorvaccination Additional age-appropriate dose(s)may be administered in severely

Immunocompromised One dose of 0.25 mL, given immunocompromised at leastchildren 5 years through intramuscularly* 2 months following the most recent11 years of age, with or dose of a COVID-19 vaccine at thewithout prior vaccination discretion of the healthcare provider,taking into consideration the

Immunocompromised One dose of 0.5 mL, given individual’s clinical circumstances.individuals 12 years of age intramuscularlyand older, with or withoutprior vaccination

* Do not use the 0.5 mL pre-filled syringe to deliver a partial volume of 0.25 mL.

The safety and efficacy of Spikevax in children less than 6 months of age have not yet beenestablished (see section 5.1).

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

The vaccine should be administered intramuscularly. The preferred site is the deltoid muscle of theupper arm.

Do not administer this 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.

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.

Anaphylaxis has been reported in individuals who have received Spikevax. Appropriate medicaltreatment and supervision should always be readily available in case of an anaphylactic reactionfollowing administration of the vaccine.

Close observation for at least 15 minutes is recommended following vaccination. Subsequent doses of

Spikevax LP.8.1 should not be given to those who have experienced anaphylaxis to a prior dose of any

Spikevax vaccine.

There is an increased risk for myocarditis and pericarditis following vaccination with Spikevax.

These conditions can develop within just a few days after vaccination, and have primarily occurredwithin 14 days. They have been observed more often in younger males, and more often after thesecond dose compared to the first dose (see section 4.8).

Available data indicate that most cases recover. Some cases required intensive care support and fatalcases have been observed.

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

Vaccinees should be instructed to seek immediate medical attention if they develop symptomsindicative of myocarditis or pericarditis such as (acute and persisting) chest pain, 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 may occur in association with vaccination as a psychogenic response to the needle injection.

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

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.

A few cases of capillary leak syndrome (CLS) flare-ups have been reported in the first days aftervaccination with Spikevax (original). Healthcare professionals should be aware of signs and symptomsof CLS to promptly recognise and treat the condition. In individuals with a medical history of CLS,planning of vaccination should be made in collaboration with appropriate medical experts.

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

As with all vaccines, vaccination with Spikevax LP.8.1 may not protect all vaccine recipients.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially‘sodium-free’.

Spikevax (including variant formulations) can be concomitantly administered with influenza vaccines(standard and high-dose) and with herpes zoster (shingles) subunit vaccine.

Different injectable vaccines should be given at different injection sites.

A large amount of observational data from pregnant women vaccinated with Spikevax has not shownan increase in adverse pregnancy outcomes.

Since differences between products are confined to the spike protein sequence, and there are noclinically meaningful differences in reactogenicity, SARS-CoV-2 LP.8.1 mRNA can be used duringpregnancy.

No data are available yet regarding the use of SARS-CoV-2 LP.8.1 mRNA during breastfeeding.

However, no effects on the breastfed newborn/infant are anticipated since the systemic exposure of thebreastfeeding woman to the vaccine is negligible. Observational data from women who werebreastfeeding after vaccination with Spikevax (original) have not shown a risk for adverse effects inbreastfed newborns/infants. SARS-CoV-2 LP.8.1 mRNA can be used during breastfeeding.

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

SARS-CoV-2 LP.8.1 mRNA 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 Spikevax (original) was evaluated in a Phase 3 randomised, placebo-controlled,observer-blind clinical study conducted in the United States involving 30 351 participants 18 years ofage and older who received at least one dose of Spikevax (original) (n=15 185) or placebo (n=15 166)(NCT04470427). At the time of vaccination, the mean age of the population was 52 years (range18-95); 22 831 (75.2%) of participants were 18 to 64 years of age and 7 520 (24.8%) of participantswere 65 years of age and older.

The most frequently reported adverse reactions were pain at the injection site (92%), fatigue (70%),headache (64.7%), myalgia (61.5%), arthralgia (46.4%), chills (45.4%), nausea/vomiting (23%),axillary swelling/tenderness (19.8%), fever (15.5%), injection site swelling (14.7%) and redness(10%). Adverse reactions were usually mild or moderate in intensity and resolved within a few daysafter vaccination. A slightly lower frequency of reactogenicity events was associated with greater age.

Overall, there was a higher incidence of some adverse reactions in younger age groups: the incidenceof axillary swelling/tenderness, fatigue, headache, myalgia, arthralgia, chills, nausea/vomitingand fever was higher in adults aged 18 to < 65 years than in those aged 65 years and above.

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

Safety data for Spikevax (original) in adolescents were collected in a Phase 2/3 randomised,placebo-controlled, observer-blind clinical study with multiple parts conducted in the United States.

The first portion of the study involved 3 726 participants 12 through 17 years of age who received atleast one dose of Spikevax (original) (n=2 486) or placebo (n=1 240) (NCT04649151). Demographiccharacteristics were similar among participants who received Spikevax (original) and those whoreceived placebo.

The most frequent adverse reactions in adolescents 12 to 17 years of age were injection site pain(97%), headache (78%), fatigue (75%), myalgia (54%), chills (49%), axillary swelling/tenderness(35%), arthralgia (35%), nausea/vomiting (29%), injection site swelling (28%), injection site erythema(26%), and fever (14%).

This study transitioned to an open-label Phase 2/3 study in which 1 346 participants 12 years through17 years of age received a booster dose of Spikevax at least 5 months after the second dose of theprimary series. No additional adverse reactions were identified in the open-label portion of the study.

Safety data for Spikevax (original) in children were collected in a Phase 2/3 two-part randomised,observer-blind clinical study conducted in the United States and Canada (NCT04796896). Part 1 wasan open-label phase of the study for safety, dose selection, and immunogenicity and included380 participants 6 years through 11 years of age who received at least 1 dose (0.25 mL) of Spikevax(original). Part 2 was the placebo-controlled phase for safety and included 4 016 participants 6 yearsthrough 11 years of age who received at least one dose (0.25 mL) of Spikevax (original) (n=3 012) orplacebo (n=1 004). No participants in Part 1 participated in Part 2. Demographic characteristics weresimilar among participants who received Spikevax (original) and those who received placebo.

The most frequent adverse reactions in participants 6 years through 11 years of age followingadministration of the primary series (in Part 2) were injection site pain (98.4%), fatigue (73.1%),headache (62.1%), myalgia (35.3%), chills (34.6%), nausea/vomiting (29.3%), axillaryswelling/tenderness (27.0%), fever (25.7%), injection site erythema (24.0%), injection site swelling(22.3%), and arthralgia (21.3%).

The study protocol was amended to include an open-label booster dose phase that included1 294 participants 6 years through 11 years of age who received a booster dose of Spikevax at least6 months after the second dose of the primary series. No additional adverse reactions were identifiedin the open-label portion of the study.

A Phase 2/3 randomised, placebo-controlled, observer-blind study to evaluate the safety, tolerability,reactogenicity, and efficacy of Spikevax was conducted in the United States and Canada. This studyinvolved 10 390 participants 6 months through 11 years of age who received at least one dose of

Spikevax (n=7 798) or placebo (n=2 592).

The study enrolled children in 3 age groups: 6 years through 11 years; 2 years through 5 years; and6 months through 23 months. This paediatric study involved 6 388 participants 6 months through5 years of age who received at least one dose of Spikevax (n=4 791) or placebo (n=1 597).

Demographic characteristics were similar among participants who received Spikevax and those whoreceived placebo.

In this clinical study, the adverse reactions in participants 6 months through 23 months of agefollowing administration of the primary series were irritability/crying (81.5%), pain at the injectionsite (56.2%), sleepiness (51.1%), loss of appetite (45.7%), fever (21.8%), swelling at the injection site(18.4%), erythema at the injection site (17.9%), and axillary swelling/tenderness (12.2%).

The adverse reactions in participants 24 through 36 months of age following administration of theprimary series were pain at the injection site (76.8%), irritability/crying (71.0%), sleepiness (49.7%),loss of appetite (42.4%), fever (26.1%), erythema at the injection site (17.9%), swelling at theinjection site (15.7%), and axillary swelling/tenderness (11.5%).

The adverse reactions in participants 37 months through 5 years of age following administration of theprimary series were pain at the injection site (83.8%), fatigue (61.9%), headache (22.9%), myalgia(22.1%), fever (20.9%), chills (16.8%), nausea/vomiting (15.2%), axillary swelling/tenderness(14.3%), arthralgia (12.8%), erythema at the injection site (9.5%), and swelling at the injection site(8.2%).

The safety profile presented below is based on data generated in several placebo-controlled clinicalstudies:

- 30 351 adults ≥ 18 years of age

- 3 726 adolescents 12 through 17 years of age

- 4 002 children 6 years through 11 years of age

- 6 388 children aged 6 months through 5 years of age

- and post-marketing experience.

Adverse reactions reported are listed according to the following frequency convention:

Very common (≥1/10)

Common (≥1/100 to <1/10)

Uncommon (≥1/1 000 to <1/100)

Rare (≥1/10 000 to <1/1 000)

Very rare (<1/10 000)

Not known (cannot be estimated from the available data)

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness(Table 4).

Table 4. Adverse reactions from Spikevax clinical studies and post authorisation experience inchildren and individuals 6 months of age and older

MedDRA system organ class Frequency Adverse reactions

Blood and lymphatic system Very common Lymphadenopathy*disorders

Immune system disorders Rare Anaphylaxis

MedDRA system organ class Frequency Adverse reactions

Not known Hypersensitivity

Metabolism and nutrition disorders Very common Decreased appetite†

Psychiatric disorders Very common Irritability/crying†

Nervous system disorders Very common Headache

Sleepiness†

Uncommon Dizziness

Rare Acute peripheral facial paralysis‡

Hypoaesthesia

Paraesthesia

Cardiac disorders Very rare Myocarditis

Pericarditis

Gastrointestinal disorders Very common Nausea/vomiting

Common Diarrhoea

Uncommon Abdominal pain§

Skin and subcutaneous tissue Common  Rashdisorders Uncommon Urticaria¶

Rare Erythema multiforme

Not known Mechanical urticaria

Chronic urticaria

Musculoskeletal and connective Very common Myalgiatissue disorders Arthralgia

Reproductive system and breast Not known Heavy menstrual bleeding#disorders

General disorders Very common Injection site painand administration site conditions Fatigue

Chills

Injection site erythema

Common Injection site urticaria

Injection site rash

Delayed injection site reaction♠

Uncommon Injection site pruritus

Rare Facial swelling♥

Not known Extensive swelling of vaccinatedlimb

*Lymphadenopathy was captured as axillary lymphadenopathy on the same side as the injection site. Other lymph nodes(e.g., cervical, supraclavicular) were affected in some cases.† Observed in the paediatric population (6 months to 5 years of age).‡ Throughout the safety follow-up period, acute peripheral facial paralysis (or palsy) was reported by three participants in the

Spikevax (original) group and one participant in the placebo group. Onset in the vaccine groupparticipants was 22 days, 28 days, and 32 days after Dose 2.§ Abdominal pain was observed in the paediatric population (6 to 11 years of age): 0.2% in the Spikevax (original) group and0% in the placebo group.¶ Urticaria has been observed with either acute onset (within a few days after vaccination) or delayed onset (up toapproximately two weeks after vaccination).# Most cases appeared to be non-serious and temporary in nature.♠ Median time to onset was 9 days after the first injection, and 11 days after the second injection. Median duration was4 days after the first injection, and 4 days after the second injection.♥ There were two serious adverse events of facial swelling in vaccine recipients with a history of injection of dermatologicalfillers. The onset of swelling was reported on Day 1 and Day 3, respectively, relative to day of vaccination.

The reactogenicity and safety profile in 343 subjects receiving Spikevax (original), that wereseropositive for SARS-CoV-2 at baseline, was comparable to that in subjects seronegative for

SARS-CoV-2 at baseline.

The safety, reactogenicity, and immunogenicity of a booster dose of Spikevax (original) wereevaluated in a Phase 2, randomised, observer-blind, placebo-controlled, dose-confirmation study inparticipants 18 years of age and older (NCT04405076). In this study, 198 participants received twodoses (0.5 mL, 100 micrograms 1 month apart) of the Spikevax (original) vaccine primary series. In anopen-label phase of this study, 167 of those participants received a single booster dose (0.25 mL,50 micrograms) at least 6 months after receiving the second dose of the primary series. The solicitedadverse reaction profile for the booster dose (0.25 mL, 50 micrograms) was similar to that after thesecond dose in the primary series.

The safety, reactogenicity, and immunogenicity of a booster dose of Spikevax bivalent

Original/Omicron BA.1 were evaluated in a Phase 2/3 open-label study in participants 18 years of ageand older (mRNA-1273-P205). In this study, 437 participants received the Spikevax bivalent

Original/Omicron BA.1 50 microgram booster dose, and 377 participants received the Spikevax(original) 50 microgram booster dose.

Spikevax bivalent Original/Omicron BA.1 had a reactogenicity profile similar to that of the Spikevax(original) booster given as a second booster dose. The frequency of adverse reactions afterimmunisation with Spikevax bivalent Original/Omicron BA.1 was also similar or lower relative to thatof a first booster dose of Spikevax (original) (50 micrograms) and relative to the second dose of the

Spikevax (original) primary series (100 micrograms). The safety profile of Spikevax bivalent

Original/Omicron BA.1 (median follow-up period of 113 days) was similar to the safety profile of

Spikevax (original) (median follow-up period of 127 days).

Spikevax bivalent Original/Omicron BA.4-5 (booster dose)

The safety, reactogenicity, and immunogenicity of a bivalent booster dose of Spikevax bivalent

Original/Omicron BA.4-5 were evaluated in a Phase 2/3 open-label study in participants 18 years ofage and older (mRNA-1273-P205). In this study, 511 participants received a booster dose of Spikevaxbivalent Original/Omicron BA.4-5 (50 micrograms), and 376 participants received a booster dose of

Spikevax (original) (50 micrograms).

Spikevax bivalent Original/Omicron BA.4-5 had a reactogenicity profile similar to that of the

Spikevax (original) booster given as a second booster dose.

Spikevax XBB.1.5 (booster dose)

The safety, reactogenicity and immunogenicity of a booster dose of Spikevax XBB.1.5 were evaluatedin a Phase 2/3 open-label study in adults (mRNA-1273-P205, Part J). In this study, 50 participantsreceived a booster dose of Spikevax XBB.1.5 (50 micrograms) and 51 participants received a boosterdose of an investigational bivalent Omicron XBB.1.5/BA.4-5 vaccine (50 micrograms).

The reactogenicity profile of Spikevax XBB.1.5 was similar to that of Spikevax (original) and

Spikevax bivalent Original/Omicron BA.4-5. The median follow-up time for both vaccine groups inthis interim analysis was 20 days (range of 20 to 22 days with data cut-off date of 16 May 2023).

Spikevax (original) in solid organ transplant recipients

The safety, reactogenicity, and immunogenicity of Spikevax (original) were evaluated in a two-part

Phase 3b open-label study in adult solid organ transplant (SOT) recipients, including kidney and livertransplants (mRNA-1273-P304). A 100 microgram (0.5 mL) dose was administered, which was thedose authorised at the time of study conduct.

In Part A, 128 SOT recipients received a third dose of Spikevax (original). In Part B, 159 SOTrecipients received a booster dose at least 4 months after the last dose (fourth dose for mRNA vaccinesand third dose for non-mRNA vaccines).

Reactogenicity was consistent with the known profile of Spikevax (original). There were nounexpected safety findings.

The increased risk of myocarditis after vaccination with Spikevax (original) is highest in youngermales (see section 4.4).

Two large European pharmacoepidemiological studies have estimated the excess risk in youngermales following the second dose of Spikevax (original). One study showed that in a period of 7 daysafter the second dose, there were about 1.316 (95% CI: 1.299, 1.333) extra cases of myocarditis in 12to 29 year-old males per 10 000 compared to unexposed persons. In another study, in a period of28 days after the second dose, there were 1.88 (95% CI: 0.956, 2.804) extra cases of myocarditis in 16to 24 year-old males per 10 000 compared to unexposed persons.

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 and include batch/Lot number if available.

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

Pharmacotherapeutic group: Vaccines, COVID-19 vaccines, ATC code: J07BN01

Elasomeran and its variant strains contain mRNA encapsulated in lipid nanoparticles. The mRNAencodes for the full-length SARS-CoV-2 spike protein modified with 2 proline substitutions within theheptad repeat 1 domain (S-2P) to stabilise the spike protein into a prefusion conformation. Afterintramuscular injection, cells at the injection site and the draining lymph nodes take up the lipidnanoparticle, effectively delivering the mRNA sequence into cells for translation into viral protein.

The delivered mRNA does not enter the cellular nucleus or interact with the genome, isnon-replicating, and is expressed transiently mainly by dendritic cells and subcapsular sinusmacrophages. The expressed, membrane-bound spike protein of SARS-CoV-2 is then recognised byimmune cells as a foreign antigen. This elicits both T-cell and B-cell responses to generate neutralisingantibodies against the spike protein, which may contribute to protection against COVID-19.

Immunogenicity in adults - after Spikevax XBB.1.5 dose (0.5 mL, 50 micrograms) versus aninvestigational bivalent XBB.1.5/BA.4-5 dose (0.5 mL, 25 micrograms/25 micrograms)

The safety, reactogenicity and immunogenicity of Spikevax XBB.1.5 50 micrograms and of a bivalentvaccine that contains equal mRNA amounts of Omicron XBB.1.5 and Omicron BA.4-5 spike proteins(25 micrograms XBB.1.5/25 micrograms BA.4-5) were evaluated in a Phase 2/3 open-label study inadults. In this study, 50 participants received Spikevax XBB.1.5 and 51 participants received theinvestigational bivalent XBB.1.5/BA.4-5 (mRNA-1273- P205, Part J). The two groups wererandomised 1:1.

The vaccines were administered as a fifth dose to adults who previously received a two-dose primaryseries of any mRNA COVID-19 vaccine, a booster dose of any mRNA COVID-19 vaccine, and abooster dose of any mRNA bivalent Original/Omicron BA.4-5 vaccine.

Spikevax XBB.1.5 and bivalent XBB.1.5/BA.4-5 elicited potent neutralising responses at Day 15against XBB.1.5, XBB.1.16, BA.4-5, BQ.1.1 and D614G. In the per-protocol immunogenicity set thatincludes all participants, with and without prior SARS-CoV-2 infection (N=49 and N=50 for Spikevax

XBB.1.5 and bivalent XBB.1.5/BA.4-5 groups, respectively), the Day 15 GMFR (95% CI) for

Spikevax XBB.1.5 and bivalent XBB.1.5/BA.4-5 was 16.7 (12.8, 21.7) and 11.6 (8.7, 15.4),respectively, against XBB.1.5 and 6.3 (4.8, 8.2) and 5.3 (3.9, 7.1) against BA.4-5.

For variants not contained in the vaccines, the Day 15 GMFR (95% CI) for Spikevax XBB.1.5 andbivalent XBB.1.5/BA.4-5 was 11.4 (8.5, 15.4) and 9.3 (7.0, 12.3) against XBB.1.16; 5.8 (4.7, 7.3) and6.1 (4.6, 7.9) against BQ.1.1 and 2.8 (2.2, 3.5) and 2.3 (1.9, 2.8) against D614G.

Immunogenicity in participants 18 years of age and older - after Spikevax bivalent Original/Omicron

BA.4-5 booster dose (0.5 mL, 25 micrograms/25 micrograms)

The safety, reactogenicity, and immunogenicity of a Spikevax bivalent Original/Omicron BA.4-5booster dose were evaluated in a Phase 2/3 open-label study in participants 18 years of age and older(mRNA-1273-P205). In this study, 511 participants received the Spikevax bivalent Original/Omicron

BA.4-5 50 microgram booster dose, and 376 participants received the Spikevax (original) 50microgram booster dose.

Study P205 Part H evaluated the safety, reactogenicity and immunogenicity of Spikevax bivalent

Original/Omicron BA.4-5 when administered as a second booster dose to adults who previouslyreceived 2 doses of Spikevax (original) (100 microgram) as a primary series and a first booster dose of

Spikevax (original) (50 micrograms). In P205 Part F, study participants received Spikevax (original)(50 micrograms) as a second booster dose and the Part F group serves as a within-study,non-contemporaneous comparator group to the Spikevax bivalent Original/Omicron BA.4-5 group.

In this study, the primary immunogenicity analysis was based on the primary immunogenicity setwhich includes participants with no evidence of SARS-CoV-2 infection at baseline (pre-booster). Inthe primary analysis, the observed geometric mean titre (GMT) (95% CI) at pre-booster was 87.9(72.2, 107.1) and increased to 2 324.6 (1 921.2, 2 812.7) 28 days after the Spikevax bivalent

Original/Omicron BA.4-5 booster dose. The Day 29 GMR for Spikevax Original/Omicron BA.4-550 microgram booster dose versus the Spikevax (original) 50 microgram booster dose was 6.29 (5.27,7.51), meeting the pre-specified criterion for superiority (lower bound of CI >1).

The estimated neutralising antibody GMTs (95% CI) against Omicron BA.4/BA.5 adjusted forpre-booster titre and age group were 2 747.3 (2 399.2, 3 145.9) and 436.7 (389.1, 490.0) 28 days after

Spikevax bivalent Original/Omicron BA.4-5 and Spikevax (original) booster doses, respectively, andthe GMR (95% CI) was 6.29 (5.27, 7.51), meeting the pre-specified criterion for non-inferiority (lowerbound of CI >0.667).

Immunogenicity in adults - after Spikevax bivalent Original/Omicron BA.1 booster dose (0.5 mL,25 micrograms/25 micrograms)

The safety, reactogenicity, and immunogenicity of a Spikevax bivalent Original/Omicron BA.1booster dose were evaluated in a Phase 2/3 open-label study in participants 18 years of age and older(mRNA-1273-P205). In this study, 437 participants received the Spikevax bivalent Original/Omicron

BA.1 50 microgram booster dose, and 377 participants received the Spikevax (original) 50 microgrambooster dose.

Study P205 Part G evaluated the safety, reactogenicity and immunogenicity of Spikevax bivalent

Original/Omicron BA.1 when administered as a second booster dose to adults who previously received2 doses of Spikevax (original) (100 microgram) as a primary series and a booster dose of Spikevax(original) (50 micrograms) at least 3 months prior to enrolment. In P205 Part F, study participantsreceived Spikevax (original) (50 micrograms) as a second booster dose and the Part G group serves asa within-study, non-contemporaneous comparator group to the Spikevax bivalent Original/Omicron

BA.1 group.

In this study, the primary immunogenicity analysis was based on the primary immunogenicity setwhich includes participants with no evidence of SARS-CoV-2 infection at baseline (pre-booster). Inthe primary analysis, the original SARS-CoV-2 estimated neutralising antibody geometric mean titre(GMT) and corresponding 95% CI was 6 422.3 (5 990.1, 6 885.7) and 5 286.6 (4 887.1, 5 718.9)28 days after the Spikevax bivalent Original/Omicron BA.1 and Spikevax (original) booster doses,respectively. These GMTs represent the ratio between response of Spikevax bivalent

Original/Omicron BA.1 versus Spikevax (original) against the ancestral SARS-CoV-2 (D614G) strain.

The GMR (97.5% CI) was 1.22 (1.08, 1.37) meeting the pre-specified criterion for non-inferiority(lower bound of 97.5% CI ≥0.67).

The estimated Day 29 neutralising antibody GMTs against Omicron, BA.1 were 2 479.9 (2 264.5,2 715.8) and 1 421.2 (1 283.0, 1 574.4) in the Spikevax bivalent Original/Omicron BA.1 and Spikevax(original) booster groups, respectively, and the GMR (97.5% CI) was 1.75 (1.49, 2.04), which met thepre-specified superiority criterion (lower bound of CI >1).

Three-month antibody persistence of Spikevax bivalent Original/Omicron BA.1 booster vaccineagainst COVID-19

Participants in Study P205 Part G were sequentially enrolled to receive 50 micrograms of Spikevax(original) (n = 376) or Spikevax bivalent Original/Omicron BA.1 (n = 437) as second booster doses. Inparticipants with no pre-booster incidence of SARS-CoV-2, Spikevax bivalent Original/Omicron BA.1elicited Omicron-BA.1-neutralising antibody titres (observed GMT) that were significantly higher(964.4 [834.4, 1 114.7]) than those of Spikevax (original) (624.2 [533.1, 730.9]) and similar betweenboosters against ancestral SARS-CoV-2 at three months.

The adult study was a randomised, placebo-controlled, observer-blind Phase 3 clinical study(NCT04470427) that excluded individuals who were immunocompromised or had receivedimmunosuppressants within 6 months, as well as participants who were pregnant, or with a knownhistory of SARS-CoV-2 infection. Participants with stable HIV disease were not excluded. Influenzavaccines could be administered 14 days before or 14 days after any dose of Spikevax (original).

Participants were also required to observe a minimum interval of 3 months after receipt ofblood/plasma products or immunoglobulins prior to the study in order to receive either placebo or

Spikevax (original).

A total of 30 351 subjects were followed for a median of 92 days (range: 1-122) for the developmentof COVID-19 disease.

The primary efficacy analysis population (referred to as the Per Protocol Set or PPS), included28 207 subjects who received either Spikevax (original) (n=14 134) or placebo (n=14 073) and had anegative baseline SARS-CoV-2 status. The PPS study population included 47.4% female, 52.6% male,79.5% White, 9.7% African American, pct. 4.6% Asian, and 6.2% other. 19.7% of participants identifiedas Hispanic or Latino. The median age of subjects was 53 years (range 18-94). A dosing window of -7to +14 days for administration of the second dose (scheduled at day 29) was allowed for inclusion inthe PPS. 98% of vaccine recipients received the second dose 25 days to 35 days after dose 1(corresponding to -3 to +7 days around the interval of 28 days).

COVID-19 cases were confirmed by Reverse Transcriptase Polymerase Chain Reaction (RT PCR) andby a Clinical Adjudication Committee. Vaccine efficacy overall and by key age groups are presentedin Table 5.

Table 5. Vaccine efficacy analysis: confirmed COVID-19# regardless of severity starting 14 daysafter the 2nd dose - PPS

Spikevax (original) Placebo

Age group COVID- Incidence rate Incidence rate(years) Subjects 19 cases of COVID-19 Subjects COVID- of COVID-19 % Vaccine

N per 1 000 N 19 casesn n per 1 000 efficacy (95%person-years person-years CI)*

Overall( 18) 14 134 11 3.328 14 073 185 56.510 94.1≥ (89.3, 96.8)**18 to <65 10 551 7 2.875 10 521 156 64.625 95.6(90.6, 97.9)≥65 3 583 4 4.595 3 552 29 33.728 86.4(61.4, 95.2)≥65 to <75 2 953 4 5.586 2 864 22 31.744 82.4%(48.9, 93.9)≥75 630 0 0 688 7 41.968 100%(NE, 100)#COVID-19: symptomatic COVID-19 requiring positive RT-PCR result and at least 2 systemic symptoms or1 respiratory symptom. Cases starting 14 days after the 2nd dose.

*Vaccine efficacy and 95% confidence interval (CI) from the stratified Cox proportional hazard model

** CI not adjusted for multiplicity. Multiplicity adjusted statistical analyses were carried out in an interimanalysis based on less COVID-19 cases, not reported here.

Among all subjects in the PPS, no cases of severe COVID-19 were reported in the vaccine groupcompared with 30 of 185 (16%) cases reported in the placebo group. Of the 30 participants with severedisease, 9 were hospitalised, 2 of which were admitted to an intensive care unit. The majority of theremaining severe cases fulfilled only the oxygen saturation (SpO2) criterion for severe disease (≤ 93%on room air).

The vaccine efficacy of Spikevax (original) to prevent COVID-19, regardless of prior SARS-CoV-2infection (determined by baseline serology and nasopharyngeal swab sample testing) from 14 daysafter Dose 2 was 93.6% (95% CI: 88.6, 96.5).

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.

Immunogenicity in adults - after booster dose (0.25 mL, 50 micrograms)

The safety, reactogenicity, and immunogenicity of a booster dose of Spikevax (original) wereevaluated in a Phase 2, randomised, observer-blind, placebo-controlled, dose-confirmation study inparticipants 18 years of age and older (NCT04405076). In this study, 198 participants received twodoses (0.5 mL, 100 micrograms 1 month apart) of the Spikevax (original) vaccine as primary series. Inan open-label phase, 149 of those participants (Per Protocol Set) received a single booster dose(0.25 mL, 50 micrograms) at least 6 months after receiving the second dose in the primary series. Asingle booster dose (0.25 mL, 50 micrograms) was shown to result in a geometric mean fold rise(GMFR) of 12.99 (95% CI: 11.04, 15.29) in neutralising antibodies from pre-booster compared to28 days after the booster dose. The GMFR in neutralising antibodies was 1.53 (95% CI: 1.32, 1.77)when compared 28 days post dose 2 (primary series) to 28 days after the booster dose.

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

Safety and immunogenicity of a heterologous booster with Spikevax (original) were studied in aninvestigator-initiated study with 154 participants. The minimum time interval between primary seriesusing a vector-based or RNA-based COVID-19 vaccine and booster injection with Spikevax (original)was 12 weeks (range: 12 weeks to 20.9 weeks). The dose used for boosting in this study was100 micrograms. Neutralising antibody titres as measured by a pseudovirus neutralisation assay wereassessed on Day 1 prior to administration and at Day 15 and Day 29 after the booster dose. A boosterresponse was demonstrated regardless of primary vaccination.

Only short-term immunogenicity data are available; long-term protection and immunological memoryare currently unknown.

COV-BOOST was a multicentre, randomised Phase 2 investigator-initiated study of third dose boostervaccination against COVID-19 with a subgroup to investigate detailed immunology. Participants wereadults aged 30 years or older, in good physical health (mild to moderate well-controlled co-morbiditieswere permitted), who had received two doses of either Pfizer-BioNTech or Oxford-AstraZeneca (firstdose in December 2020, January 2021 or February 2021), and were at least 84 days post second doseby the time of enrolment. Spikevax (original) boosted antibody and neutralising responses and waswell tolerated regardless of the prime series. The dose used for boosting in this study was100 micrograms. Neutralising antibody titres as measured by a pseudovirus neutralisation assay wereassessed on Day 28 after the booster dose.

The adolescent study was a Phase 2/3 randomised, placebo-controlled, observer-blind clinical study(NCT04649151) to evaluate the safety, reactogenicity, and efficacy of Spikevax (original) inadolescents 12 to 17 years of age. Participants with a known history of SARS-CoV-2 infection wereexcluded from the study. A total of 3 732 participants were randomised 2:1 to receive 2 doses of

Spikevax (original) or saline placebo 1 month apart.

A secondary efficacy analysis was performed in 3 181 participants who received 2 doses of either

Spikevax (original) (n=2 139) or placebo (n=1 042) and had a negative baseline SARS-CoV-2 statusin the Per Protocol Set. Between participants who received Spikevax (original) and those who receivedplacebo, there were no notable differences in demographics or pre-existing medical conditions.

COVID-19 was defined as symptomatic COVID-19 requiring positive RT-PCR result and at least2 systemic symptoms or 1 respiratory symptom. Cases starting 14 days after the second dose.

There were zero symptomatic COVID-19 cases in the Spikevax (original) group and 4 symptomatic

COVID-19 cases in the placebo group.

Immunogenicity in adolescents 12 to 17 years of age - after Spikevax primary vaccination

A non-inferiority analysis evaluating SARS-CoV-2 50% neutralising titres and seroresponse rates28 days after Dose 2 was conducted in the per-protocol immunogenicity subsets of adolescents aged12 through 17 (n=340) in the adolescent study and in participants aged 18 through 25 (n=296) in theadult study. Subjects had no immunologic or virologic evidence of prior SARS-CoV-2 infection atbaseline. The geometric mean ratio (GMR) of the neutralising antibody titres in adolescents 12 to17 years of age compared to the 18- to 25-year-olds was 1.08 (95% CI: 0.94, 1.24). The difference inseroresponse rate was 0.2% (95% CI: -1.8, 2.4). Non-inferiority criteria (lower bound of the 95% CIfor GMR > 0.67 and lower bound of the 95% CI of the seroresponse rate difference > -10%) were met.

Immunogenicity in adolescents 12 years through 17 years of age - after Spikevax (original) boosterdose

The primary immunogenicity objective of the booster phase of this study was to inferefficacy of the booster dose in participants 12 years through 17 years of age by comparingpost-booster immune responses (Day 29) to those obtained post-dose 2 of the primary series (Day 57)in young adults (18 to 25 years of age) in the adult study. Efficacy of the 50 microgram Spikevaxbooster dose was inferred if post-booster dose immune responses (nAb geometric mean concentration[GMC] and seroresponse rate [SRR]) meet prespecified noninferiority criteria (for both GMC and

SRR) compared to those measured following completion of the 100 microgram Spikevax primaryseries among a subset of young adults (18 to 25 years) in the pivotal adult efficacy study.

In an open-label phase of this study, participants 12 years through 17 years of age received a singlebooster dose at least 5 months after completion of the primary series (two doses 1 month apart). Theprimary immunogenicity analysis population included 257 booster dose participants in this study and arandom subset of 295 participants from the young adult study (ages ≥18 to ≤25 years) who previouslycompleted a primary vaccination series of two doses 1 month apart of Spikevax. Both groups ofparticipants included in the analysis population had no serologic or virologic evidence of

SARS-CoV-2 infection prior to the first primary series dose and prior to the booster dose, respectively.

The GMR of the adolescent booster dose Day 29 GMC compared with young adults: Day 57 GMRwas 5.1 (95% CI: 4.5, 5.8), meeting the noninferiority criteria (i.e., lower bound of the 95% CI >0.667(1/1.5); point estimate ≥0.8); the SRR difference was 0.7% (95% CI: -0.8, 2.4), meeting thenoninferiority criteria (lower bound of the 95% of the SRR difference >-10%).

In the 257 participants, pre-booster (booster dose-Day 1) nAb GMC was 400.4 (95% CI: 370.0,433.4); on BD-Day 29, the GMC was 7 172.0 (95% CI: 6 610.4, 7 781.4). Post-booster boosterdose-Day 29 GMC increased approximately 18-fold from pre-booster GMC, demonstrating thepotency of the booster dose to adolescents. The SRR was 100 (95% CI: 98.6, 100.0).

The prespecified success criteria for the primary immunogenicity objective were met, thusenabling the inference of vaccine efficacy from the adult study.

Clinical efficacy in children 6 years through 11 years of age

The paediatric study was a Phase 2/3 randomised, placebo-controlled, observer-blind, clinical study toevaluate the safety, reactogenicity, and efficacy of Spikevax (original) in children aged 6 yearsthrough 11 years in the United States and Canada (NCT04796896). Participants with a known historyof SARS-CoV-2 infection were excluded from the study. A total of 4 016 participants wererandomised 3:1 to receive 2 doses of Spikevax (original) or saline placebo 1 month apart.

A secondary efficacy analysis evaluating confirmed COVID-19 cases accrued up to the data cutoffdate of 10 November 2021 was performed in 3 497 participants who received two doses (0.25 mL at 0and 1 month) of either Spikevax (original) (n=2 644) or placebo (n=853) and had a negative baseline

SARS-CoV-2 status in the Per Protocol Set. Between participants who received Spikevax (original)and those who received placebo, there were no notable differences in demographics.

COVID-19 was defined as symptomatic COVID-19 requiring positive RT-PCR result and at least2 systemic symptoms or 1 respiratory symptom. Cases starting 14 days after the second dose.

There were three COVID-19 cases (0.1%) in the Spikevax (original) group and four COVID-19 cases(0.5%) in the placebo group.

Immunogenicity in children 6 years through 11 years of age

An analysis evaluating SARS-CoV-2 50% neutralising titres and seroresponse rates 28 days after

Dose 2 was conducted in a subset of children aged 6 years through 11 years (n=319) in the paediatricstudy and in participants aged 18 through 25 years (n=295) in the adult study. Subjects had noimmunologic or virologic evidence of prior SARS-CoV-2 infection at baseline. The GMR of theneutralising antibody titres in children 6 years through 11 years of age compared to the 18- to 25-year-olds was 1.239 (95% CI: 1.072, 1.432). The difference in seroresponse rate was 0.1% (95% CI: -1.9,2.1). Non-inferiority criteria (lower bound of the 95% CI for GMR > 0.67 and lower bound of the95% CI of the seroresponse rate difference > -10%) were met.

Immunogenicity in children 6 years through 11 years of age - after Spikevax (original) booster dose

The primary immunogenicity objective of the booster phase of this study was to infer efficacy of thebooster dose in participants 6 years through 11 years of age by comparing post-booster dose immuneresponses (Day 29) to those obtained post dose 2 of the primary series (Day 57) in young adults (18 to25 years of age) in that study, where 93% efficacy was demonstrated. Efficacy of the 25 microgram

Spikevax booster dose was inferred if post-booster dose immune responses (neutralising antibody[nAb] geometric mean concentration [GMC] and seroresponse rate [SRR]) meet pre-specified non-inferiority criteria (for both GMC and SRR) compared to those measured following completion of the100 microgram Spikevax primary series among a subset of young adults (18 to 25 years) in the pivotaladult efficacy trial.

In an open-label phase of this study, participants 6 years through 11 years of age received a singlebooster dose at least 6 months after completion of the primary series (two doses 1 month apart). Theprimary immunogenicity analysis population included 95 booster dose participants in 6 years through11 years and a random subset of 295 participants from the young adult study who received two doses1 month apart of Spikevax. Both groups of participants included in the analysis population had noserologic or virologic evidence of SARS-CoV-2 infection prior to the first primary series dose andprior to the booster dose, respectively.

In the 95 participants, on booster dose-Day 29, the GMC was 5 847.5 (95% CI: 4 999.6, 6 839.1). The

SRR was 100 (95% CI: 95.9, 100.0). Serum nAb levels for children 6 years through 11 years in theper-protocol immunogenicity subset with pre-booster SARS-CoV-2 negative status and thecomparison with those from young adults (18 to 25 years of age) were studied. The GMR of boosterdose Day 29 GMC compared to young adults Day 57 GMC was 4.2 (95% CI: 3.5, 5.0), meeting thenoninferiority criteria (i.e., lower bound of the 95% CI > 0.667); the SRR difference was 0.7%(95% CI: -3.5, 2.4), meeting the noninferiority criteria (lower bound of the 95% of the SRR difference>-10%).

The prespecified success criteria for the primary immunogenicity objective were met, thus enablingthe inference of booster dose vaccine efficacy. The brisk recall response evident within 4 weeks ofbooster dosing is evidence of the robust priming induced by the Spikevax primary series.

A Phase 2/3 study was conducted to evaluate the safety, tolerability, reactogenicity, and efficacy of

Spikevax in healthy children 6 months through 11 years of age. The study enrolled children in 3 agegroups: 6 years through 11 years; 2 years through 5 years; and 6 months through 23 months.

A descriptive efficacy analysis evaluating confirmed COVID-19 cases accrued up to the data cutoffdate of 21 February 2022 was performed in 5 476 participants 6 months through 5 years of age whoreceived two doses (at 0 and 1 month) of either Spikevax (n=4 105) or placebo (n=1 371) and had anegative baseline SARS-CoV-2 status (referred to as the Per Protocol Set for Efficacy). Betweenparticipants who received Spikevax and those who received placebo, there were no notable differencesin demographics.

The median length of follow-up for efficacy post-Dose 2 was 71 days for participants 2 years through5 years of age and 68 days for participants 6 months through 23 months of age.

Vaccine efficacy in this study was observed during the period when the B.1.1.529 (Omicron) variantwas the predominant variant in circulation.

Vaccine efficacy (VE) in Part 2 for the Per Protocol Set for Efficacy for COVID-19 cases 14 days ormore after dose 2 using the “COVID-19 P301 case definition” (i.e., the definition employed in thepivotal adult efficacy study) was 46.4% (95% CI: 19.8, 63.8) for children 2 years through 5 years ofage and 31.5% (95% CI: -27.7, 62.0) for children 6 months through 23 months of age.

For children aged 2 years through 5 years of age, comparison of Day 57 nAb responses in this Part 2per-protocol immunogenicity subset (n = 264; 25 micrograms) to those of young adults (n = 295;100 micrograms) demonstrated a GMR of 1.014 (95% CI: 0.881, 1.167), meeting the noninferioritysuccess criteria (i.e., lower bound of the 95% CI for GMR ≥ 0.67; point estimate ≥ 0.8). The geometricmean fold rise (GMFR) from baseline to Day 57 for these children was 183.3 (95% CI: 164.03,204.91). The difference in seroresponse rates (SRR) between the children and young adults was -0.4%(95% CI: -2.7%, 1.5%), also meeting the noninferiority success criteria (lower bound of the 95% CI ofthe SRR difference > -10%).

For infants and toddlers from 6 months through 23 months of age, comparison of Day 57 nAbresponses in this Part 2 per-protocol immunogenicity subset (n = 230; 25 micrograms) to those ofyoung adults (n = 295; 100 micrograms) demonstrated a GMR of 1.280 (95% CI: 1.115, 1.470),meeting the noninferiority success criteria (i.e., lower bound of the 95% CI for GMR ≥ 0.67; pointestimate ≥ 0.8). The difference in SRR rates between the infants/toddlers and young adults was 0.7%(95% CI: -1.0%, 2.5%), also meeting the noninferiority success criteria (lower bound of the 95% CI ofthe seroresponse rate difference > -10%).

Accordingly, the prespecified success criteria for the primary immunogenicity objective were met forboth age groups, allowing efficacy of 25 micrograms to be inferred in both children 2 years through5 years and infants and toddlers aged 6 months through 23 months (Tables 6 and 7).

Table 6. Summary of geometric mean concentration ratio and seroresponse rate - comparison ofindividuals 6 months through 23 months of age to participants 18 years through 25 years of age- per-protocol immunogenicity set6 months through 18 years through 6 months through 23 months/23 months 25 years 18 years through 25 yearsn=230 n=291

Assay Time GMC GMC GMC ratio Metpoint (95% CI)* (95% CI)* (95% CI)a noninferiorityobjective(Y/N)b1 780.7 1 390.8 1.3(1 606.4, 1 973.8) (1 269.1, 1 524.2) (1.1, 1.5)

SARS-CoV-2 28 days Difference inneutralisation after Seroresponse Seroresponse seroresponse Yassayc Dose 2 % % rate %(95% CI)d (95% CI)d (95% CI)e100 99.3 0.7(98.4, 100) (97.5, 99.9) (-1.0, 2.5)

GMC = Geometric mean concentrationn = number of participants with non-missing data at baseline and at Day 57

* Antibody values reported as below the lower limit of quantification (LLOQ) are replaced by 0.5 x

LLOQ. Values greater than the upper limit of quantification (ULOQ) are replaced by the ULOQ ifactual values are not available.

a The log-transformed antibody levels are analysed using an analysis of covariance (ANCOVA) modelwith the group variable (participants 6 months through 5 years of age and young adults) as fixed effect.

The resulted LS means, difference of LS means, and 95% CI are back transformed to the original scalefor presentation.

b Noninferiority is declared if the lower bound of the 2-sided 95% CI for the GMC ratio is greater than0.67, with a point estimate of >0.8 and the lower bound of the 2-sided 95% CI for difference inseroresponse rate is greater than -10%, with a point estimate of >-5%.

c Final geometric mean antibody concentrations (GMC) in AU/mL were determined using SARS-CoV-2microneutralisation assay.

d Seroresponse due to vaccination specific to SARS-CoV-2 RVP neutralising antibody concentration at asubject level is defined in protocol as a change from below LLOQ to equal or above 4 x LLOQ, or atleast a 4-fold rise if baseline is equal to or above LLOQ. Seroresponse 95% CI is calculated using the

Clopper-Pearson method.

e Difference in seroresponse rate 95% CI is calculated using the Miettinen-Nurminen (score) confidence limits.

Table 7. Summary of geometric mean concentration ratio and seroresponse rate - comparison ofindividuals 2 years through 5 years of age to participants 18 years through 25 years of age -per-protocol immunogenicity set2 years through 18 years through 2 years through 5 years/5 years 25 years 18 years through 25 yearsn=264 n=291

Assay Time GMC GMC GMC Ratio Met

Point (95% CI)* (95% CI)* (95% CI)a noninferiorityobjective(Y/N)b1 410.0 1 390.8 1.0(1 273.8, 1 560.8) (1 262.5, 1 532.1) (0.9, 1.2)

SARS-CoV-2 28 days Difference inneutralisation after Seroresponse Seroresponse seroresponse Yassayc Dose 2 % % rate %(95% CI)d (95% CI)d (95% CI)e98.9 99.3 -0.4(96.7, 99.8) (97.5, 99.9) (-2.7, 1.5)

GMC = Geometric mean concentrationn = number of participants with non-missing data at baseline and at Day 57

* Antibody values reported as below the lower limit of quantification (LLOQ) are replaced by 0.5 x

LLOQ. Values greater than the upper limit of quantification (ULOQ) are replaced by the ULOQ ifactual values are not available.

a The log-transformed antibody levels are analysed using an analysis of covariance (ANCOVA) modelwith the group variable (participants 6 months through 5 years of age and young adults) as fixed effect.

The resulted LS means, difference of LS means, and 95% CI are back transformed to the original scalefor presentation.

b Noninferiority is declared if the lower bound of the 2-sided 95% CI for the GMC ratio is greater than0.67, with a point estimate of >0.8 and the lower bound of the 2-sided 95% CI for difference inseroresponse rate is greater than -10%, with a point estimate of >-5%.

c Final geometric mean antibody concentrations (GMC) in AU/mL were determined using SARS-CoV-2microneutralisation assay.

d Seroresponse due to vaccination specific to SARS-CoV-2 RVP neutralizing antibody concentration at asubject level is defined in protocol as a change from below LLOQ to equal or above 4 x LLOQ, or atleast a 4-fold rise if baseline is equal to or above LLOQ. Seroresponse 95% CI is calculated using the

Clopper-Pearson method.

e Difference in seroresponse rate 95% CI is calculated using the Miettinen-Nurminen (score) confidence limits.

Available data in children 12 weeks to 6 months of age

The safety and immunogenicity of Spikevax bivalent Original/Omicron BA.1 were evaluated inchildren 12 weeks to 6 months of age in Study P206. During the dose-finding part of the study, twodose levels (5 mcg and 10 mcg) evaluated as a two-dose regimen were generally well tolerated but didnot lead to a substantial immune response.

Immunogenicity in solid organ transplant recipients

The safety, reactogenicity, and immunogenicity of Spikevax (original) were evaluated in a two-part

Phase 3b open-label study in adult solid organ transplant (SOT) recipients, including kidney and livertransplants (mRNA-1273-P304). A 100 microgram (0.5 mL) dose was administered, which was thedose authorised at the time of study conduct.

In Part A, 128 SOT recipients received a third dose of Spikevax (original). In Part B, 159 SOTrecipients received a booster dose at least 4 months after the last dose.

Immunogenicity in the study was assessed by measurement of neutralising antibodies againstpseudovirus expressing the ancestral SARS-CoV-2 (D614G) strain at 1 month after Dose 2, Dose 3,booster dose and up to 12 months from the last dose in Part A, and up to 6 months from booster dosein Part B.

Three doses of Spikevax (original) induced enhanced neutralising antibody titres compared topre-dose 1 and post-dose 2. A higher proportion of SOT participants who had received three dosesachieved seroresponse compared to participants who had received two doses. The neutralisingantibody levels observed in SOT liver participants who had received three doses was comparable tothe post-dose 2 responses observed in the immunocompetent, baseline SARS-CoV-2-negative adultparticipants. The neutralising antibody responses continued to be numerically lower post-dose 3 in

SOT kidney participants compared to SOT liver participants. The neutralising levels observed onemonth after Dose 3 persisted through six months with antibody levels maintained at 26-fold higher andseroresponse rate at 67% compared to baseline.

A fourth (booster) dose of Spikevax (original) enhanced neutralising antibody response in

SOT participants compared to post-dose 3, regardless of the previous vaccines received [mRNA-1273(Moderna), BNT162b2 or any mRNA-containing combination]; however, SOT kidney participantshad numerically lower neutralising antibody responses compared to SOT liver participants.

Spikevax (original) was assessed in individuals 6 months of age and older, including 3 768 subjects65 years of age and older. The efficacy of Spikevax (original) was consistent between elderly(≥65 years) and younger adult subjects (18-64 years).

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

Spikevax (original) in one or more subsets of the paediatric population in the prevention of COVID-19(see section 4.2 for information on paediatric use).

Not applicable.

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

General toxicity studies were conducted in rats (intramuscularly receiving up to 4 doses exceeding thehuman dose once every 2 weeks). Transient and reversible injection site oedema and erythema andtransient and reversible changes in laboratory tests (including increases in eosinophils, activatedpartial thromboplastin time, and fibrinogen) were observed. Results suggests the toxicity potential tohumans is low.

In vitro and in vivo genotoxicity studies were conducted with the novel lipid component SM-102 ofthe vaccine. Results suggests the genotoxicity potential to humans is very low. Carcinogenicity studieswere not performed.

In a developmental toxicity study, 0.2 mL of a vaccine formulation containing the same quantity ofmRNA (100 micrograms) and other ingredients included in a single human dose of Spikevax (original)was administered to female rats by the intramuscular route on four occasions: 28 and 14 days prior tomating, and on gestation days 1 and 13. SARS-CoV-2 antibody responses were present in maternalanimals from prior to mating to the end of the study on lactation day 21 as well as in foetuses andoffspring. There were no vaccine-related adverse effects on female fertility, pregnancy, embryofoetal or offspring development or postnatal development. No data are available of Spikevax (original)vaccine placental transfer or excretion in milk.

SM-102 (heptadecan-9-yl 8-{(2-hydroxyethyl)[6-oxo-6-(undecyloxy)hexyl]amino}octanoate)

Cholesterol1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)1,2-Dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG2000-DMG)

Trometamol

Trometamol hydrochloride

Acetic acid

Sodium acetate trihydrate

Sucrose

Water for injections

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

Unopened multidose vial (Spikevax LP.8.1 0.1 mg/mL dispersion for injection)9 months at -50ºC to -15ºC.

Within the period of 9 months, after removal from the freezer, the unopened vaccine vial may bestored refrigerated at 2°C to 8°C, protected from light, for a maximum of 30 days.

Chemical and physical stability has also been demonstrated for unopened vaccine vials when storedfor 12 months at -50°C to -15°C provided that once thawed and stored at 2°C to 8°C, protectedfrom light, the unopened vial will be used up within a maximum of 14 days (instead of 30 days,when stored at -50ºC to -15ºC for 9 months), but not exceeding a total storage time of 12 months.

* Upon moving the vaccine to 2°C to 8°C storage, the outer carton should be marked with the newdiscard date at 2°C to 8°C.

* 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 marked with the new discard date at 2°C to 8°C.

Within this period, up to 36 hours may be used for transportation at 2°C to 8°C (see section 6.4).

Once thawed, the vaccine should not be refrozen.

The unopened vaccine may be stored at 8°C to 25°C up to 24 hours after removal from refrigeratedconditions.

Punctured multidose vials (Spikevax LP.8.1 0.1 mg/mL dispersion for injection)

Chemical and physical in-use stability has been demonstrated for 19 hours at 2°C to 25ºC after initialpuncture (within the allowed use period of 30 days or 14 days, respectively, at 2°C to 8ºC andincluding 24 hours at 8°C to 25ºC). From a microbiological point of view, the product should be usedimmediately. If the vaccine is not used immediately, in-use storage times and conditions are theresponsibility of the user.

Spikevax LP.8.1 50 micrograms dispersion for injection in pre-filled syringe and Spikevax LP.8.125 micrograms dispersion for injection in pre-filled syringe9 months at -50ºC to -15ºC.

Within the period of 9 months, after removal from the freezer, pre-filled syringes may be storedrefrigerated at 2°C to 8°C, protected from light, for maximum 30 days (see section 6.4).

Chemical and physical stability has also been demonstrated for unopened pre-filled syringes whenstored for 12 months at -50°C to -15°C provided that once thawed and stored at 2°C to 8°C,protected from light, the pre-filled syringe will be used up within a maximum of 14 days (insteadof 30 days, when stored at -50ºC to -15ºC for 9 months), but not exceeding a total storage time of12 months.

* Upon moving the vaccine to 2°C to 8°C storage, the outer carton should be marked with the newdiscard date at 2°C to 8°C.

* 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 marked with the new discard date at 2°C to 8°C.

Pre-filled syringe transport duration is limited by the shipper qualification duration.

Once thawed, the vaccine should not be refrozen.

Pre-filled syringes may be stored at 8°C to 25°C up to 24 hours after removal from refrigeratedconditions.

Spikevax LP.8.1 0.1 mg/mL dispersion for injection (multidose vials)

Store in a freezer at -50ºC to -15ºC.

Once thawed, store in a refrigerator (2°C to 8°C) and do not refreeze.

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

For storage conditions after thawing, see section 6.3.

For storage conditions of the multidose vial after first opening, see section 6.3.

If transport at -50°C to -15°C is not feasible, available data support transportation of one or morethawed vials in liquid state for up to 36 hours at 2°C to 8°C (within the 30 days or 14 days shelf life,respectively, at 2°C to 8°C). Once thawed and transported in liquid state at 2°C to 8°C, vials shouldnot be refrozen and should be stored at 2°C to 8°C until use.

Spikevax LP.8.1 50 micrograms dispersion for injection in pre-filled syringe and Spikevax LP.8.125 micrograms dispersion for injection in pre-filled syringe

Store in a freezer at -50ºC to -15ºC.

Once thawed, store in a refrigerator (2°C to 8°C) and do not refreeze.

Keep the pre-filled syringe in the outer carton in order to protect from light.

For storage conditions after thawing, see section 6.3.

If transport at -50°C to -15°C is not feasible, available data support transportation of one or morethawed pre-filled syringes in liquid state at 2°C to 8°C (within the 30 days or 14 days shelf life,respectively, at 2°C to 8°C). Once thawed and transported in liquid state at 2°C to 8°C, pre-filledsyringes should not be refrozen and should be stored at 2°C to 8°C until use. Pre-filled syringetransport duration is limited by the shipper qualification duration.

Spikevax LP.8.1 0.1 mg/mL dispersion for injection (multidose vials)2.5 mL dispersion in a (type 1 glass or type 1 equivalent glass or cyclic olefin polymer with innerbarrier coating) multidose vial with a stopper (chlorobutyl rubber) and a blue flip-off plastic cap withseal (aluminium seal).

Pack size: 10 multidose vials. Each vial contains 2.5 mL.

Spikevax LP.8.1 50 micrograms dispersion for injection in pre-filled syringe and Spikevax LP.8.125 micrograms dispersion for injection in pre-filled syringe0.25 mL or 0.5 mL dispersion in a pre-filled syringe (cyclic olefin copolymer) with plunger stopper(coated bromobutyl rubber) and a tip cap (bromobutyl rubber, without needle).

The pre-filled syringe is packaged in a paper inner tray within a carton or in 1 clear blister containing1 pre-filled syringe or 5 clear blisters containing 2 pre-filled syringes in each blister.

Pack sizes:1 pre-filled syringe10 pre-filled syringes

Each pre-filled syringe contains 0.25 mL or 0.5 mL, depending on labelled syringe volume.

Not all pack sizes may be marketed.

The vaccine should be prepared and administered by a trained healthcare professional using aseptictechniques to ensure sterility of the dispersion.

Spikevax LP.8.1 0.1 mg/mL dispersion for injection (multidose vials)

The vaccine comes ready to use once thawed.

Do not shake or dilute. Swirl the vial gently after thawing and before each withdrawal.

Verify that the vial has a blue flip-off cap and the product name is Spikevax LP.8.1.

Pierce the stopper preferably at a different site each time.

An additional overfill is included in each multidose vial to ensure that 5 doses of 0.5 mL or amaximum of 10 doses of 0.25 mL can be delivered, depending on the individual’s age.

Thaw each multidose vial before use following the instructions below (Table 8).

Table 8. Thawing instructions for multidose vials before use

Thaw instructions and duration

Thaw Thaw

Configuration temperature Thaw temperature(in a duration (at room T haw durationrefrigerator) temperature)

Multidose vial 2° - 8°C 2 hours and30 minutes 15°C - 25°C 1 hour

The vaccine must be administered intramuscularly. The preferred site is the deltoid muscle of theupper arm. Do not administer this vaccine intravascularly, subcutaneously or intradermally.

Multidose vials

Spikevax LP.8.1 50 micrograms dispersion for injection in pre-filled syringe and Spikevax LP.8.125 micrograms dispersion for injection in pre-filled syringe

Do not shake or dilute the contents of the pre-filled syringe.

Each pre-filled syringe is for single use only. The vaccine comes ready to use once thawed.

One (1) dose of 0.25 mL or 0.5 mL can be administered from each pre-filled syringe, depending onlabelled syringe volume. Do not use the 0.5 mL pre-filled syringe to administer a 0.25 mL dose.

Spikevax LP.8.1 is supplied in a single-dose, pre-filled syringe (without needle) containing 0.25 mL(25 micrograms of SARS-CoV-2 LP.8.1 mRNA) or 0.5 mL (50 micrograms of SARS-CoV-2 LP.8.1mRNA) and must be thawed prior to administration.

Thaw each pre-filled syringe before use following the instructions below. Syringes may be thawed inthe blister packs (each blister containing 1 or 2 pre-filled syringes, depending on pack size) or in thecarton itself, either in the refrigerator or at room temperature (Table 9).

Table 9. Thawing instructions for Spikevax LP.8.1 pre-filled syringes and cartons before use

Thaw instructions and duration

Thaw Thaw

Configuration temperature Thaw temperature(in a duration (at room Thaw durationrefrigerator) (minutes) temperature) (minutes)(°C) (°C)

Blister or cartoncontaining 1 or 2 - 8 100 15 - 25 402 pre-filled syringes

Carton containing10 pre-filled syringes 2 - 8 160 15 - 25 80

Verify that the product name of the pre-filled syringe is Spikevax LP.8.1.

Handling instructions for the Spikevax LP.8.1 pre-filled syringes

* Do not shake.

* Pre-filled syringe should be inspected visually for particulate matter and discolouration prior toadministration.

* Spikevax LP.8.1 is a white to off-white dispersion. It may contain white or translucent product-related particulates. Do not administer if vaccine is discoloured or contains other particulatematter.

* Needles are not included in the pre-filled syringe cartons.

* Use a sterile needle of the appropriate size for intramuscular injection (21-gauge or thinnerneedles).

* With tip cap upright, remove tip cap by twisting counter-clockwise until tip cap releases. Removetip cap in a slow, steady motion. Avoid pulling tip cap while twisting.

* Attach the needle by twisting in a clockwise direction until the needle fits securely on the syringe.

* Uncap the needle when ready for administration.

* Administer the entire dose intramuscularly.

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

MODERNA BIOTECH SPAIN, S.L.

C/ Julián Camarillo nº 3128037 Madrid

Spain

EU/1/20/1507/031

EU/1/20/1507/032

EU/1/20/1507/033

EU/1/20/1507/034

EU/1/20/1507/035

EU/1/20/1507/036

EU/1/20/1507/037

EU/1/20/1507/038

EU/1/20/1507/039

EU/1/20/1507/040

Date of first authorisation: 06 January 2021

Date of latest renewal: 03 October 2022

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

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