These highlights do not include all the information needed to use SPIKEVAX safely and effectively. See full prescribing information for SPIKEVAX. SPIKEVAX (COVID-19 Vaccine, mRNA)Suspension for injection, for intramuscular use 2023-2024 FormulaInitial U.S. Approval: 2022

1 INDICATIONS AND USAGE

SPIKEVAX is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 12 years of age and older.

2 DOSAGE AND ADMINISTRATION

For intramuscular injection only.

2.1 Preparation for Administration

• •SPIKEVAX multiple-dose vials, single dose vials, and single dose pre-filled syringes contain a frozen suspension that does not contain a preservative and must be thawed prior to administration.
• •There are 3 presentations of SPIKEVAX.
• •Thaw each vial or pre-filled syringe before use following the instructions below.

2.2 Administration

Administer SPIKEVAX intramuscularly.

2.3 Dosing and Schedule

SPIKEVAX is administered as a single 0.5 mL dose.

For individuals previously vaccinated with any COVID-19 vaccine, administer the dose of SPIKEVAX at least 2 months after the last dose of COVID-19 vaccine.

3 DOSAGE FORMS AND STRENGTHS

SPIKEVAX is a suspension for injection.

A single dose is 0.5 mL.

4 CONTRAINDICATIONS

Do not administer SPIKEVAX to individuals with a known history of severe allergic reaction (e.g., anaphylaxis) to any component of SPIKEVAX [see Description (11)] or to individuals who had a severe allergic reaction (e.g., anaphylaxis) following a previous dose of a Moderna COVID-19 vaccine.

5 WARNINGS AND PRECAUTIONS

5.1 Management of Acute Allergic Reactions

Appropriate medical treatment must be immediately available to manage potential anaphylactic reactions following administration of SPIKEVAX.

5.2 Myocarditis and Pericarditis

Postmarketing data with authorized or approved mRNA COVID-19 vaccines demonstrate increased risks of myocarditis and pericarditis, particularly within the first week following vaccination. For SPIKEVAX, the observed risk is highest in males 18 years through 24 years of age. Although some cases required intensive care support, available data from short-term follow-up suggest that most individuals have had resolution of symptoms with conservative management. Information is not yet available about potential long-term sequelae.

The Centers for Disease Control and Prevention (CDC) has published considerations related to myocarditis and pericarditis after vaccination, including for vaccination of individuals with a history of myocarditis or pericarditis (https://www.cdc.gov/vaccines/covid-19/clinical-considerations/myocarditis.html).

5.3 Syncope

Syncope (fainting) may occur in association with administration of injectable vaccines. Procedures should be in place to avoid injury from fainting.

5.4 Altered Immunocompetence

Immunocompromised persons, including individuals receiving immunosuppressive therapy, may have a diminished immune response to SPIKEVAX [see Use in Specific Populations (8.6)].

5.5 Limitations of Vaccine Effectiveness

SPIKEVAX may not protect all vaccine recipients.

6 ADVERSE REACTIONS

In clinical studies contributing to the safety assessment of SPIKEVAX, participants received a single dose, a 2-dose series one month apart (referred to as primary series) and subsequent doses referred to as booster doses, as described in Table 1 below.

Most commonly (≥10%) reported adverse reactions following administration of SPIKEVAX or Moderna COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) (hereafter referred to as Moderna COVID-19 Vaccine, Bivalent and no longer authorized for use in the U.S.) containing the same amount of mRNA as the SPIKEVAX 2023-2024 Formula:

• •Participants 12 years through 17 years of age: pain at the injection site (up to 90.6%), fatigue (up to 58.1%), headache (up to 56.3%), myalgia (up to 40.1%), chills (up to 30.2%), axillary swelling/tenderness (up to 27.8%), arthralgia (up to 23.9%), nausea/vomiting (up to 17.9%), and swelling at the injection site (up to 13.3%).
• •Participants 18 years through 64 years of age: pain at injection site (up to 86.3%), fatigue (up to 62.0%), headache (up to 58.9%), myalgia (up to 49.6%), arthralgia (up to 41.9%), chills (up to 40.3%), axillary swelling/tenderness (up to 24.8%), and nausea/vomiting (up to 16.7%).
• •Participants 65 years of age and older: pain at injection site (up to 76.3%), fatigue (up to 58.1%), myalgia (up to 47.4%), headache (up to 42.1%), arthralgia (up to 39.5%), chills (up to 18.4%), and axillary swelling/tenderness (up to 14.3%).

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared with rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.

SPIKEVAX Administered as a Two-Dose Primary Series

Participants 18 Years and Older

The safety of SPIKEVAX was evaluated in an ongoing Phase 3 clinical trial with multiple parts. The randomized, placebo-controlled, observer-blind phase of the trial was conducted in the United States involving 30,346 participants 18 years of age and older who received at least one dose of SPIKEVAX (100 mcg mRNA; n=15,184) or placebo (n=15,162) (Study 1, NCT04470427). Upon issuance of the Emergency Use Authorization (December 18, 2020) for Moderna COVID-19 Vaccine (SPIKEVAX), participants were unblinded in a phased manner over a period of months to offer placebo participants SPIKEVAX. The median duration of follow-up for safety after the second injection during the blinded phase was 4 months. The median duration of follow-up for safety after the second injection including both the blinded phase and the open-label phase was 6 months.

In Study 1, the median age of the population was 52 years (range 18-95); 75.2% of participants were 18 years through 64 years of age and 24.8% were 65 years of age and older. Overall, 52.6% of the participants were male, 47.4% were female, 20.5% were Hispanic or Latino, 79.2% were White, 10.2% were African American, 4.6% were Asian, 0.8% were American Indian or Alaska Native, 0.2% were Native Hawaiian or Pacific Islander, 2.0% were other races, and 2.1% were Multiracial. Demographic characteristics were similar between participants who received SPIKEVAX and those who received placebo.

Solicited Adverse Reactions

Local and systemic adverse reactions and use of antipyretic medication were solicited in an electronic diary for 7 days following each injection (i.e., day of vaccination and the next 6 days) among participants receiving SPIKEVAX (n=15,179) and participants receiving placebo (n=15,159) with at least 1 documented dose. Events that persisted for more than 7 days were followed until resolution. Solicited adverse reactions were reported more frequently among vaccine participants than placebo participants.

The reported number and percentage of the solicited local and systemic adverse reactions by age group and dose are presented in Table 2 and Table 3, respectively.

Solicited local and systemic adverse reactions reported following administration of SPIKEVAX had a median duration of 1 to 3 days.

Grade 3 solicited local adverse reactions were more frequently reported after Dose 2 than after Dose 1. Solicited systemic adverse reactions were more frequently reported by vaccine recipients after Dose 2 than after Dose 1.

In Study 1, 2.3% of participants (vaccine=347, placebo=337) had evidence of prior SARS-CoV-2 infection at baseline (immunologic or virologic evidence of prior SARS-CoV-2 infection [defined as positive RT-PCR test and/or positive Elecsys immunoassay result at Day 1]). Overall, among the 347 vaccine participants, there were no notable differences in reactogenicity compared to the 14,750 vaccine participants who had no evidence of prior SARS-CoV-2 infection at baseline (negative RT-PCR test and negative Elecsys immunoassay result at Day 1).

Unsolicited Adverse Events

Participants were monitored for unsolicited adverse events for 28 days following each dose. Serious adverse events and medically attended adverse events will be recorded for the entire study duration (2 years). Among the 30,346 participants who had received at least 1 dose of vaccine (N=15,184) or placebo (N=15,162), unsolicited adverse events that occurred within 28 days following any vaccination were reported by 31.3% of participants (n=4,752) who received SPIKEVAX and 28.6% of participants (n=4,338) who received placebo.

During the 28-day follow-up period following any dose, lymphadenopathy-related events were reported by 1.7% of vaccine recipients and 0.8% of placebo recipients. These events included lymphadenopathy, lymphadenitis, lymph node pain, vaccination-site lymphadenopathy, injection-site lymphadenopathy, and axillary mass. This imbalance is consistent with the imbalance observed for solicited axillary swelling/tenderness at the injected arm.

During the 7-day follow-up period of any vaccination, hypersensitivity events of injection site rash or injection site urticaria, likely related to vaccination, were reported by 6 participants in the SPIKEVAX group and none in the placebo group. Delayed injection site reactions that began >7 days after vaccination were reported in 1.4% of vaccine recipients and 0.7% of placebo recipients. Delayed injection site reactions included pain, erythema, and swelling and are likely related to vaccination.

In the blinded portion of the study, there were 8 reports of facial paralysis (including Bell’s palsy) in the SPIKEVAX group, and 3 in the placebo group. In the 28-day follow-up period there were two cases of facial paralysis in the SPIKEVAX group, which occurred on 8 and 22 days, respectively, after vaccination, and one in the placebo group, which occurred 17 days after vaccination. Currently available information on facial paralysis is insufficient to determine a causal relationship with the vaccine.

In the blinded portion of the study, there were 50 reports of herpes zoster in the SPIKEVAX group and 23 in the placebo group. In the 28-day period after any vaccination, there were 22 cases of herpes zoster in the SPIKEVAX group and 15 in the placebo group. Currently available information on herpes zoster infection is insufficient to determine a causal relationship with the vaccine.

There were no other notable patterns or numerical imbalances between treatment groups for specific categories of adverse events (including other neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to SPIKEVAX.

Serious Adverse Events

During the blinded phase of the study, serious adverse events were reported by 1.8% (n=268) of participants who received SPIKEVAX and 1.9% (n=292) of participants who received placebo.

There were three serious adverse events of angioedema/facial swelling in the vaccine group in recipients with a history of injection of dermatological fillers. The onset of swelling was reported 1-2 days after the second dose and was likely related to vaccination.

There were no other notable patterns or imbalances between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to SPIKEVAX.

Adolescents 12 Years Through 17 Years of Age

The safety of SPIKEVAX was evaluated in an ongoing Phase 3 clinical trial with multiple parts. The randomized, placebo-controlled, observer-blind clinical trial was conducted in the United States involving 3,726 participants 12 years through 17 years of age who received at least one dose of SPIKEVAX (100 mcg mRNA; n=2,486) or placebo (n=1,240) (Study 3, NCT04649151). Participants started to enter an open-label, observational phase after May 10, 2021. After October 1, 2021, cases of potential myocarditis and/or pericarditis that were identified by the investigator or Applicant were adjudicated by an independent Cardiac Event Adjudication Committee (CEAC) to determine if they met the CDC definition of confirmed or probable myocarditis and/or pericarditis. A safety analysis was conducted in participants who received SPIKEVAX (n=2,486) with a cut-off date of January 31, 2022. In these analyses, the median duration of follow-up including both the blinded and open-label phases was 312 days after Dose 2 and 95.7% of study participants had at least 6 months of follow-up after Dose 2.

Overall, 51.4% were male, 48.6% were female, 11.6% were Hispanic or Latino, 83.8% were White, 3.4% were African American, 6.0% were Asian, 0.5% were American Indian or Alaska Native, <0.1% were Native Hawaiian or Pacific Islander, 1.0% were other races, and 4.5% were Multiracial. Demographic characteristics were similar among participants who received SPIKEVAX and those who received placebo.

Solicited Adverse Reactions

Local and systemic adverse reactions and use of antipyretic medication were solicited in an electronic diary for 7 days following each injection (i.e., day of vaccination and the next 6 days) among participants receiving SPIKEVAX (n=2,485) and participants receiving placebo (n=1,240) with at least 1 documented dose. Events that persisted for more than 7 days were followed until resolution. Solicited adverse reactions were reported more frequently among vaccine participants than placebo participants.

The reported number and percentage of the solicited local and systemic adverse reactions in participants 12 years through 17 years of age by dose are presented in Table 4.

Solicited local and systemic adverse reactions reported following administration of SPIKEVAX had a median duration of 2 to 3 days.

In ages 12 years through 17 years, 5.8% of participants (vaccine=147, placebo=70) had evidence of prior SARS-CoV-2 infection at baseline (immunologic or virologic evidence of prior SARS-CoV-2 infection [defined as positive RT-PCR test and/or positive Elecsys immunoassay result at Day 1]). An assessment of reactogenicity among participants with evidence of prior SARS-CoV-2 infection compared to those with no evidence of infection at baseline (negative RT-PCR test and negative Elecsys immunoassay result at Day 1) was conducted. Table 5 presents the number and percentage of the solicited local and systemic adverse reactions in SPIKEVAX participants starting within 7 days after each dose by SARS-CoV-2 status.

Unsolicited Adverse Events

Participants were monitored for unsolicited adverse events for 28 days following each dose. Serious adverse events and medically attended adverse events were recorded for the entire study duration. Among the 3,726 participants who had received at least 1 dose of vaccine (n=2,486) or placebo (n=1,240), unsolicited adverse events that occurred within 28 days following any vaccination were reported by 23.4% of participants (n=582) who received SPIKEVAX and 19.1% of participants (n=237) who received placebo.

In the open-label portion of the study, a 14-year-old male experienced probable myocarditis with onset of symptoms 1 day after Dose 2 of SPIKEVAX. Symptoms resolved after 8 days and no sequelae were observed at 5 months. This event was considered related to SPIKEVAX and was subsequently adjudicated by the CEAC as probable myocarditis. There were no cases of myocarditis among placebo recipients.

During the 28-day follow-up period following any dose, lymphadenopathy-related events were reported by 6.0% of vaccine recipients and 0.6% of placebo recipients. These events included lymphadenopathy, vaccination-site lymphadenopathy, and injection-site lymphadenopathy which were plausibly related to vaccination. This imbalance is consistent with the imbalance observed for solicited axillary swelling/tenderness in the injected arm.

During the 28-day follow-up period following any dose, hypersensitivity events of injection site rash or injection site urticaria, likely related to vaccination, were reported by 0.3% of participants in the SPIKEVAX group and <0.1% in the placebo group. Delayed injection site reactions that began >7 days after vaccination were reported in 1.5% of vaccine recipients and in <0.1% of placebo recipients. Delayed injection site reactions included pain, erythema, and swelling and are likely related to vaccination.

There were no other notable patterns or numerical imbalances between treatment groups for specific categories of adverse events (including other neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to SPIKEVAX.

Serious Adverse Events

During the blinded portion of the study, serious adverse events were reported by 0.4% (n=9) of participants who received SPIKEVAX and 0.2% (n=3) of participants who received placebo. In the open-label phase, an additional 12 SPIKEVAX recipients reported serious adverse events. There were no serious adverse events considered causally related to the vaccine.

There were no notable patterns or imbalances between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to SPIKEVAX.

SPIKEVAX Administered as a First Booster Dose Following a Primary Series of SPIKEVAX

Participants 18 Years and Older

Safety data for SPIKEVAX administered as a first booster dose following a primary series of SPIKEVAX in participants 18 years of age and older were evaluated in two clinical studies.

Study 2

Study 2 was a Phase 2, randomized, observer-blind, placebo-controlled, dose-confirmation study to evaluate the safety, reactogenicity, and immunogenicity of SPIKEVAX in participants 18 years of age and older (NCT04405076). In this study, 198 participants received two doses 1 month apart of SPIKEVAX primary series (100 mcg mRNA per dose). In an open-label phase of the study, 171 of those participants received a single booster dose (50 mcg mRNA) at least 6 months (range of 5.8 to 8.5 months) after receiving the second dose of the primary series.

Among the 171 booster dose recipients, the median age was 55 years (range 18-87); 77.8% of participants were 18 years through 64 years of age, 22.2% were 65 years of age and older, 39.2% were male, 60.8% were female, 5.8% were Hispanic or Latino, 95.9% were White, 2.9% were African American, 0.6% were Asian, and 0.6% were American Indian or Alaska Native.

Solicited Adverse Reactions

Solicited local and systemic adverse reactions in participants 18 years through 64 years of age starting within 7 days after administration of a booster dose included pain at the injection site (86.0%), fatigue (62.0%), headache (58.9%), myalgia (49.6%), arthralgia (41.9%), chills (40.3%), axillary swelling/tenderness (24.8%), nausea/vomiting (12.4%), fever (7.0%), swelling at the injection site (6.2%), erythema at the injection site (5.4%), and rash (2.3%).

Solicited local and systemic adverse reactions in participants 65 years of age and older starting within 7 days after administration of a booster dose included pain at the injection site (76.3%), fatigue (47.4%), myalgia (47.4%), headache (42.1%), arthralgia (39.5%), chills (18.4%), nausea/vomiting (7.9%), fever (5.4%), axillary swelling/tenderness (5.3%), erythema at the injection site (2.6%), and swelling at the injection site (2.6%).

No Grade 4 adverse reactions were reported. The median duration of solicited local and systemic adverse reactions was 2 to 3 days.

Unsolicited Adverse Events

Overall, the 171 participants who received a booster dose had a median follow-up time of 176 days after the booster dose to the database lock date (November 23, 2021). Through 28 days after the booster dose, unsolicited adverse events were reported by 14.6% of participants (n=25) after the booster dose. There were no unsolicited adverse events not already captured by solicited local and systemic reactions that were considered causally related to SPIKEVAX.

Serious Adverse Events

There were no serious adverse events reported from the booster dose through 28 days after the booster dose. Through the database lock date (November 23, 2021), there were no serious adverse events following the booster dose considered causally related to SPIKEVAX.

Study 1

Study 1 is an ongoing Phase 3 clinical trial with multiple parts to evaluate the safety, reactogenicity, and immunogenicity of SPIKEVAX in participants 18 years of age and older (NCT04470427). In the open-label booster dose phase of this study, 19,609 participants received a single booster dose of SPIKEVAX (50 mcg mRNA). Of these participants, 19,599 had previously received a primary series of SPIKEVAX and received a single booster dose at least 6 months (range of 5 to 19 months) after receiving the second dose of the primary series.

Among the 19,609 booster dose recipients, the median age was 55 years (range 19-96); 69.6% of participants were 18 years through 64 years of age, 30.4% were 65 years of age and older, 52.4% were male, 47.6% were female, 20.2% were Hispanic or Latino, 78.9% were White, 10.6% were African American, 4.1% were Asian, 0.8% were American Indian or Alaska Native, 0.2% were Native Hawaiian or Pacific Islander, 2.0% were other races, and 2.2% were Multiracial. After October 1, 2021, cases of potential myocarditis and/or pericarditis that were identified by the investigator or Applicant were adjudicated by an independent CEAC to determine if they met the CDC definition of confirmed or probable myocarditis and/or pericarditis. In these analyses, the median follow-up time after the booster dose through the cutoff date (April 5, 2022) was 161 days and 3,361 study participants who received the booster dose (17.1%) had at least 6 months of follow-up.

Unsolicited Adverse Events

Participants were monitored for unsolicited adverse events for up to 28 days following the booster dose. As of the cut-off date (April 5, 2022), among the 19,609 participants who had received a booster dose, unsolicited adverse events that occurred within 28 days after the booster were reported by 31.7% of participants (n=6,209). The safety profile for the booster dose of SPIKEVAX was similar to the safety profile of the SPIKEVAX primary series in this population.

Serious Adverse Events

Serious adverse events through 28 days following the booster dose of SPIKEVAX were reported by 0.5% of participants (n=94). Through the cut-off date (April 5, 2022), 2.3% of participants (n=442) reported serious adverse events following the booster dose.

A 42-year-old male experienced probable myocarditis (per CEAC adjudication) with onset of symptoms the same day following receipt of the booster dose of SPIKEVAX. Myocarditis was reported as resolved without sequelae on Day 72. This event was considered related to SPIKEVAX.

There was one serious adverse event of erythema nodosum 8 days after the booster dose in a 73-year-old female. This event was considered causally related to SPIKEVAX and was reported as resolved without treatment on Day 30.

Adolescents 12 Years Through 17 Years of Age

Safety data for a booster dose of SPIKEVAX in adolescents were collected in an ongoing Phase 3 clinical trial with multiple parts. The open-label booster portion of the study included 1,405 participants who were 12 years through 17 years of age at the time of first dose of the primary series and who received a booster dose of SPIKEVAX (50 mcg mRNA) at least 5 months (range 2.1 to 16.9 months) after the second dose of the primary series (Study 3, NCT04649151). Overall, 51.5% were male, 48.5% were female, 13.4% were Hispanic or Latino, 84.9% were White, 3.1% were African American, 4.9% were Asian, 0.5% were American Indian or Alaska Native, <0.1% were Native Hawaiian or Pacific Islander, 0.7% were other races, and 5.2% were Multiracial. The median duration of follow-up for safety after the booster dose was 204 days.

Solicited Adverse Reactions

Local and systemic adverse reactions and use of antipyretic medication were solicited in an electronic diary for 7 days following the injection (i.e., day of vaccination and the next 6 days) among participants receiving SPIKEVAX as a booster dose. Events that persisted for more than 7 days were followed until resolution.

Table 6 presents the frequency and severity of reported solicited local and systemic adverse reactions among SPIKEVAX booster dose recipients 12 years through 17 years of age within 7 days of a booster vaccination.

In participants who received a booster dose, the median duration of solicited local and systemic adverse reactions was 2 to 3 days.

Unsolicited Adverse Events

Participants were monitored for unsolicited adverse events for up to 28 days following the booster dose. Serious adverse events and medically attended adverse events were recorded for the entire study duration. As of August 15, 2022, among the 1,405 participants who had received a booster dose of SPIKEVAX, unsolicited adverse events that occurred within 28 days following vaccination were reported by 14.9% of participants (n=209). In these analyses, 85.7% of study participants had at least 6 months of follow-up after the booster dose. Overall, there were no notable differences in the safety profiles observed between participants who had received a booster dose of SPIKEVAX and those who had received a primary series.

Serious Adverse Events

Through the cut-off date of August 15, 2022, with a median follow-up duration of 204 days after the booster dose, there were no serious adverse events considered causally related to the vaccine.

Moderna COVID-19 Vaccine, Bivalent Administered as a Second Booster Dose in Participants 18 Years and Older

Study 5 (NCT04927065), a Phase 2/3 open-label study with multiple parts conducted in the United States, evaluated the immunogenicity, safety, and reactogenicity of a second booster dose of Moderna COVID-19 Vaccine, Bivalent (50 mcg mRNA) compared to a second booster dose of SPIKEVAX (50 mcg mRNA) when administered to participants 18 years of age and older who had previously received a primary series and a first booster dose with SPIKEVAX at least 3 months prior. The safety analysis set included 511 participants in the Moderna COVID-19 Vaccine, Bivalent booster dose group and 376 participants in the SPIKEVAX booster dose group.

For the Moderna COVID-19 Vaccine, Bivalent group, the median age of the population was 50 years (range 19-89); 79.5% of participants were 18 years through 64 years of age and 20.5% were 65 years of age and older. Overall, 38.2% were male, 61.8% were female, 11.4% were Hispanic or Latino, 83.4% were White, 11.0% were African American, 2.2% were Asian, 0.2% were American Indian or Alaska Native, 1.2% were other races, and 1.6% were Multiracial. For the SPIKEVAX group, the median age of the population was 61 years (range 20-96); 60.1% of participants were 18 years through 64 years of age and 39.9% were 65 years of age and older. Overall, 49.5% were male, 50.5% were female, 9.8% were Hispanic or Latino, 85.6% were White, 7.4% were African American, 4.3% were Asian, 0.3% were American Indian or Alaska Native, 0.3% were Native Hawaiian or Pacific Islander, 0.5% were other races, and 0.5% were Multiracial.

In these analyses, the median follow-up time after the booster dose through the cutoff date (September 23, 2022) for the Moderna COVID-19 Vaccine, Bivalent recipients was 37 days. The median follow-up time after the booster dose through the cutoff date (July 6, 2022) for the SPIKEVAX recipients was 127 days.

Solicited Adverse Reactions

Local and systemic adverse reactions and use of antipyretic medication were solicited in an electronic diary for 7 days following each injection (i.e., day of vaccination and the next 6 days) among participants receiving Moderna COVID-19 Vaccine, Bivalent and participants receiving SPIKEVAX. Events that persisted for more than 7 days were followed until resolution.

Table 7 and Table 8 present the frequency and severity of reported solicited local and systemic adverse reactions within 7 days following a second booster dose with Moderna COVID-19 Vaccine, Bivalent compared to SPIKEVAX in participants 18 years through 64 years of age and 65 years of age and older.

The median duration of solicited local and systemic adverse reactions was 3 days in participants who received either vaccine booster dose.

Unsolicited Adverse Events

Participants were monitored for unsolicited adverse events for up to 28 days following the booster dose. Serious adverse events and medically attended adverse events will be recorded for the entire study duration. As of September 23, 2022, among participants who had received a booster dose of Moderna COVID-19 Vaccine, Bivalent (n=511), unsolicited adverse events that occurred within 28 days following vaccination were reported by 22.7% of participants (n=116). As of July 6, 2022, among participants who had received a booster dose of SPIKEVAX (n=376), unsolicited adverse events that occurred within 28 days following vaccination were reported by 21.3% of participants (n=80). In these analyses, 99.6% of study participants in the Moderna COVID-19 Vaccine, Bivalent group had at least 28 days of follow-up after the booster dose to the cut-off date (September 23, 2022) and 100.0% of participants in the SPIKEVAX group had at least 28 days of follow-up after the booster dose to the cutoff date (July 6, 2022). There were no notable differences in specific categories of adverse events that were reported between the vaccine groups.

Serious Adverse Events

As of the cutoff date (September 23, 2022), the median duration of follow-up was 37 days among Moderna COVID-19 Vaccine, Bivalent booster dose recipients. Serious adverse events were reported by 0.6% of participants (n=3) who received Moderna COVID-19 Vaccine, Bivalent. As of the cutoff date (July 6, 2022), the median duration of follow-up was 127 days among the SPIKEVAX booster dose recipients. Serious adverse events were reported by 2.7% of participants (n=10) who received SPIKEVAX. None of the events in either vaccine group were considered to be related to vaccine.

Moderna COVID-19 Vaccine, Bivalent Administered as a Single Dose in Participants 12 Years Through 17 Years of Age

Safety data for a single dose of Moderna COVID-19 Vaccine, Bivalent in adolescents were collected in an ongoing Phase 3 clinical trial with multiple parts. The open-label single dose portion of the study conducted in the United States and the Dominican Republic included 379 participants 12 years through 17 years of age who were COVID-19 vaccine-naïve and received a single 50 mcg dose of Moderna COVID-19 Vaccine, Bivalent (Study 3, NCT04649151). Overall, 52.8% were male, 47.2% were female, 94.5% were Hispanic or Latino, 10.3% were White, 32.2% were African American or Black, 56.7% were other races, and 0.8% were Multiracial. Of the 379 participants, 99.7% had evidence of prior SARS-CoV-2 infection at baseline (immunologic or virologic evidence of prior SARS-CoV-2 infection [defined as positive RT-PCR test and/or positive Elecsys immunoassay result at Day 1]). The median duration of follow-up for safety after vaccination was 35 days.

Solicited Adverse Reactions

Local and systemic adverse reactions and use of antipyretic medication were solicited in an electronic diary for 7 days following the injection (i.e., day of vaccination and the next 6 days) among participants receiving a single dose of Moderna COVID-19 Vaccine, Bivalent. Events that persisted for more than 7 days were followed until resolution.

Table 9 presents the frequency and severity of reported solicited local and systemic adverse reactions among Moderna COVID-19 Vaccine, Bivalent single dose recipients 12 years through 17 years of age within 7 days of vaccination.

The median duration of solicited local and systemic adverse reactions was 2 days.

Unsolicited Adverse Events

Participants were monitored for unsolicited adverse events for up to 28 days vaccination. Serious adverse events and medically attended adverse events will be recorded for the entire study duration. As of June 5, 2023, among the 379 participants who had received a single dose of Moderna COVID-19 Vaccine, Bivalent, unsolicited adverse events that occurred within 28 days following vaccination were reported by 12.9% of participants (n=49). In these analyses, 68.9% of study participants had at least 28 days of follow-up after vaccination. There were no unsolicited adverse events not already captured by solicited local and systemic reactions that were considered causally related to SPIKEVAX.

Serious Adverse Events

Through the cut-off date of June 5, 2023, with a median follow-up duration of 35 days after vaccination, serious adverse events were reported by 0.8% of participants (n=3). None of these events were considered to be related to vaccine.

6.2 Postmarketing Experience

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

Cardiac Disorders: myocarditis, pericarditisImmune System Disorders: anaphylaxis, urticariaNervous System Disorders: syncope

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to SPIKEVAX during pregnancy. Women who are vaccinated with SPIKEVAX during pregnancy are encouraged to enroll in the registry by calling 1-866-MODERNA (1-866-663-3762).

Risk Summary

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

A developmental toxicity study was performed in female rats administered the equivalent of a single primary series dose of SPIKEVAX twice prior to mating and twice during gestation. The study revealed no evidence of harm to the fetus due to the vaccine (see Animal Data).

Data

Animal Data

In a developmental toxicity study, 0.2 mL of a vaccine formulation containing the same quantity of nucleoside-modified messenger ribonucleic acid (mRNA) (100 mcg) and other ingredients included in a single primary series dose of SPIKEVAX for individuals 12 years of age and older was administered to female rats by the intramuscular route on four occasions: 28 and 14 days prior to mating, and on gestation days 1 and 13. No vaccine-related fetal malformations or variations and no adverse effect on postnatal development were observed in the study.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Pregnant individuals infected with SARS-CoV-2 are at increased risk of severe COVID-19 compared with non-pregnant individuals.

8.2 Lactation

Risk Summary

It is not known whether SPIKEVAX is excreted in human milk. Data are not available to assess the effects of SPIKEVAX on the breastfed infant or on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SPIKEVAX and any potential adverse effects on the breastfed infant from SPIKEVAX or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.

8.4 Pediatric Use

Safety and effectiveness of SPIKEVAX have not been established in individuals less than 12 years of age. Evidence from clinical studies in individuals 6 months through 23 months of age strongly suggest that a single dose of SPIKEVAX would be ineffective in individuals younger than 2 years of age.

8.5 Geriatric Use

Clinical studies of SPIKEVAX and Moderna COVID-19 Vaccine, Bivalent included approximately 7,800 participants 65 years of age and older and 1,400 participants 75 years of age and older [see Adverse Reactions (6.1) and Clinical Studies (14)].

Some local and systemic adverse reactions were reported in a lower proportion of participants 65 years of age and older compared to participants 18 years through 64 years of age [see Adverse Reactions (6.1)].

Vaccine effectiveness was similar between participants 65 years of age and older and participants 18 years through 64 years [see Clinical Studies (14.1 and 14.6)].

8.6 Immunocompromised Individuals

The Centers for Disease Control and Prevention has published considerations related to COVID-19 vaccination for individuals who are moderately to severely immunocompromised (https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html).

11 DESCRIPTION

SPIKEVAX (COVID-19 Vaccine, mRNA) is a sterile white to off-white suspension for intramuscular injection.

Each 0.5 mL dose of SPIKEVAX (2023-2024 Formula) contains 50 mcg nucleoside-modified messenger RNA (mRNA) encoding the pre-fusion stabilized Spike glycoprotein (S) of the SARS-CoV-2 Omicron variant lineage XBB.1.5. Each dose also contains the following ingredients: a total lipid content of 1.01 mg (SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC]), 0.25 mg tromethamine, 1.2 mg tromethamine hydrochloride, 0.021 mg acetic acid, 0.10 mg sodium acetate trihydrate, and 43.5 mg sucrose.

SPIKEVAX does not contain a preservative.

The vial stoppers and rubber tip cap and plunger used for the single dose syringes are not made with natural rubber latex.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The nucleoside-modified mRNA in SPIKEVAX is formulated in lipid particles, which enable delivery of the nucleoside-modified mRNA into host cells to allow expression of the SARS-CoV-2 S antigen. The vaccine elicits an immune response to the S antigen, which protects against COVID-19.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

SPIKEVAX has not been evaluated for carcinogenic, mutagenic potential, or impairment of male fertility in animals. A developmental toxicity study was conducted in female rats that received a vaccine formulation containing nucleoside-modified messenger ribonucleic acid (mRNA) (100 mcg) and other ingredients included in a single human dose of SPIKEVAX. No impact on female fertility was reported (see Use in Specific Populations [8.1]).

14 CLINICAL STUDIES

14.1 Efficacy of SPIKEVAX Two-Dose Primary Series in Participants 18 Years of Age and Older

Study 1 is an ongoing Phase 3 clinical trial with multiple parts. The randomized, placebo-controlled, observer-blind phase evaluated the efficacy, safety, and immunogenicity of SPIKEVAX in participants 18 years of age and older in the United States. Randomization was stratified by age and health risk: 18 to <65 years of age without comorbidities (not at risk for progression to severe COVID-19), 18 to <65 years of age with comorbidities (at risk for progression to severe COVID-19), and 65 years of age and older with or without comorbidities. Participants who were immunocompromised and those with a known history of SARS-CoV-2 infection were excluded from the study. Participants with no known history of SARS-CoV-2 infection but with positive laboratory results indicative of infection at study entry were included. The study allowed for the inclusion of participants with stable pre-existing medical conditions, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrollment, as well as participants with stable human immunodeficiency virus (HIV) infection. A total of 30,415 participants were randomized equally to receive 2 doses of SPIKEVAX or saline placebo 1 month apart. Participants will be followed for efficacy and safety until 2 years after the second dose.

The primary efficacy analysis population (referred to as the Per-Protocol Set) included 28,451 participants who received two doses (at 0 and 1 month) of either SPIKEVAX (100 mcg mRNA per dose; n=14,287) or placebo (n=14,164), and had a negative baseline SARS-CoV-2 status. In the Per-Protocol Set, 47.5% of participants were female, 19.7% were Hispanic or Latino; 79.7% were White, 9.7% were African American, 4.7% were Asian, and 2.0% were other races. The median age of participants was 53 years (range 18-95) and 25.4% of participants were 65 years of age and older. Of the study participants in the Per-Protocol Set, 22.8% were at increased risk of severe COVID-19 due to at least one pre-existing medical condition (chronic lung disease, significant cardiac disease, severe obesity, diabetes, liver disease, or HIV infection) regardless of age. There were no notable differences in demographics or pre-existing medical conditions between participants who received SPIKEVAX and those who received placebo.

The population for the vaccine efficacy analysis included participants 18 years of age and older who were enrolled from July 27, 2020, and followed for the development of COVID-19 through the data cutoff of March 26, 2021, or the Participant Decision Visit for treatment unblinding, whichever was earlier. The median length of follow-up for participants in the blinded placebo-controlled phase of the study was 4 months following Dose 2.

Efficacy Against COVID-19

COVID-19 was defined based on the following criteria: The participant must have experienced at least two of the following systemic symptoms: fever (≥38ºC / ≥100.4ºF), chills, myalgia, headache, sore throat, new olfactory and taste disorder(s); or the participant must have experienced at least one of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, or clinical or radiographical evidence of pneumonia; and the participant must have at least one NP swab, nasal swab, or saliva sample (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by RT-PCR. COVID-19 cases were adjudicated by a Clinical Adjudication Committee.

There were 55 COVID-19 cases in the SPIKEVAX group and 744 cases in the placebo group, with a vaccine efficacy of 93.2% (95% confidence interval of 91.0% to 94.8%) (Table 10).

SARS-CoV-2 identified in the majority of COVID-19 cases in this study were sequenced to be the B.1.2 variant. Additional SARS-CoV-2 variants identified in this study included B.1.427/B.1.429 (Epsilon), P.1 (Gamma), and P.2 (Zeta). Representation of identified variants among cases in the vaccine versus placebo recipients did not suggest decreased vaccine effectiveness against these variants.

Severe COVID-19 was defined based on confirmed COVID-19 as per the primary efficacy endpoint case definition, plus any of the following: Clinical signs indicative of severe systemic illness, respiratory rate ≥30 per minute, heart rate ≥125 beats per minute, SpO2 ≤93% on room air at sea level or PaO2/FIO2 <300 mm Hg; or respiratory failure or ARDS (defined as needing high-flow oxygen, non-invasive or mechanical ventilation, or ECMO), evidence of shock (systolic blood pressure <90 mmHg, diastolic BP <60 mmHg or requiring vasopressors); or significant acute renal, hepatic, or neurologic dysfunction; or admission to an intensive care unit or death.

Among all participants in the Per-Protocol Set analysis, which included COVID-19 cases confirmed by an adjudication committee, 2 cases of severe COVID-19 were reported in the SPIKEVAX group compared with 106 cases reported in the placebo group, with a vaccine efficacy of 98.2% (95% confidence interval of 92.8% to 99.6%) (Table 11).

In an exploratory analysis, occurrence of asymptomatic SARS-CoV-2 infection was assessed among participants in the Per-Protocol Set (enrolled from July 27, 2020, and followed maximally through March 26, 2021). Asymptomatic SARS-CoV-2 infection was defined as having a positive scheduled serology test based on binding antibody against SARS-CoV-2 nucleocapsid protein as measured by the Roche Elecsys immunoassay (N-serology) and/or a positive RT-PCR test for SARS-CoV-2, in the absence of any reported COVID-19 symptoms included as part of the primary efficacy endpoint case definition (described above) or symptoms included in the secondary COVID-19 endpoint case definition (fever >38°C / ≥100.4°F, chills, cough, shortness of breath or difficulty breathing, fatigue, muscle aches, body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea, vomiting, or diarrhea) at any time during the study. To assess for asymptomatic infection starting 14 days after Dose 2, all participants had scheduled blood draws for N-serology collected at the 1-month post-Dose 2 visit and the 6-month post-Dose 2 visit (if still blinded to treatment arm), and scheduled N-serology and nasopharyngeal swab for RT-PCR collection at the Participant Decision Visit for treatment unblinding.

In the Per-Protocol Set, 14,287 participants in the SPIKEVAX group and 14,164 participants in the placebo group had N-serology and/or RT-PCR results available from one or more of the pre-specified timepoints listed above. Among these participants, there were 180 cases of asymptomatic SARS-CoV-2 infection in the SPIKEVAX group compared with 399 cases in the placebo group. Limitations of this analysis include the infrequently scheduled assessments for serology and PCR testing, which may not have captured all cases of asymptomatic infections which occurred during the study.

14.2 Effectiveness of SPIKEVAX Two-Dose Primary Series in Participants 12 Years Through 17 Years of Age

Study 3 is an ongoing Phase 3 clinical trial with multiple parts. The randomized, placebo-controlled, observer-blind phase evaluated the safety, reactogenicity, and effectiveness of SPIKEVAX in participants ages 12 years through 17 years in the United States. Participants with a known history of SARS-CoV-2 infection were excluded from the study. A total of 3,733 participants were randomized 2:1 to receive 2 doses of SPIKEVAX (100 mcg mRNA per dose) or saline placebo 1 month apart. Among participants assessed for immunogenicity, 52.4% of participants were male, 47.6% were female, 7.6% were Hispanic or Latino; 83.5% were White, 1.2% were African American, 4.4% were Asian, 0.3% were Native Hawaiian or Pacific Islander, 2.1% were other races, and 5.6% were Multiracial.

Effectiveness in individuals 12 years through 17 years of age is based on a comparison of immune responses in this age group to adults 18 years through 25 years of age.

In Study 3, an analysis was conducted of SARS-CoV-2 50% neutralizing titers and seroresponse rates 28 days after Dose 2 in a subset of participants 12 years through 17 years of age in Study 3 and participants 18 years through 25 years of age in Study 1 who had no immunologic or virologic evidence of prior SARS-CoV-2 at baseline. Noninferior immune responses as assessed by geometric mean 50% neutralizing titers and seroresponse rates were demonstrated in a comparison of participants 12 years through 17 years of age to participants 18 years through 25 years of age (Table 12).

A descriptive efficacy analysis evaluating confirmed COVID-19 cases accrued up to the blinded data cutoff date of May 31, 2021, was performed in 3,186 participants who received two doses (at 0 and 1 month) of either SPIKEVAX (n=2,142) or placebo (n=1,044) and had a negative baseline SARS-CoV-2 status (referred to as the Per-Protocol Set for Efficacy). In the Per-Protocol Set for Efficacy, 51.5% were male, 48.5% were female, 11.0% were Hispanic or Latino; 84.0% were White, 2.7% were African American, 6.2% were Asian, 0.5% were American Indian or Alaska Native, <0.1% were Native Hawaiian or Pacific Islander, 0.9% were other races, and 4.8% were Multiracial. There were no notable differences in demographics between participants who received SPIKEVAX and those who received placebo.

The population for the vaccine efficacy analysis included participants 12 years through 17 years of age who were enrolled from December 9, 2020, and followed for the development of COVID-19 through the data cutoff of May 31, 2021. The median length of follow-up for participants in the blinded, placebo-controlled phase of the study was 112 days following Dose 2.

The efficacy information in participants 12 years through 17 years of age is presented in Table 13.

14.3 Immunogenicity of a Single Dose of Moderna COVID-19 Vaccine, Bivalent in COVID-19 Vaccine-Naïve Individuals with Evidence of Prior SARS-CoV-2 Infection

In an open-label phase of Study 3 conducted in the United States and the Dominican Republic, participants 12 years through 17 years of age who were COVID-19 vaccine-naïve received a single dose (50 mcg mRNA) of Moderna COVID-19 Vaccine, Bivalent. Of the 246 participants in the immunogenicity subset, 99.6% had evidence of prior SARS-CoV-2 infection at baseline (immunologic or virologic evidence of prior SARS-CoV-2 infection [defined as positive RT-PCR test and/or positive Elecsys immunoassay result at Day 1]). The primary immunogenicity analysis population included 245 participants who were baseline SARS-COV-2 positive in Study 3 and a subset of 296 participants 18 years through 25 years of age from Study 1 who had no evidence of prior SARS-CoV-2 infection at baseline and received two doses (100 mcg mRNA per dose) of SPIKEVAX 1 month apart. Among participants 12 years through 17 years of age assessed for immunogenicity, 53.5% were male, 46.5% were female, 94.3% were Hispanic or Latino, 14.3% were White, 33.9% were African American or Black, 51.0% were other races, and 0.8% were Multiracial.

A comparison of neutralizing antibody concentrations against a pseudovirus expressing Omicron BA.4/BA.5 and the original SARS-CoV-2 Spike protein (D614G) was conducted. The primary immunogenicity analyses of the GMC ratio following the single dose in Study 3 compared to after the primary series in Study 1 met the pre-defined success criteria for superiority against Omicron BA.4/BA.5 and noninferiority against the Original strain. Secondary analyses included the difference in seroresponse rates, where seroresponse for a participant was defined as achieving a ≥4-fold rise of neutralizing antibody concentration from baseline (before the first dose of the primary series in Study 1 and the single dose in Study 3). These analyses are summarized in Table 14.

14.4 Immunogenicity of SPIKEVAX Administered as a First Booster Dose Following a SPIKEVAX Primary Series in Participants 18 Years of Age and Older

Effectiveness of a booster dose of SPIKEVAX was based on assessment of neutralizing antibody geometric mean concentration (GMC) against a pseudovirus expressing the original SARS-CoV-2 Spike protein (D614G). Immunogenicity analyses compared the GMC following the booster dose to the GMC following the primary series.

In the open-label booster dose phase of Study 1, the primary immunogenicity analysis population included 682 participants 18 years of age and older who received a single booster dose of SPIKEVAX (50 mcg mRNA) at least 6 months after completion of the primary series of SPIKEVAX (two doses of 100 mcg mRNA 1 month apart). Participants had no serologic or virologic evidence of SARS-CoV-2 infection prior to the first primary series dose and prior to the booster dose. Among participants assessed for immunogenicity, the median age at the time of booster dose was 59 years (range 19-87); 61.3% of participants were 18 years through 64 years of age, 38.7% were 65 years of age and older, 52.9% were male, 47.1% were female, 30.4% were Hispanic or Latino; 70.8% were White, 19.6% were African American, 2.5% were Asian, 1.3% were American Indian or Alaska Native, 0.4% were Native Hawaiian or Pacific Islander, 3.1% were other races, and 1.3% were Multiracial.

The primary immunogenicity analyses of the GMC ratio and difference in seroresponse rates following the booster dose compared to after the primary series met the pre-defined success criteria. Seroresponse for a participant was defined as achieving a ≥4-fold rise of neutralizing antibody concentration from baseline (before the first dose of the primary series). These analyses are summarized in Table 15.

A descriptive analysis evaluated seroresponse rates using pre-booster neutralizing antibody concentration. The booster dose seroresponse rate, with seroresponse defined as at least a 4-fold rise relative to the pre-booster concentration, was 98.4%. The difference in seroresponse rates in this post-hoc analysis was -0.8% (95% CI -2.1, 0.5).

14.5 Immunogenicity of SPIKEVAX Booster Dose Following SPIKEVAX Primary Series in Participants 12 Years Through 17 Years of Age

Effectiveness of a booster dose of SPIKEVAX in participants 12 years through 17 years of age was based on a comparison of immune responses, as assessed by neutralizing antibody concentration against a pseudovirus expressing the original SARS-CoV-2 Spike protein (D614G), following the booster dose in this age group to that following the primary series in adults 18 years through 25 years of age.

In an open-label booster phase of Study 3, participants who were 12 years through 17 years of age at the time of first dose of a primary series received a single booster dose of SPIKEVAX (50 mcg mRNA) at least 5 months (range 2.1 to 16.9) after completion of the primary series (two doses 1 month apart). The primary immunogenicity analysis population included 264 booster dose participants in Study 3 and a random subset of 295 participants 18 years through 25 years of age from Study 1 who received two doses of SPIKEVAX 1 month apart. Study 1 and Study 3 participants 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. Among participants 12 years through 17 years of age assessed for immunogenicity, 50.8% were male, 49.2% were female, 12.5% were Hispanic or Latino; 87.9% were White, 1.5% were African American, 3.4% were Asian, 1.1% were other races, and 5.7% were Multiracial.

The primary immunogenicity analyses of the GMC ratio and difference in seroresponse rates following the booster dose in Study 3 compared to after the primary series in Study 1 met the pre-defined success criteria. Seroresponse for a participant was defined as achieving a ≥4-fold rise of neutralizing antibody concentration from baseline (before the first dose of the primary series in Study 1 and Study 3). These analyses are summarized in Table 16.

A descriptive analysis evaluated seroresponse rates using pre-booster neutralizing antibody concentration. The booster dose seroresponse rate, with seroresponse defined as at least a 4-fold rise relative to the pre-booster concentration, was 96.6%. The difference in seroresponse rates in this post-hoc analysis was -2.7% (95% CI -5.8, -0.5).

14.6 Immunogenicity of Moderna COVID-19 Vaccine, Bivalent Administered as a Second Booster Dose in Participants 18 Years of Age and Older

Study 5 is a Phase 2/3 open-label study with multiple parts which evaluated the immunogenicity of a second booster dose of Moderna COVID-19 Vaccine, Bivalent (50 mcg mRNA) compared to a second booster dose of SPIKEVAX (50 mcg mRNA) when administered to participants 18 years of age and older who had previously received a primary series and a first booster dose with SPIKEVAX at least 3 months prior. The primary immunogenicity analysis population included 209 participants who received a booster dose of Moderna COVID-19 Vaccine, Bivalent and 259 participants who received a booster dose of SPIKEVAX. Participants included in the analysis population had no serologic or virologic evidence of SARS-CoV-2 infection prior to the second booster dose.

Among participants assessed for immunogenicity for the Moderna COVID-19 Vaccine, Bivalent group, the median age was 51 years (range 21-84); 74.6% of participants were 18 years through 64 years of age, 25.4% were 65 years of age and older, 35.4% were male, 64.6% were female, 9.6% were Hispanic or Latino, 89.0% were White, 5.3% were African American, 3.3% were Asian, 0.5% were American Indian or Alaska Native, 0.5% were other races, and 1.0% were Multiracial. Among participants assessed for immunogenicity for the SPIKEVAX group, the median age was 63 years (range 21-96); 53.7% of participants were 18 years through 64 years of age, 46.3% were 65 years of age and older, 48.3% of participants were male, 51.7% were female, 8.5% were Hispanic or Latino, 90.0% were White, 4.2% were African American, 4.2% were Asian, and 0.4% were other races. The median time between the first booster dose and the second booster dose was 288 days in the Moderna COVID-19 Vaccine, Bivalent group and 133 days in the SPIKEVAX group.

In Study 5, the neutralizing antibody titers (50% inhibitory dose [ID50]) against a pseudovirus expressing the original SARS-CoV-2 Spike protein (D614G) and a pseudovirus expressing the Omicron BA.4/BA.5 Spike protein were evaluated. Primary immunogenicity analyses compared the ID50 GMTs and seroresponse rates 28 days following a second booster dose with Moderna COVID-19 Vaccine, Bivalent to those following a second booster dose with SPIKEVAX. Analyses of GMTs met predefined success criteria for superiority against Omicron BA.4/BA.5 and noninferiority against the Original strain. The analysis of seroresponse against Omicron BA.4/BA.5 met the criterion for noninferiority: Lower limit of the 2-sided 95% CI for the percentage difference in seroresponse rate (Moderna COVID-19 Vaccine, Bivalent minus SPIKEVAX) >-10%. Table 17 presents the analyses of ID50 GMTs. Table 18 presents the analyses of differences in seroresponse rates (the proportion achieving a ≥4-fold rise in ID50 from pre-second booster) against both the Original strain and Omicron BA.4/BA.5.

In subgroup analyses, neutralizing antibodies against a pseudovirus expressing the original SARS-CoV-2 Spike protein (D614G) and a pseudovirus expressing the Omicron BA.4/BA.5 Spike protein were similar in participants 65 years of age and older compared to participants 18 years through 64 years of age. The seroresponse rate observed at Day 29 was similar between age groups.

16 HOW SUPPLIED/STORAGE AND HANDLING

SPIKEVAX (2023-2024 Formula) is supplied as follows:

   NDC 80777-102-97     Carton of 10 multiple-dose vials, each vial containing 5 doses (each dose is 0.5 mL)   NDC 80777-102-95     Carton of 10 single dose vials, each vial containing 0.5 mL   NDC 80777-102-96     Carton of 10 single dose pre-filled syringes, each syringe containing 0.5 mL   NDC 80777-102-93     Carton of 10 single dose, blister-sealed pre-filled syringes, each syringe containing 0.5 mL

During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light.

Frozen Storage

Store frozen between -50°C to -15°C (-58°F to 5°F).

Storage of Multiple-Dose Vials after Thawing

Storage of Single Dose Vials after Thawing

Storage of Single Dose Pre-Filled Syringes after Thawing

Do not refreeze once thawed.

Thawed vials and syringes can be handled in room light conditions.

Transportation of Thawed Vials at 2°C to 8°C (36°F to 46°F)

Thawed vials can be transported at 2°C to 8°C (36°F to 46°F) for up to 12 hours in shipping containers qualified to maintain 2°C to 8°C (36°F to 46°F) and under routine road and air transport conditions with shaking and vibration minimized. Once thawed and transported at 2°C to 8°C (36°C to 46°F), vials should not be refrozen and should be stored at 2°C to 8°C (36°F to 46°F) until use.

Transportation of Thawed Syringes at 2°C to 8°C (36°F to 46°F)

Thawed pre-filled syringes can be transported at 2°C to 8°C (36°F to 46°F) in shipping containers qualified to maintain 2°C to 8°C (36°F to 46°F). Once thawed and transported at 2°C to 8°C (36°C to 46°F), pre-filled plastic syringes should not be refrozen and should be stored at 2°C to 8°C (36°F to 46°F) until use.

• •Storage at 2°C to 8°C (36°F to 46°F):oVials may be stored refrigerated between 2°C to 8°C (36°F to 46°F) for up to 30 days prior to first use.oVials should be discarded 12 hours after the first puncture.
• •Storage at 8°C to 25°C (46°F to 77°F):oVials may be stored between 8°C to 25°C (46°F to 77°F) for a total of 24 hours.oVials should be discarded 12 hours after the first puncture.oTotal storage at 8°C to 25°C (46°F to 77°F) must not exceed 24 hours.

17 PATIENT COUNSELING INFORMATION

Advise the vaccine recipient or caregiver to read the FDA-approved patient labeling.

Inform the vaccine recipient or caregiver of the potential benefits and risks of vaccination with SPIKEVAX.

Instruct the vaccine recipient or caregiver to report any adverse events to their healthcare provider or to the Vaccine Adverse Event Reporting System at 1-800-822-7967 and https://vaers.hhs.gov.

There is a pregnancy exposure registry for SPIKEVAX. Encourage individuals who receive SPIKEVAX around the time of conception or while pregnant to enroll in the pregnancy exposure registry. Pregnant individuals can enroll in the pregnancy exposure registry by calling 1-866-MODERNA (1-866-663-3762).

Manufactured for:Moderna US, Inc.Princeton, NJ 08540©2024 ModernaTX, Inc. All rights reserved.SPIKEVAX is a trademark of ModernaTX, Inc.Patent(s): www.modernatx.com/patents

US Govt. License No. 2256

Revised: 4/2024

Information for Recipients and CaregiversSPIKEVAX (pronounced SPĪK-văx)(COVID-19 Vaccine, mRNA) (2023-2024 Formula)

Please read this information sheet before getting SPIKEVAX. This summary is not intended to take the place of talking with your healthcare provider. If you have questions or would like more information, please talk with your healthcare provider.

What is SPIKEVAX?

SPIKEVAX is a vaccine to protect you against COVID-19. SPIKEVAX is for people 12 years of age and older. Vaccination with SPIKEVAX may not protect all people who receive the vaccine.

SPIKEVAX does not contain SARS-CoV-2, the virus that causes COVID-19. SPIKEVAX cannot give you COVID-19.

Who should not get SPIKEVAX?

You should not get SPIKEVAX if you had:

What should I tell my healthcare provider?

Tell your healthcare provider about all of your medical conditions, including if you:

How is SPIKEVAX given?

SPIKEVAX is given as an injection into the muscle.

What are the risks of SPIKEVAX?

Severe allergic reactions have occurred in some people who have received SPIKEVAX, Moderna COVID-19 Vaccine (Original monovalent), and Moderna COVID-19 Vaccine, Bivalent. There is a very small chance that SPIKEVAX could cause a severe allergic reaction. A severe allergic reaction would usually occur within a few minutes to 1 hour after getting a dose of SPIKEVAX. For this reason, your healthcare provider may ask you to stay for a short time at the place where you received your vaccine. Signs of a severe allergic reaction can include:

Myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the lining outside the heart) have occurred in some people who have received mRNA COVID-19 vaccines, including SPIKEVAX, Moderna COVID-19 Vaccine (Original monovalent), and Moderna COVID-19 Vaccine, Bivalent. Myocarditis and pericarditis following Moderna COVID-19 vaccines have occurred, most commonly in males 18 years through 24 years of age. In most of these individuals, symptoms began within a few days following vaccination. The chance of having this occur is very low. You should seek medical attention right away if you or your child has any of the following symptoms after receiving the vaccine, particularly during the 2 weeks after receiving a dose of the vaccine:

Side effects that have been reported in clinical trials with SPIKEVAX, Moderna COVID-19 Vaccine (Original monovalent), and Moderna COVID-19 Vaccine, Bivalent include:

Other side effects that have been reported include:

These may not be all of the possible side effects of SPIKEVAX. Ask your healthcare provider about any side effects that concern you. You may report side effects to the Vaccine Adverse Event Reporting System (VAERS) at 1-800-822-7967 or https://vaers.hhs.gov.

What if I am pregnant or breastfeeding?

If you are pregnant or breastfeeding, discuss your options with your healthcare provider.

A pregnancy exposure registry is available. You are encouraged to contact the registry as soon as you become aware of your pregnancy by calling 1-866-MODERNA (1-866-663-3762) or ask your healthcare provider to contact the registry for you.

What are the ingredients in SPIKEVAX?

SPIKEVAX contains the following ingredients:

SPIKEVAX does not contain preservatives.

If you would like more information, talk to your healthcare provider or visit www.spikevax.com or call 1-866-MODERNA (1-866-663-3762).

Manufactured for:Moderna US, Inc.Princeton, NJ 08540

©2023 ModernaTX, Inc. All rights reserved.SPIKEVAX is a trademark of ModernaTX, Inc.Patent(s): www.modernatx.com/patentsRevised: September 2023

• •a severe allergic reaction after a previous dose of SPIKEVAX, Moderna COVID-19 Vaccine (Original monovalent), or Moderna COVID-19 Vaccine, Bivalent SPIKEVAX is made the same way as the Moderna COVID-19 Vaccine (Original monovalent) and Moderna COVID-19 Vaccine, Bivalent, but it encodes the spike protein of SARS-CoV-2 Omicron variant lineage XBB.1.5 (Omicron XBB.1.5).
• •a severe allergic reaction to any ingredient of this vaccine (see What are the ingredients in SPIKEVAX?)

Package/Label Display Panel

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COVID-19 Vaccine, mRNA

Spikevax

2023-2024 Formula

Suspension for Intramuscular Injection

For 12 years and older

Multiple-Dose Vial

Each dose is 0.5 mL

Each vial contains 5 doses

NDC 80777-102-05

Package/Label Display Panel

NDC 80777-102-97

Moderna

COVID-19 Vaccine, mRNA

Spikevax

2023-2024 Formula

Suspension for Intramuscular Injection

For 12 years and older

Rx Only

Store frozen between -50°C to -15°C (-58°F to 5°F)

Protect from light

10 Multiple-Dose Vials

Each dose is 0.5 mL

Each vial contains 5 doses

Package/Label Display Panel

COVID-19 Vaccine, mRNA

Spikevax

2023-2024 Formula

For Intramuscular Use

For 12y and older

0.5 mL Single Dose Vial

Mfd. for: Moderna US, Inc.

NDC 80777-102-04

Rx Only

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NDC 80777-102-95

Moderna

COVID-19 Vaccine, mRNA

Spikevax

2023-2024 Formula

Suspension for Intramuscular Injection

For 12 years and older

Rx Only

Store frozen between -50°C to -15°C (-58°F to 5°F)

Protect from light

10 Single Dose Vials

Each dose is 0.5 mL

Package/Label Display Panel

COVID-19 Vaccine, mRNA

Spikevax

2023-2024 Formula

For 12 years and older

NDC 80777-102-01

0.5 mL Single Dose

Rx Only

For IM Use

Mfd. for: Moderna US, Inc.

Package/Label Display Panel

NDC 80777-102-96

Moderna

For 12 years and older

Rx Only

COVID-19 Vaccine, mRNA

Spikevax

2023-2024 Formula

Suspension for Intramuscular Injection

Store frozen between -50°C to -15°C (-58°F to 5°F)

Protect from light

10 Single Dose Pre-Filled Syringes

Each dose is 0.5 mL

Package/Label Display Panel

NDC 80777-102-93

Moderna

COVID-19 Vaccine, mRNA

Spikevax

2023-2024 Formula

Suspension for Intramuscular Injection

For 12 years and older

Rx Only

Store frozen between -50°C to -15°C (-58°F to 5°F)

Protect from light

10 Single Dose Pre-Filled Syringes

Each dose is 0.5 mL