MNEXSPIKE- covid-19 vaccine, mrna injection, suspension

mNEXSPIKE by

Drug Labeling and Warnings

mNEXSPIKE by is a Other medication manufactured, distributed, or labeled by Moderna US, Inc., ModernaTX, Inc., Rovi Pharma Industrial Services S.A., MODERNA BIOTECH SPAIN SL., Associates of Cape Cod, Eurofins Advantar Laboratories, LLC. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

  • 1 INDICATIONS AND USAGE

    MNEXSPIKE 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).

    MNEXSPIKE is approved for use in individuals who are:

    • 65 years of age and older, or
    • 12 years through 64 years of age with at least one underlying condition that puts them at high risk for severe outcomes from COVID-19.
  • 2 DOSAGE AND ADMINISTRATION

    For intramuscular use.

    2.1 Preparation for Administration

    • Verify that the label on the prefilled syringe states 2025-2026 Formula.
    • If prefilled syringes of MNEXSPIKE are frozen, thaw before use following the instructions below.
    Table 1: Thawing Conditions and Times

    Thaw in

    Refrigerator

    2°C to 8°C

    (36°F to 46°F)

    Thaw at

    Room Temperature

    15°C to 25°C

    (59°F to 77°F)

    Carton of 10 syringes

    Thaw for 2 hours and

    40 minutes

    Thaw for 1 hour and

    20 minutes

    Carton of 2 syringes

    Thaw for 1 hour and

    40 minutes

    Thaw for 40 minutes

    Carton of 1 syringe

    Thaw for 1 hour and

    40 minutes

    Thaw for 40 minutes

    One syringe (removed from carton)

    Thaw for 1 hour and

    40 minutes

    Thaw for 40 minutes
    • After thawing, do not refreeze.
    • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
    • MNEXSPIKE is a white to off-white suspension. It may contain white or translucent product-related particulates. Do not administer if vaccine is discolored or contains other particulate matter.
    • Do not shake.
    • With tip cap upright, remove tip cap by twisting counterclockwise until tip cap releases. Remove tip 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.
    • Discard after single use.

    2.2 Administration

    Administer MNEXSPIKE intramuscularly.

    2.3 Dosing and Schedule

    Administer MNEXSPIKE as a single 0.2 mL dose.

    For individuals previously vaccinated with any COVID-19 vaccine, administer the dose of MNEXSPIKE at least 3 months after the last dose of COVID-19 vaccine.

  • 3 DOSAGE FORMS AND STRENGTHS

    MNEXSPIKE is an injectable suspension.

    A single dose is 0.2 mL.

  • 4 CONTRAINDICATIONS

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

  • 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 MNEXSPIKE.

    5.2 Myocarditis and Pericarditis

    Analyses of postmarketing data from use of authorized or approved mRNA COVID-19 vaccines have demonstrated increased risks of myocarditis and pericarditis, with onset of symptoms typically in the first week following vaccination. The observed risk has been highest in males 12 years through 24 years of age.

    Based on analyses of commercial health insurance claims data from inpatient and outpatient settings, the estimated unadjusted incidence of myocarditis and/or pericarditis during the period 1 through 7 days following administration of the 2023-2024 Formula of mRNA COVID-19 vaccines was approximately 8 cases per million doses in individuals 6 months through 64 years of age and approximately 27 cases per million doses in males 12 years through 24 years of age.

    Although some individuals with myocarditis and/or pericarditis following administration of mRNA COVID-19 vaccines have required intensive care support, available data suggest that individuals typically have resolution of symptoms within a few days with conservative management.

    Follow-up information on cardiovascular outcomes in hospitalized patients who had been diagnosed with COVID-19 vaccine-associated myocarditis is available from a longitudinal retrospective observational study. Most of these patients had received a two-dose primary series of an mRNA COVID-19 vaccine prior to their diagnosis. In this study, at a median follow-up of approximately 5 months post-vaccination, persistence of abnormal cardiac magnetic resonance imaging (CMR) findings that are a marker for myocardial injury was common. The clinical and prognostic significance of these CMR findings is not known1 [see Adverse Reactions (6.2)].

    Information is not yet available about potential long-term sequelae of myocarditis or pericarditis following administration of mRNA COVID-19 vaccines.

    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 MNEXSPIKE [see Use in Specific Populations (8.6)].

    5.5 Limitations of Vaccine Effectiveness

    MNEXSPIKE may not protect all vaccine recipients.

  • 6 ADVERSE REACTIONS

    Most commonly (≥10%) reported adverse reactions following administration of MNEXSPIKE:

    • Participants 12 years through 17 years of age: pain at the injection site (up to 68.8%), headache (up to 54.5%), fatigue (up to 47.3%), myalgia (up to 39.2%), axillary swelling or tenderness (up to 34.6%), chills (up to 31.6%), arthralgia (up to 23.9%), and nausea/vomiting (up to 16.1%).
    • Participants 18 years through 64 years of age: pain at the injection site (up to 74.8%), fatigue (up to 54.3%), headache (up to 47.8%), myalgia (up to 41.6%), arthralgia (up to 32.4%), chills (up to 24.3%), axillary swelling or tenderness (up to 21.7%), and nausea/vomiting (up to 13.8%).
    • Participants 65 years of age and older: pain at the injection site (up to 54.6%), fatigue (up to 43.0%), headache (up to 33.1%), myalgia (up to 30.5%), arthralgia (up to 25.7%), chills (16.5%), nausea/vomiting (up to 11.4%), and axillary swelling or tenderness (up to 10.7%).

    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.

    Individuals 12 Years of Age and Older

    Single Dose (Bivalent Original and Omicron BA.4/BA.5) in Vaccine-Experienced

    The safety of MNEXSPIKE was evaluated in a randomized, observer-blind, active-controlled clinical trial conducted in the United States, United Kingdom, and Canada involving 11,417 participants 12 years of age and older who received a single dose of MNEXSPIKE (n=5,706) or comparator vaccine (Moderna COVID-19 Vaccine, Bivalent [Original and Omicron BA.4/BA.5] not U.S. licensed, authorized for emergency use; n=5,711) (Study 1, NCT05815498). MNEXSPIKE administered in the study contained 5 mcg mRNA encoding the membrane-bound, linked N-terminal domain (NTD) and receptor-binding domain (RBD) of the Spike (S) glycoprotein from SARS-CoV-2 Wuhan-Hu 1 strain (Original) and 5 mcg mRNA encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Omicron variant lineages BA.4 and BA.5. The comparator vaccine administered in the study contained 25 mcg mRNA encoding the S glycoprotein from SARS-CoV-2 Wuhan-Hu 1 strain (Original) and 25 mcg mRNA encoding the S glycoprotein from SARS-CoV-2 Omicron variant lineages BA.4 and BA.5. The median duration of follow-up for safety was 8.8 months.

    In Study 1, the median age of the population was 56 years (range 12 through 96 years); 8.7% of participants were 12 years through 17 years, 62.6% were 18 years through 64 years, and 28.7% were 65 years and older. Overall, 45.7% of the participants were male, 54.3% were female, 13.2% were Hispanic or Latino, 82.2% were White, 11.2% were Black or African American, 3.6% were Asian, 0.4% were American Indian or Alaska Native, 0.1% were Native Hawaiian or Pacific Islander, 0.4% were other races, and 1.5% were Multiracial. Overall, 64.3% of study participants reported at least one CDC-defined high-risk condition for severe COVID-19. Demographic characteristics were similar between participants who received MNEXSPIKE and those who received the comparator vaccine.

    All participants in the study, except one participant in the MNEXSPIKE group, had previously received at least one dose of a COVID-19 vaccine prior to the study with a median interval of 9.8 months since the last dose. Overall, 74.3% of participants (MNEXSPIKE=4,211; comparator vaccine=4,270) 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]).

    Solicited Adverse Reactions

    Local and systemic adverse reactions and use of antipyretic medication were solicited in an electronic diary for 7 days following injection (i.e., day of vaccination and the next 6 days) among participants who received MNEXSPIKE (n=5,702) and participants who received the comparator vaccine (n=5,706). Events that persisted for more than 7 days were followed until resolution.

    The reported number and percentage of solicited local and systemic adverse reactions for 12 years through 17 years are presented in Table 2 and Table 3, 18 years through 64 years are presented in Table 4 and Table 5, and 65 years and older are presented in Table 6 and Table 7, respectively.

    Table 2: Number and Percentage of Participants with Solicited Local Adverse Reactions Starting Within 7 Days* After Injection in Participants 12 Years Through 17 Years (Solicited Safety Set)

    * 7 days included day of vaccination and the subsequent 6 days. Events were collected in the electronic diary (e-diary).
    N=Number of participants in the Solicited Safety Set.
    n=Number of participants with listed solicited adverse reactions.
    a Absence of rows for Grade 3 or Grade 4 adverse reactions indicates no events were reported.
    b A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Original and Omicron variant lineages BA.4/BA.5
    c Moderna COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)
    d Pain and axillary swelling or tenderness grading scale: no interference with activity (Grade 1); some interference with activity (Grade 2); prevents daily activity (Grade 3).
    e Swelling and erythema grading scale: 25-50 mm / 2.5-5 cm (Grade 1); 51-100 mm / 5.1-10 cm (Grade 2); >100 mm / >10 cm (Grade 3).

    Local Adverse Reactionsa

    MNEXSPIKEb

    N=497

    n

    (%)

    Comparator Vaccinec

    N=495

    n

    (%)

    Paind

    342

    (68.8)

    390

    (78.8)

    Pain, Grade 3d

    10

    (2.0)

    19

    (3.8)

    Axillary swelling or tendernessd

    172

    (34.6)

    134

    (27.1)

    Axillary swelling or tenderness, Grade 3d

    6

    (1.2)

    2

    (0.4)

    Swelling (hardness) ≥25 mme

    18

    (3.6)

    25

    (5.1)

    Swelling (hardness) >100 mm, Grade 3e

    4

    (0.8)

    2

    (0.4)

    Erythema (redness) ≥25 mme

    6

    (1.2)

    13

    (2.6)
    Table 3: Number and Percentage of Participants with Solicited Systemic Adverse Reactions Starting Within 7 Days* After Injection in Participants 12 Years Through 17 Years (Solicited Safety Set)

    * 7 days included day of vaccination and the subsequent 6 days. Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary).
    N=Number of participants in the Solicited Safety Set.
    n=Number of participants with listed solicited adverse reactions.
    a No Grade 4 adverse reactions were reported.
    b A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Original and Omicron variant lineages BA.4/BA.5
    c Moderna COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)
    d Headache, fatigue, myalgia, arthralgia grading scale: no interference with activity (Grade 1); some interference with activity (Grade 2); prevents daily activity (Grade 3).
    e Chills grading scale: no interference with activity (Grade 1); some interference with activity not requiring medical intervention (Grade 2); prevents daily activity and requires medical intervention (Grade 3).
    f Nausea/vomiting grading scale: no interference with activity or 1-2 episodes/24 hours (Grade 1); some interference with activity or >2 episodes/24 hours (Grade 2); prevents daily activity, requires outpatient intravenous hydration (Grade 3).
    g Fever grading scale: ≥38.0° – ≤38.4°C / ≥100.4° – ≤101.1°F (Grade 1); ≥38.5° – ≤38.9°C / ≥101.2°– ≤102.0°F (Grade 2); ≥39.0° – ≤40.0°C / ≥102.1° – ≤104.0°F (Grade 3).

    Systemic Adverse Reactionsa

    MNEXSPIKEb

    N=497

    n

    (%)

    Comparator Vaccinec

    N=495

    n

    (%)

    Headached

    271

    (54.5)

    287

    (58.0)

    Headache, Grade 3d

    35

    (7.0)

    20

    (4.0)

    Fatigued

    235

    (47.3)

    251

    (50.7)

    Fatigue, Grade 3d

    34

    (6.8)

    22

    (4.4)

    Myalgiad

    195

    (39.2)

    178

    (36.0)

    Myalgia, Grade 3d

    28

    (5.6)

    17

    (3.4)

    Chillse

    157

    (31.6)

    158

    (31.9)

    Chills, Grade 3e

    6

    (1.2)

    1

    (0.2)

    Arthralgiad

    119

    (23.9)

    117

    (23.6)

    Arthralgia, Grade 3d

    10

    (2.0)

    6

    (1.2)

    Nausea/vomitingf

    80

    (16.1)

    87

    (17.6)

    Nausea/vomiting, Grade 3f

    0

    (0)

    2

    (0.4)

    Feverg

    49

    (9.9)

    46

    (9.3)

    Fever, Grade 3g

    4

    (0.8)

    2

    (0.4)

    Use of antipyretic or pain medication

    186

    (37.4)

    211

    (42.6)
    Table 4: Number and Percentage of Participants with Solicited Local Adverse Reactions Starting Within 7 Days* After Injection in Participants 18 Years Through 64 Years (Solicited Safety Set)

    * 7 days included day of vaccination and the subsequent 6 days. Events were collected in the electronic diary (e-diary).
    N=Number of participants in the Solicited Safety Set.
    n=Number of participants with listed solicited adverse reactions.
    a No Grade 4 adverse reactions were reported.
    b A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Original and Omicron variant lineages BA.4/BA.5
    c Moderna COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)
    d Pain and axillary swelling or tenderness grading scale: no interference with activity (Grade 1); some interference with activity (Grade 2); prevents daily activity (Grade 3).
    e Swelling and erythema grading scale: 25-50 mm / 2.5-5 cm (Grade 1); 51-100 mm / 5.1-10 cm (Grade 2); >100 mm / >10 cm (Grade 3).

    Local Adverse Reactionsa

    MNEXSPIKEb

    N=3,573

    n

    (%)

    Comparator Vaccinec

    N=3,574

    n

    (%)

    Paind

    2,672

    (74.8)

    2,920

    (81.7)

    Pain, Grade 3d

    38

    (1.1)

    49

    (1.4)

    Axillary swelling or tendernessd

    777

    (21.7)

    749

    (21.0)

    Axillary swelling or tenderness, Grade 3d

    11

    (0.3)

    15

    (0.4)

    Swelling (hardness) ≥25 mme

    140

    (3.9)

    246

    (6.9)

    Swelling (hardness) >100 mm, Grade 3e

    11

    (0.3)

    19

    (0.5)

    Erythema (redness) ≥25 mme

    85

    (2.4)

    152

    (4.3)

    Erythema (redness) >100 mm, Grade 3e

    9

    (0.3)

    17

    (0.5)
    Table 5: Number and Percentage of Participants with Solicited Systemic Adverse Reactions Starting Within 7 Days* After Injection in Participants 18 Years Through 64 Years (Solicited Safety Set)

    * 7 days included day of vaccination and the subsequent 6 days. Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary).
    N=Number of participants in the Solicited Safety Set.
    n=Number of participants with listed solicited adverse reactions.
    a No Grade 4 adverse reactions were reported.
    b A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Original and Omicron variant lineages BA.4/BA.5
    c Moderna COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)
    d Fatigue, headache, myalgia, arthralgia grading scale: no interference with activity (Grade 1); some interference with activity (Grade 2); prevents daily activity (Grade 3).
    e Chills grading scale: no interference with activity (Grade 1); some interference with activity not requiring medical intervention (Grade 2); prevents daily activity and requires medical intervention (Grade 3).
    f Nausea/vomiting grading scale: no interference with activity or 1-2 episodes/24 hours (Grade 1); some interference with activity or >2 episodes/24 hours (Grade 2); prevents daily activity, requires outpatient intravenous hydration (Grade 3).
    g Fever grading scale: ≥38.0° – ≤38.4°C / ≥100.4° – ≤101.1°F (Grade 1); ≥38.5° – ≤38.9°C / ≥101.2°– ≤102.0°F (Grade 2); ≥39.0° – ≤40.0°C / ≥102.1° – ≤104.0°F (Grade 3).

    Systemic Adverse Reactionsa

    MNEXSPIKEb

    N=3,573

    n

    (%)

    Comparator Vaccinec

    N=3,574

    n

    (%)

    Fatigued

    1,939

    (54.3)

    1,876

    (52.5)

    Fatigue, Grade 3d

    170

    (4.8)

    156

    (4.4)

    Headached

    1,708

    (47.8)

    1,583

    (44.3)

    Headache, Grade 3d

    90

    (2.5)

    76

    (2.1)

    Myalgiad

    1,485

    (41.6)

    1,469

    (41.1)

    Myalgia, Grade 3d

    144

    (4.0)

    105

    (2.9)

    Arthralgiad

    1,159

    (32.4)

    1,094

    (30.6)

    Arthralgia, Grade 3d

    86

    (2.4)

    62

    (1.7)

    Chillse

    867

    (24.3)

    760

    (21.3)

    Chills, Grade 3e

    26

    (0.7)

    22

    (0.6)

    Nausea/vomitingf

    492

    (13.8)

    424

    (11.9)

    Nausea/vomiting, Grade 3f

    4

    (0.1)

    3

    (<0.1)

    Feverg

    193

    (5.4)

    138

    (3.9)

    Fever, Grade 3g

    27

    (0.8)

    17

    (0.5)

    Use of antipyretic or pain medication

    1,243

    (34.8)

    1,226

    (34.3)
    Table 6: Number and Percentage of Participants with Solicited Local Adverse Reactions Starting Within 7 Days* After Injection in Participants 65 Years and Older (Solicited Safety Set)

    * 7 days included day of vaccination and the subsequent 6 days. Events were collected in the electronic diary (e-diary).
    N=Number of participants in the Solicited Safety Set.
    n=Number of participants with listed solicited adverse reactions.
    a No Grade 4 adverse reactions were reported.
    b A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Original and Omicron variant lineages BA.4/BA.5
    c Moderna COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)
    d Pain and axillary swelling or tenderness grading scale: no interference with activity (Grade 1); some interference with activity (Grade 2); prevents daily activity (Grade 3).
    e Swelling and erythema grading scale: 25-50 mm / 2.5-5 cm (Grade 1); 51-100 mm / 5.1-10 cm (Grade 2); >100 mm / >10 cm (Grade 3).

    Local Adverse Reactionsa

    MNEXSPIKEb

    N=1,632

    n

    (%)

    Comparator Vaccinec

    N=1,637

    n

    (%)

    Paind

    891

    (54.6)

    1,109

    (67.7)

    Pain, Grade 3d

    12

    (0.7)

    7

    (0.4)

    Axillary swelling or tendernessd

    174

    (10.7)

    164

    (10.0)

    Axillary swelling or tenderness, Grade 3d

    2

    (0.1)

    2

    (0.1)

    Swelling (hardness) ≥25 mme

    48

    (2.9)

    88

    (5.4)

    Swelling (hardness), Grade 3e

    1

    (<0.1)

    11

    (0.7)

    Erythema (redness) ≥25 mme

    32

    (2.0)

    60

    (3.7)

    Erythema (redness), Grade 3e

    2

    (0.1)

    7

    (0.4)
    Table 7: Number and Percentage of Participants with Solicited Systemic Adverse Reactions Starting Within 7 Days* After Injection in Participants 65 Years and Older (Solicited Safety Set)

    * 7 days included day of vaccination and the subsequent 6 days. Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary).
    N=Number of participants in the Solicited Safety Set.
    n=Number of participants with listed solicited adverse reactions.
    a Absence of rows for Grade 4 adverse reactions indicates no events were reported.
    b A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Original and Omicron variant lineages BA.4/BA.5
    c Moderna COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)
    d Headache, fatigue, myalgia, arthralgia grading scale: no interference with activity (Grade 1); some interference with activity (Grade 2); prevents daily activity (Grade 3).
    e Chills grading scale: no interference with activity (Grade 1); some interference with activity not requiring medical intervention (Grade 2); prevents daily activity and requires medical intervention (Grade 3).
    f Nausea/vomiting grading scale: no interference with activity or 1-2 episodes/24 hours (Grade 1); some interference with activity or >2 episodes/24 hours (Grade 2); prevents daily activity, requires outpatient intravenous hydration (Grade 3).
    g Fever grading scale: ≥38.0° – ≤38.4°C / ≥100.4° – ≤101.1°F (Grade 1); ≥38.5° – ≤38.9°C / ≥101.2°– ≤102.0°F (Grade 2); ≥39.0° – ≤40.0°C / ≥102.1° – ≤104.0°F (Grade 3); >40.0°C / >104.0°F (Grade 4).

    Systemic Adverse Reactionsa

    MNEXSPIKEb

    N=1,632

    n

    (%)

    Comparator Vaccinec

    N=1,637

    n

    (%)

    Fatigued

    702

    (43.0)

    671

    (41.0)

    Fatigue, Grade 3d

    59

    (3.6)

    41

    (2.5)

    Headached

    540

    (33.1)

    479

    (29.3)

    Headache, Grade 3d

    22

    (1.3)

    22

    (1.3)

    Myalgiad

    498

    (30.5)

    467

    (28.5)

    Myalgia, Grade 3d

    33

    (2.0)

    27

    (1.6)

    Arthralgiad

    418

    (25.6)

    366

    (22.4)

    Arthralgia, Grade 3d

    24

    (1.5)

    21

    (1.3)

    Chillse

    269

    (16.5)

    209

    (12.8)

    Chills, Grade 3e

    10

    (0.6)

    8

    (0.5)

    Nausea/vomitingf

    119

    (7.3)

    114

    (7.0)

    Nausea/vomiting, Grade 3f

    2

    (0.1)

    5

    (0.3)

    Feverg

    75

    (4.6)

    70

    (4.3)

    Fever, Grade 3g

    2

    (0.1)

    9

    (0.6)

    Fever, Grade 4g

    0

    (0)

    1

    (<0.1)

    Use of antipyretic or pain medication

    429

    (26.3)

    393

    (24.0)

    Solicited local and systemic adverse reactions reported following vaccine administration had a median duration of 2 days for MNEXSPIKE and 2 to 3 days for the comparator vaccine.

    Unsolicited Adverse Events

    Participants were monitored for unsolicited adverse events for 28 days following injection. Serious adverse events and medically attended adverse events will be recorded for the entire study duration (1 year). Among the 11,417 participants who received MNEXSPIKE (n=5,706) or the comparator vaccine (n=5,711), unsolicited adverse events that occurred within 28 days following injection were reported by 12.3% of participants (n=701) who received MNEXSPIKE and 11.9% of participants (n=680) who received the comparator vaccine.

    There were no notable patterns or numerical imbalances between treatment groups for specific categories of adverse events that would suggest a causal relationship to MNEXSPIKE.

    Serious Adverse Events

    Serious adverse events were reported by 2.7% of participants (n=156) who received MNEXSPIKE and 2.6% of participants (n=151) who received the comparator vaccine through a median follow-up of 8.8 months. There were no serious adverse events considered causally related to MNEXSPIKE.

    There were no notable patterns or imbalances between treatment groups for specific categories of serious adverse events that would suggest a causal relationship to MNEXSPIKE.

    Single Dose (Monovalent Omicron XBB.1.5) in Vaccine-Experienced

    The safety of MNEXSPIKE was evaluated in a randomized, observer-blind, active-controlled clinical trial conducted in Japan involving 689 participants 12 years of age and older who received a single dose of MNEXSPIKE (n=343) or comparator vaccine (SPIKEVAX 2023-2024 Formula [n=346]) (Study 2). MNEXSPIKE administered in the study contained 10 mcg mRNA encoding the membrane-bound, linked N-terminal domain (NTD) and receptor-binding domain (RBD) of the Spike (S) glycoprotein from SARS-CoV-2 Omicron variant lineage XBB.1.5. The comparator vaccine administered in the study contained 50 mcg mRNA encoding the S glycoprotein from SARS-CoV-2 Omicron variant lineage XBB.1.5. The median duration of follow-up for safety was 35 days.

    In Study 2, the median age of the population was 52 years (range 12 through 83 years); 20.3% of participants were 12 years through 17 years, 58.8% were 18 years through 64 years, and 20.9% were 65 years of age and older. Overall, 65.7% were male, 34.3% were female, and all participants were Asian. All participants in the study had previously received at least one dose of a COVID-19 vaccine prior to the study with a median interval of 16.7 months since the last dose.

    Participants were monitored for unsolicited adverse events for 28 days following injection. Among the 689 participants who received MNEXSPIKE (n=343) or the comparator vaccine (n=346), unsolicited adverse events that occurred within 28 days following injection were reported by 7.0% of participants (n=24) who received MNEXSPIKE and 6.9% of participants (n=24) who received the comparator vaccine. There were no notable patterns or numerical imbalances between treatment groups for specific categories of adverse events that would suggest a causal relationship to MNEXSPIKE. No serious adverse events were reported.

    In addition, in a separate portion of Study 1, vaccine-experienced participants 12 years of age and older (n=617), including 53 participants 65 years of age and older, received a single dose of MNEXSPIKE (Monovalent Omicron XBB.1.5). Participants were monitored for serious adverse events through 6 months following injection. There were no serious adverse events considered causally related to MNEXSPIKE.

    Single Dose (Monovalent Omicron XBB.1.5) in Vaccine-Naïve

    In a separate randomized, observer-blind, active-controlled portion of Study 1 conducted in the United States, 782 COVID-19 vaccine-naïve participants 12 years of age and older received a single dose of MNEXSPIKE (n=396) or comparator vaccine (SPIKEVAX 2023-2024 Formula [n=386]). The vaccine formula of MNEXSPIKE administered in the study contained 10 mcg mRNA encoding the membrane-bound, linked N-terminal domain (NTD) and receptor-binding domain (RBD) of the Spike (S) glycoprotein from SARS-CoV-2 Omicron variant lineage XBB.1.5. The comparator vaccine administered in the study contained 50 mcg mRNA encoding the S glycoprotein from SARS-CoV-2 Omicron variant lineage XBB.1.5. The median duration of follow-up for safety was 5.8 months.

    Among vaccine-naïve participants in this study, the median age was 38 years (range 12 through 81 years); 12.4% of participants were 12 years through 17 years, 79.4% were 18 years through 64 years, and 8.2% were 65 years and older. Overall, 46.9% of the participants were male, 53.1% were female, 36.6% were Hispanic or Latino, 53.5% were White, 42.8% were Black or African American, 0.1% were Asian, 0.9% were American Indian or Alaska Native, 0.3% were other races, and 1.5% were Multiracial. Demographic characteristics were similar between participants who received MNEXSPIKE and those who received the comparator vaccine.

    Solicited Adverse Reactions

    Local and systemic adverse reactions and use of antipyretic medication were solicited in an electronic diary for 7 days following injection (i.e., day of vaccination and the next 6 days) among participants who received MNEXSPIKE (n=396) and participants who received the comparator vaccine (n=386). Events that persisted for more than 7 days were followed until resolution.

    The reported number and percentage of solicited local and systemic adverse reactions for vaccine-naïve participants 12 years of age and older are presented in Table 8 and Table 9.

    Table 8: Number and Percentage of Participants with Solicited Local Adverse Reactions Starting Within 7 Days* After Injection in Participants 12 Years and Older (Solicited Safety Set)

    * 7 days included day of vaccination and the subsequent 6 days. Events were collected in the electronic diary (e-diary).
    N=Number of participants in the Solicited Safety Set.
    n=Number of participants with listed solicited adverse reactions.
    a No Grade 4 adverse reactions were reported.
    b A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Omicron variant lineage XBB.1.5
    c SPIKEVAX 2023-2024 Formula
    d Pain and axillary swelling or tenderness grading scale: no interference with activity (Grade 1); some interference with activity (Grade 2); prevents daily activity (Grade 3).
    e Swelling and erythema grading scale: 25-50 mm / 2.5-5 cm (Grade 1); 51-100 mm / 5.1-10 cm (Grade 2); >100 mm / >10 cm (Grade 3).

    Local Adverse Reactionsa

    MNEXSPIKEb

    N=396

    n

    (%)

    Comparator Vaccinec

    N=386

    n

    (%)

    Paind

    145

    (36.6)

    183

    (47.4)

    Pain, Grade 3d

    7

    (1.8)

    9

    (2.3)

    Axillary swelling or tendernessd

    69

    (17.4)

    79

    (20.5)

    Axillary swelling or tenderness, Grade 3d

    2

    (0.5)

    4

    (1.0)

    Swelling (hardness) ≥25 mme

    6

    (1.5)

    13

    (3.4)

    Swelling (hardness) >100 mm, Grade 3e

    2

    (0.5)

    3

    (0.8)

    Erythema (redness) ≥25 mme

    5

    (1.3)

    9

    (2.3)

    Erythema (redness) ≥100 mm, Grade 3e

    3

    (0.8)

    3

    (0.8)
    Table 9: Number and Percentage of Participants with Solicited Systemic Adverse Reactions Starting Within 7 Days* After Injection in Participants 12 Years and Older (Solicited Safety Set)

    * 7 days included day of vaccination and the subsequent 6 days. Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary).
    N=Number of participants in the Solicited Safety Set.
    n=Number of participants with listed solicited adverse reactions.
    a No Grade 4 adverse reactions were reported.
    b A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Omicron variant lineage XBB.1.5
    c SPIKEVAX 2023-2024 Formula
    d Headache, fatigue, myalgia, arthralgia grading scale: no interference with activity (Grade 1); some interference with activity (Grade 2); prevents daily activity (Grade 3).
    e Chills grading scale: no interference with activity (Grade 1); some interference with activity not requiring medical intervention (Grade 2); prevents daily activity and requires medical intervention (Grade 3).
    f Nausea/vomiting grading scale: no interference with activity or 1-2 episodes/24 hours (Grade 1); some interference with activity or >2 episodes/24 hours (Grade 2); prevents daily activity, requires outpatient intravenous hydration (Grade 3).
    g Fever grading scale: ≥38.0° – ≤38.4°C / ≥100.4° – ≤101.1°F (Grade 1); ≥38.5° – ≤38.9°C / ≥101.2°– ≤102.0°F (Grade 2); ≥39.0° – ≤40.0°C / ≥102.1° – ≤104.0°F (Grade 3).

    Systemic Adverse Reactionsa

    MNEXSPIKEb

    N=396

    n

    (%)

    Comparator Vaccinec

    N=386

    n

    (%)

    Headached

    119

    (30.1)

    104

    (26.9)

    Headache, Grade 3d

    7

    (1.8)

    4

    (1.0)

    Fatigued

    110

    (27.8)

    98

    (25.4)

    Fatigue, Grade 3d

    10

    (2.5)

    4

    (1.0)

    Myalgiad

    99

    (25.0)

    101

    (26.2)

    Myalgia, Grade 3d

    10

    (2.5)

    9

    (2.3)

    Arthralgiad

    82

    (20.7)

    82

    (21.2)

    Arthralgia, Grade 3d

    6

    (1.5)

    6

    (1.6)

    Chillse

    58

    (14.6)

    63

    (16.3)

    Chills, Grade 3e

    4

    (1.0)

    0

    (0)

    Nausea/vomitingf

    52

    (13.1)

    49

    (12.7)

    Nausea/vomiting, Grade 3f

    2

    (0.5)

    1

    (0.3)

    Feverg

    15

    (3.8)

    11

    (2.8)

    Fever, Grade 3g

    4

    (1.0)

    4

    (1.0)

    Use of antipyretic or pain medication

    84

    (21.2)

    56

    (14.5)

    Solicited local and systemic adverse reactions reported following vaccine administration had a median duration of 2 to 3 days for both MNEXSPIKE and the comparator vaccine. In analyses of solicited adverse reactions by age groups in vaccine-naïve participants 12 years through 17 years of age (n=51), 18 years through 64 years of age (n=310), and 65 years of age and older (n=35) who received MNEXSPIKE, the most commonly occurring solicited adverse reactions (≥10%) were reported in a similar or lower percentage of participants compared with those reported in the respective age groups in MNEXSPIKE vaccine-experienced participants (refer to Tables 2 through 7), with the exception of nausea/vomiting reported in 11.4% of vaccine-naïve participants 65 years of age and older who received MNEXSPIKE.

    Unsolicited Adverse Events

    Participants were monitored for unsolicited adverse events for 28 days following injection. Serious adverse events and medically attended adverse events were recorded for the entire study duration (6 months). Among the 782 vaccine-naïve participants who received MNEXSPIKE (n=396) or the comparator vaccine (n=386), unsolicited adverse events that occurred within 28 days following injection were reported by 4.3% of participants (n=17) who received MNEXSPIKE and 6.2% of participants (n=24) who received the comparator vaccine.

    There were no notable patterns or numerical imbalances between treatment groups for specific categories of adverse events that would suggest a causal relationship to MNEXSPIKE.

    Serious Adverse Events

    Serious adverse events were reported by 1.5% of vaccine-naïve participants (n=6) who received MNEXSPIKE and 3.1% of vaccine-naïve participants (n=12) who received the comparator vaccine through a median follow-up of 5.8 months. There were no serious adverse events considered causally related to MNEXSPIKE.

    There were no notable patterns or imbalances between treatment groups for specific categories of serious adverse events that would suggest a causal relationship to MNEXSPIKE.

    6.2 Postmarketing Experience

    Postmarketing data with authorized or approved mRNA COVID-19 vaccines have demonstrated increased risks of myocarditis and pericarditis [see Warnings and Precautions (5.2)].

    Cardiovascular Outcomes in Patients Diagnosed with mRNA COVID-19 Vaccine-associated Myocarditis

    In a longitudinal retrospective observational cohort study across 38 hospitals in the U.S., information on cardiovascular outcomes was collected on 333 patients 5 years through 29 years of age who had been diagnosed with COVID-19 vaccine-associated myocarditis. Among these patients, 322 were confirmed to have received an mRNA COVID-19 vaccine encoding the S glycoprotein of the Original SARS-CoV-2. Of 331 patients, 278 had onset of symptoms following the second dose of a primary series, 33 following the first dose of a primary series, and 20 following a first booster dose1.

    Among 307 patients who had been diagnosed with COVID-19 vaccine-associated myocarditis for whom follow-up information was available, 89 reported cardiac symptoms at a median follow-up of 91 days (interquartile range 25-186 days) post-vaccination1.

    Initial gadolinium-enhanced cardiac magnetic resonance imaging (CMR) was performed on 216 patients, of whom 177 had late gadolinium enhancement (LGE), a marker of myocardial injury. Among 161 patients who had LGE on initial CMR and who had a follow-up gadolinium-enhanced CMR at a median follow-up of 159 days (interquartile range 78-253 days), 98 had persistence of LGE. Overall, the severity of LGE decreased during follow-up. The clinical and prognostic significance of these CMR findings is not known1.

    Limitations of this study include potential selection bias towards patients with more severe myocarditis who are more likely to be hospitalized and have CMR, variability in diagnostic testing, and variability in follow-up1.

  • 8 USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy

    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 MNEXSPIKE administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

    A developmental toxicity study was performed where female rats were administered a vaccine formulation containing 80 mcg of nucleoside-modified messenger ribonucleic acid (mRNA) (which is 8 times the amount of nucleoside-modified mRNA in a full human dose of MNEXSPIKE [encoding the N-terminal domain (NTD) and receptor-binding domain (RBD) of the spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu 1 strain]) twice prior to mating and twice during gestation. The study revealed no evidence of harm to the fetus due to the vaccine. The study also revealed no evidence of effects on female fertility (see Animal Data).

    Data

    Animal Data

    A developmental toxicity study was conducted to assess the effects of MNEXSPIKE on pregnant/lactating female rats, as well as the development of the embryo/fetus and offspring following exposure to the female to the vaccine from implantation through the end of pregnancy, with follow-up of the offspring through weaning. In this study, 0.2 mL of a vaccine formulation containing 80 mcg of nucleoside-modified mRNA per dose (which is 8 times the amount of mRNA in a full human dose of MNEXSPIKE [10 mcg of nucleoside-modified mRNA; encoding the N-terminal domain (NTD) and receptor-binding domain (RBD) of the spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu 1 strain]). Each dose of the vaccine formulation administered to rats also contained the following ingredients: a total lipid content of 1.8 mg (SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC]), 0.48 mg tromethamine, 17 mg sucrose, and 0.1 mg sodium acetate). MNEXSPIKE 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. The study also revealed no evidence of effects on female fertility.

    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 MNEXSPIKE is excreted in human milk. Data are not available to assess the effects of MNEXSPIKE 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 MNEXSPIKE and any potential adverse effects on the breastfed infant from MNEXSPIKE 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 MNEXSPIKE in individuals 12 years through 17 years of age with at least one underlying condition that puts them at high risk for severe outcomes from COVID-19 is based on safety and effectiveness data in this age group and in adults [see Adverse Reactions (6) and Clinical Studies (14)]. The safety and effectiveness of MNEXSPIKE have not been established in individuals younger than 12 years of age.

    8.5 Geriatric Use

    Clinical studies of MNEXSPIKE included approximately 1,801 participants 65 years of age and older and 348 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 with participants 18 years through 64 years of age [see Adverse Reactions (6.1)].

    Relative vaccine efficacy was similar among participants 65 years of age and older and participants 18 years through 64 years [see Clinical Studies (14)].

    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

    MNEXSPIKE (COVID-19 Vaccine, mRNA) is a sterile white to off-white injectable suspension for intramuscular use.

    Each 0.2 mL dose of MNEXSPIKE (2025-2026 Formula) contains 10 mcg nucleoside-modified messenger RNA (mRNA) encoding the N-terminal domain (NTD) and receptor-binding domain (RBD) of the Spike glycoprotein of the SARS-CoV-2 Omicron variant sublineage LP.8.1. Each dose also contains the following ingredients: a total lipid content of 0.2 mg (SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC]), 0.09 mg tromethamine, 0.51 mg tromethamine hydrochloride, and 17 mg sucrose.

    MNEXSPIKE does not contain a preservative.

    The 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 MNEXSPIKE is formulated in lipid particles, which enable delivery of the nucleoside-modified mRNA into host cells to allow expression of the N-terminal domain (NTD) and receptor-binding domain (RBD) of the Spike (S) glycoprotein of SARS-CoV-2. The vaccine elicits an immune response which protects against COVID-19.

  • 13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    MNEXSPIKE has not been evaluated for the potential to cause carcinogenicity, genotoxicity, or impairment of male fertility in animals. [see Use in Specific Populations (8.1)].

  • 14 CLINICAL STUDIES

    14.1 Adults and Adolescents 12 Years of Age and Older

    Efficacy and Immunogenicity of Single Dose (Bivalent Original and Omicron BA.4/BA.5) in Vaccine-Experienced

    Study 1 is a Phase 3 randomized, observer-blind, active-controlled clinical trial that evaluated the relative vaccine efficacy, safety, and immunogenicity of MNEXSPIKE in participants 12 years of age and older in the United States, United Kingdom, and Canada. Randomization was stratified by age: 12 years through 17 years, 18 years through 64 years, and 65 years of age and older. 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 2 months before enrollment, as well as participants with stable human immunodeficiency virus (HIV) infection. A total of 11,454 participants were randomized in a 1:1 ratio to receive MNEXSPIKE (n=5,728), a vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Original and Omicron variant lineages BA.4/BA.5, or comparator vaccine (Moderna COVID-19 Vaccine, Bivalent [Original and Omicron BA.4/BA.5] not U.S. licensed, authorized for emergency use; n=5,726). All participants in the study, except one participant in the MNEXSPIKE group, had previously received at least one dose of a COVID-19 vaccine prior to the study with a median interval of 9.8 months since the last dose.

    The primary efficacy analysis population (referred to as the Per-Protocol Set for Efficacy) included 11,366 participants who received either MNEXSPIKE (n=5,679) or Moderna COVID-19 Vaccine, Bivalent (n=5,687). In the Per-Protocol Set for Efficacy, 45.7% of participants were male, 54.3% were female, 13.1% were Hispanic or Latino, 82.2% were White, 11.1% were Black or African American, 3.6% were Asian, 0.4% were American Indian or Alaska Native, 0.1% were Native Hawaiian or Pacific Islander, 0.3% were other races, and 1.5% were Multiracial. The median age of participants was 56 years (range 12 through 96 years) and 28.7% of participants were 65 years of age and older. There were no notable differences in demographics between participants who received MNEXSPIKE and those who received the comparator vaccine.

    The population for the relative vaccine efficacy analysis included participants 12 years of age and older who were enrolled from March 28, 2023, and followed for the development of COVID-19 through January 31, 2024. The median length of follow-up was 8 months.

    The primary efficacy objective in this study was to demonstrate the noninferior vaccine efficacy against COVID-19 starting 14 days after MNEXSPIKE compared with that after the comparator vaccine. The case definition of COVID-19 was the presence of at least one symptom from a list of COVID-19 symptoms and a positive NP swab for SARS-CoV-2 by RT-PCR. Listed symptoms were fever (temperature ≥38°C / ≥100.4°F) or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle aches or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, and diarrhea. The statistical criterion to demonstrate noninferiority (lower bound of the 99.4% CI >-10%) for relative vaccine efficacy was met (Table 10).

    Table 10: Relative Vaccine Efficacy Against COVID-19* in Participants 12 Years of Age and Older† Starting 14 Days After a Single Dose of MNEXSPIKE or Comparator Vaccine – Per-Protocol Set for Efficacy

    * Presence of at least one symptom from a list of COVID-19 symptoms and a positive NP swab for SARS-CoV-2 by RT-PCR. Listed symptoms were fever (temperature ≥38°C / ≥100.4°F) or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle aches or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, and diarrhea.
    † Participants had previously received at least one dose of a COVID-19 vaccine prior to the study.
    a A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Original and Omicron variant lineages BA.4/BA.5
    b Moderna COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)
    c Person-months is defined as the total months from study injection date to the date of event (COVID-19), date of off-study COVID-19 vaccine, last date of study participation, death date or efficacy data cutoff date, whichever is the earliest.
    d Relative Vaccine Efficacy (rVE) = 1-hazard ratio (MNEXSPIKE vs comparator vaccine). Hazard ratio and CI are estimated using a stratified Cox proportional hazard model (stratified by age group per randomization) with Efron's method of tie handling and with the treatment group as a fixed effect. Alpha-adjusted 2-sided (99.4%) confidence level is calculated using Lan-DeMets O’Brien-Fleming spending function (nominal one-sided alpha = 0.0028).
    e The success criterion for the primary efficacy endpoint was that the lower limit of the 2-sided CI for rVE was >-10%.

    MNEXSPIKEa

    Comparator Vaccineb

    Relative Vaccine Efficacy

    (99.4% CI)d

     

    Participants

    (N)

     

    COVID-19

    Cases

    (n)

     

    Incidence Rate of COVID-19 Per 100 Person-Monthsc

     

    Participants

    (N)

     

    COVID-19

    Cases

    (n)

     

    Incidence Rate of COVID-19 Per 100 Person-Monthsc

     

    5,679

    560

    1.4

    5,687

    617

    1.5

    9.3%

    (-6.6%, 22.8%)e

    A descriptive analysis of incidence of COVID-19 in participants 12 years of age and older by age subgroup was conducted (Table 11).

    Table 11: Descriptive Analysis of Incidence of COVID-19* in Participants 12 Years of Age and Older† by Age Subgroup Starting 14 Days After a Single Dose of MNEXSPIKE or Comparator Vaccine – Per-Protocol Set for Efficacy

    * Presence of at least one symptom from a list of COVID-19 symptoms and a positive NP swab for SARS-CoV-2 by RT-PCR. Listed symptoms were fever (temperature ≥38°C / ≥100.4°F) or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle aches or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, and diarrhea.
    † Participants had previously received at least one dose of a COVID-19 vaccine prior to the study.  
    a A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Original and Omicron variant lineages BA.4/BA.5
    b Moderna COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)
    c Person-months is defined as the total months from study injection date to the date of event (COVID-19), date of off-study COVID-19 vaccine, last date of study participation, death date or efficacy data cutoff date, whichever is the earliest.
    d rVE=relative vaccine efficacy
    e Descriptive relative vaccine efficacy means that these endpoints were not hypothesis-tested and do not necessarily make valid inferences about vaccine efficacy.
    f VE cannot be reliably estimated due to the low number of cases accrued in this age group.

    Age Subgroup

    (Years)

     

    MNEXSPIKEa

    Comparator Vaccineb

    Descriptive rVEd

    (95% CI)e

     

    Participants

    (N)

     

    COVID-19

    Cases

    (n)

     

    Incidence Rate of COVID-19

    Per 100 Person-Monthsc

     

    Participants

    (N)

     

    COVID-19

    Cases

    (n)

     

    Incidence Rate of COVID-19

    Per 100 Person-Monthsc

     

    12 to <18

    491

    29

    1.0

    490

    23

    0.8

    -29.2%f

    (-123.3%, 25.3%)

    18 to <65

    3,558

    382

    1.4

    3,562

    422

    1.6

    9.7%

    (-3.8%, 21.3%)

    ≥65

    1,630

    149

    1.3

    1,635

    172

    1.5

    13.5%

    (-7.7%, 30.6%)

    In Study 1, 60.8% of participants 12 years through 64 years of age reported at least one CDC-defined high-risk condition for severe COVID-19. The type and frequency of high-risk conditions reported in participants were generally representative of high-risk conditions in the U.S. general population 12 years through 64 years of age. A descriptive analysis of the incidence of COVID-19 in participants 12 years through 64 years of age with at least one CDC-defined high-risk condition for severe COVID-19 after a single dose of MNEXSPIKE or the comparator vaccine is presented in Table 12. In this analysis, 7.2% of participants were 12 years through 17 years of age and the remaining 92.8% of participants were 18 years through 64 years of age.

    Table 12: Descriptive Analysis of Incidence of COVID-19* in Participants 12 Years Through 64 Years of Age† with at Least One CDC-Defined High-Risk Condition for Severe COVID-19‡ Starting 14 Days After a Single Dose of MNEXSPIKE or Comparator Vaccine – Per-Protocol Set for Efficacy

    * Presence of at least one symptom from a list of COVID-19 symptoms and a positive NP swab for SARS-CoV-2 by RT-PCR. Listed symptoms were fever (temperature ≥38°C / ≥100.4°F) or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle aches or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, and diarrhea.
    † Participants had previously received at least one dose of a COVID-19 vaccine prior to the study.
    ‡ CDC-defined high-risk condition for severe COVID-19: https://www.cdc.gov/covid/hcp/clinical-care/underlying-conditions.html
    a A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Original and Omicron variant lineages BA.4/BA.5
    b Moderna COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)
    c Person-months is defined as the total months from study injection date to the date of event (COVID-19), date of off-study COVID-19 vaccine, last date of study participation, death date or efficacy data cutoff date, whichever is the earliest.
    d Descriptive relative Vaccine Efficacy (rVE) = 1-hazard ratio (MNEXSPIKE vs comparator vaccine). Hazard ratio and CI are estimated using a stratified Cox proportional hazard model (stratified by age group per randomization) with Efron's method of tie handling and with the treatment group as a fixed effect.
    e Descriptive relative vaccine efficacy means that these endpoints were not hypothesis-tested and do not necessarily make valid inferences about vaccine efficacy.

    MNEXSPIKEa

    Comparator Vaccineb

    Descriptive rVEd

    (95% CI)e

     

    Participants

    (N)

     

    COVID-19

    Cases

    (n)

     

    Incidence Rate of COVID-19 Per 100 Person-Monthsc

     

    Participants

    (N)

     

    COVID-19

    Cases

    (n)

     

    Incidence Rate of COVID-19 Per 100 Person-Monthsc

     

    2,469

    243

    1.3

    2,466

    287

    1.6

    15.7%

    (0, 29.0%)e

    The primary immunogenicity analysis population included 621 participants who received MNEXSPIKE and 568 participants who received the comparator vaccine. Among participants assessed for immunogenicity, 45.3% were male, 54.7% were female, 13.5% were Hispanic or Latino, 80.7% were White, 11.9% were Black or African American, 4.0% were Asian, <0.1% were American Indian or Alaska Native, <0.1% were Native Hawaiian or Pacific Islander, 0.3% were other races, and 2.1% were Multiracial.

    The primary immunogenicity analyses evaluated the ratio of neutralizing antibody geometric mean concentrations (GMC) and the difference in seroresponse rate (SRR) against a pseudovirus expressing Omicron BA.4/BA.5 and the original SARS-CoV-2 Spike protein (D614G) following vaccination with MNEXSPIKE compared with vaccination with the comparator vaccine.

    MNEXSPIKE met the pre-specified noninferiority criterion of the lower bound of the 95% CI of GMC ratio >0.667, and the pre-specified noninferiority criterion of the lower bound of the 95% CI of the SRR-difference >-10%. These analyses are summarized in Table 13 and Table 15. Descriptive analyses of GMC and SRR by age subgroup are summarized in Table 14 and Table 16.

    Table 13: Comparison of Geometric Mean Concentration 28 Days After a Single Dose of MNEXSPIKE vs 28 Days After a Single Dose of Comparator Vaccine – Per-Protocol Immunogenicity Subset*

    N=Number of participants with non-missing data at the corresponding timepoint(s).
    * Per-Protocol Immunogenicity Subset included a randomly selected subset of subjects (Immunogenicity Subset) who received study vaccine, did not have a major protocol deviation that impacted immune response, and had both pre-dose and post-dose immunogenicity assessment at timepoint of primary interest (28 days post-dose). Participants had previously received at least one dose of a COVID-19 vaccine prior to the study.
    a Geometric mean concentration (GMC) was determined using a SARS-CoV-2 Spike-Pseudotyped Virus Neutralization Assay. Quantification of SARS-CoV-2 neutralizing antibodies utilizes SARS-CoV-2 Reporter Virus Particles which express GFP for quantitative measurement of infection by counting the number of green fluorescent cells (assay readout [count] is Foci Forming Units [FFUs]). The serum antibody concentration (Ab[C]) of the neutralizing antibodies was determined by interpolating the mean of the replicate FFU values off the fitted reference standard curve (AU/mL).
    b A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Original and Omicron variant lineages BA.4/BA.5
    c The log-transformed antibody levels are analyzed using an analysis of covariance (ANCOVA) model with the group variable (MNEXSPIKE vs comparator vaccine) as fixed effect, adjusted by SARS-CoV-2 infection status at baseline, randomization age group, number of prior COVID-19 boosters (0, 1, 2, ≥3), and type of last prior COVID-19 vaccine. Coefficients for Least Square Means use margins by level. The resulted LS means, difference of LS means, and 95% CI are back transformed to the original scale for presentation.
    d Moderna COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)
    Note: Antibody values < the lower limit of quantitation (LLOQ) are replaced by 0.5 × LLOQ. Values > the upper limit of quantitation (ULOQ) are replaced by the ULOQ if actual values are not available.

    Assaya

     

    MNEXSPIKEb

    GMC

    N=621

    (95% CI)c

     

    Comparator Vaccined

    GMC

    N=568

    (95% CI)c

     

    GMC Ratio

    (MNEXSPIKE/ Comparator Vaccine)

    (95% CI)c

     

    Omicron BA.4/BA.5

    2340.9

    (2167.0, 2528.8)

    1753.8

    (1618.2, 1900.7)

    1.3

    (1.2, 1.5)

    Original SARS-CoV-2 (D614G)

    10631.9

    (9960.2, 11348.9)

    8576.5

    (8012.5, 9180.1)

    1.2

    (1.1, 1.4)
    Table 14: Descriptive Analysis of Geometric Mean Concentration by Age Subgroup 28 Days After a Single Dose of MNEXSPIKE vs 28 Days After a Single Dose of Comparator Vaccine – Per-Protocol Immunogenicity Subset*

    N=Number of participants in the corresponding age group.
    * Per-Protocol Immunogenicity Subset included a randomly selected subset of subjects (Immunogenicity Subset) who received study vaccine, did not have a major protocol deviation that impacted immune response, and had both pre-dose and post-dose immunogenicity assessment at timepoint of primary interest (28 days post-dose). Participants had previously received at least one dose of a COVID-19 vaccine prior to the study.
    a Geometric mean concentration (GMC) was determined using a SARS-CoV-2 Spike-Pseudotyped Virus Neutralization Assay. Quantification of SARS-CoV-2 neutralizing antibodies utilizes SARS-CoV-2 Reporter Virus Particles which express GFP for quantitative measurement of infection by counting the number of green fluorescent cells (assay readout [count] is Foci Forming Units [FFUs]). The serum antibody concentration (Ab[C]) of the neutralizing antibodies was determined by interpolating the mean of the replicate FFU values off the fitted reference standard curve (AU/mL).
    b A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Original and Omicron variant lineages BA.4/BA.5
    c The log-transformed antibody levels are analyzed using an analysis of covariance (ANCOVA) model with the group variable (MNEXSPIKE vs comparator vaccine) as fixed effect, adjusted by SARS-CoV-2 infection status at baseline, number of prior COVID-19 boosters (0, 1, 2, ≥3), and type of last prior COVID-19 vaccine. Coefficients for Least Square Means use margins by level. The resulted LS means, difference of LS means, and 95% CI are back transformed to the original scale for presentation.
    d Moderna COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)
    Note: Antibody values < the lower limit of quantitation (LLOQ) are replaced by 0.5 × LLOQ. Values > the upper limit of quantitation (ULOQ) are replaced by the ULOQ if actual values are not available.

    Assaya

     

    Age Subgroup (Years)

     

    MNEXSPIKEb

    GMC

    (95% CI)c

     

    Comparator Vaccined

    GMC

    (95% CI)c

     

    GMC Ratio

    (MNEXSPIKE/ Comparator Vaccine)

    (95% CI)c

     

    Omicron BA.4/BA.5

    12 to <18

    N=91

    3561.4

    (3037.5, 4175.7)

    N=93

    3398.9

    (2908.9, 3971.4)

    1.0

    (0.8, 1.3)

    18 to <65

    N=378

    2120.6

    (1917.3, 2345.6)

    N=316

    1661.0

    (1487.8, 1854.4)

    1.3

    (1.1, 1.5)

    ≥65

    N=152

    2339.5

    (1984.3, 2758.3)

    N=159

    1326.8

    (1130.0, 1557.7)

    1.8

    (1.4, 2.2)

    Original SARS-CoV-2 (D614G)

    12 to <18

    N=91

    13617.7

    (12006.3, 15445.3)

    N=93

    12404.3

    (10966.5, 14030.6)

    1.1

    (0.9, 1.3)

    18 to <65

    N=378

    9734.8

    (8938.8, 10601.7)

    N=316

    8251.3

    (7517.2, 9057.1)

    1.2

    (1.0, 1.3)

    ≥65

    N=152

    11451.1

    (9936.3, 13196.9)

    N=159

    7463.3

    (6499.4, 8570.1)

    1.5

    (1.3, 1.9)
    Table 15: Comparison of Seroresponse Rate 28 Days After a Single Dose of MNEXSPIKE vs 28 Days After a Single Dose of Comparator Vaccine – Per-Protocol Immunogenicity Subset*

    N=Number of participants with non-missing data at the corresponding timepoint(s).
    * Per-Protocol Immunogenicity Subset included a randomly selected subset of subjects (Immunogenicity Subset) who received study vaccine, did not have a major protocol deviation that impacted immune response, and had both pre-dose and post-dose immunogenicity assessment at timepoint of primary interest (28 days post-dose). Participants had previously received at least one dose of a COVID-19 vaccine prior to the study.
    a A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Original and Omicron variant lineages BA.4/BA.5
    b Seroresponse is defined as an antibody value change from baseline below the LLOQ to ≥4 × LLOQ, or at least a 4-fold rise if baseline is ≥ LLOQ and <4 × LLOQ, or at least a 2-fold rise if baseline is ≥4 × LLOQ, where baseline refers to pre-dose.
    c 95% CI is calculated using the Clopper-Pearson method.
    d Moderna COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)
    e 95% CI is calculated using the Miettinen-Nurminen (score) confidence limits.

    Assay

     

    MNEXSPIKEa

    Seroresponse Rateb

    N=621

    %

    (95% CI)c

     

    Comparator Vaccined

    Seroresponse Rateb

    N=568

    %

    (95% CI)c

     

    Difference in

    Seroresponse Rate

    (MNEXSPIKE-Comparator Vaccine)

    %

    (95% CI)e

     

    Omicron BA.4/BA.5

    79.9

    (76.5, 83.0)

    65.5

    (61.4, 69.4)

    14.4

    (9.3, 19.4)

    Original SARS-CoV-2 (D614G)

    83.6

    (80.4, 86.4)

    72.9

    (69.0, 76.5)

    10.7

    (6.0, 15.4)
    Table 16: Descriptive Analysis of Seroresponse Rate by Age Subgroup 28 Days After a Single Dose of MNEXSPIKE vs 28 Days After a Single Dose of Comparator Vaccine – Per-Protocol Immunogenicity Subset*

    N=Number of participants in the corresponding age group.
    * Per-Protocol Immunogenicity Subset included a randomly selected subset of subjects (Immunogenicity Subset) who received study vaccine, did not have a major protocol deviation that impacted immune response, and had both pre-dose and post-dose immunogenicity assessment at timepoint of primary interest (28 days post-dose). Participants had previously received at least one dose of a COVID-19 vaccine prior to the study.
    a A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Original and Omicron variant lineages BA.4/BA.5
    b Seroresponse is defined as an antibody value change from baseline below the LLOQ to ≥4 × LLOQ, or at least a 4-fold rise if baseline is ≥ LLOQ and <4 × LLOQ, or at least a 2-fold rise if baseline is ≥4 × LLOQ, where baseline refers to pre-dose.
    c 95% CI is calculated using the Clopper-Pearson method.
    d Moderna COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)
    e 95% CI is calculated using the Miettinen-Nurminen (score) confidence limits.

    Assay

     

    Age Subgroup

    (Years)

     

    MNEXSPIKEa

    Seroresponse Rateb

    %

    (95% CI)c

     

    Comparator Vaccined

    Seroresponse Rateb

    %

    (95% CI)c

     

    Difference in

    Seroresponse Rate

    (MNEXSPIKE-Comparator Vaccine)

    %

    (95% CI)e

     

    Omicron BA.4/BA.5

    12 to <18

    N=91

    87.9

    (79.4, 93.8)

    N=93

    80.6

    (71.1, 88.1)

    7.3

    (-3.4, 18.0)

    18 to <65

    N=378

    79.6

    (75.2, 83.6)

    N=316

    63.6

    (58.0, 68.9)

    16.0

    (9.3, 22.7)

    ≥65

    N=152

    75.7

    (68.0, 82.2)

    N=159

    60.4

    (52.3, 68.0)

    15.3

    (4.9, 25.3)

    Original SARS-CoV-2 (D614G)

    12 to <18

    N=91

    85.7

    (76.8, 92.2)

    N=93

    74.2

    (64.1, 82.7)

    11.5

    (-0.1, 23.1)

    18 to <65

    N=378

    83.1

    (78.9, 86.7)

    N=316

    75.9

    (70.8, 80.6)

    7.1

    (1.1, 13.2)

    ≥65

    N=152

    83.6

    (76.7, 89.1)

    N=159

    66.0

    (58.1, 73.4)

    17.5

    (8.0, 26.9)

    Immunogenicity of Single Dose (Monovalent Omicron XBB.1.5) in Vaccine-Experienced

    Study 2 is a Phase 3 randomized, observer-blind, active-controlled clinical trial that evaluated the immunogenicity and safety of MNEXSPIKE in participants 12 years of age and older in Japan. Randomization was stratified by age: 12 years through 17 years, 18 years through 64 years, and 65 years of age and older. 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 2 months before enrollment, as well as participants with stable human immunodeficiency virus (HIV) infection. A total of 692 participants were randomized in a 1:1 ratio to receive MNEXSPIKE (n=344), a vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Omicron XBB.1.5 lineage, or comparator vaccine (SPIKEVAX 2023-2024 Formula [n=348]). All participants had previously received at least one dose of a COVID-19 vaccine prior to the study with a median interval of 16.7 months since the last dose.

    The primary immunogenicity analysis population included 334 participants who received MNEXSPIKE and 334 participants who received the comparator vaccine. Among participants assessed for immunogenicity, 65.0% were male, 35.0% were female, and all participants were Asian. The median age of participants was 52 years (range 12 through 83 years) and 20.7% of participants were 65 years of age and older.

    The primary immunogenicity analyses evaluated the ratio of neutralizing antibody geometric mean concentrations (GMC) against a pseudovirus expressing Omicron XBB.1.5 SARS-CoV-2 Spike protein following vaccination with MNEXSPIKE compared to vaccination with the comparator vaccine. MNEXSPIKE met the pre-specified noninferiority criterion of the lower bound of the 95% CI of the GMC ratio >0.667 (Table 17). A descriptive analysis of the difference in seroresponse rates is summarized in Table 18.

    Table 17: Comparison of Geometric Mean Concentration 28 Days After a Single Dose of MNEXSPIKE vs 28 Days After a Single Dose of Comparator Vaccine – Per-Protocol Immunogenicity Set*

    N=Number of participants with non-missing data at baseline and the corresponding timepoint(s).
    * Per-Protocol Immunogenicity Set included subjects who received study vaccine, did not have a major protocol deviation that impacted immune response, and had both pre-dose and post-dose immunogenicity assessment at timepoint of primary interest (28 days post-dose). Participants had previously received at least one dose of a COVID-19 vaccine prior to the study.
    a Geometric mean concentration (GMC) was determined using a SARS-CoV-2 Spike-Pseudotyped Virus Neutralization Assay. Quantification of SARS-CoV-2 neutralizing antibodies utilizes SARS-CoV-2 Reporter Virus Particles which express GFP for quantitative measurement of infection by counting the number of green fluorescent cells (assay readout [count] is Foci Forming Units [FFUs]). The serum antibody concentration (Ab[C]) of the neutralizing antibodies was determined by interpolating the mean of the replicate FFU values off the fitted reference standard curve (AU/mL).
    b A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Omicron XBB.1.5
    c The log-transformed antibody levels are analyzed using an analysis of covariance (ANCOVA) model with the group variable (MNEXSPIKE vs comparator vaccine) as fixed effect, adjusted by SARS-CoV-2 infection status at baseline, randomization age group, number of prior COVID-19 boosters (0, 1, 2, ≥3), and type of last prior COVID-19 vaccine. LS means are based on the observed margins. The resulted LS means, difference of LS means, and 95% CI are back transformed to the original scale for presentation.
    d SPIKEVAX 2023-2024 Formula
    Note: Antibody values < the lower limit of quantitation (LLOQ) are replaced by 0.5 × LLOQ. Values > the upper limit of quantitation (ULOQ) are replaced by the ULOQ if actual values are not available.

    Assaya

     

    MNEXSPIKEb

    GMC

    (95% CI)c

    N=334

     

    Comparator Vaccined

    GMC

    (95% CI)c

    N=334

     

    GMC Ratio

    (MNEXSPIKE/ Comparator Vaccine)

    (95% CI)c

     

    Omicron XBB.1.5

    1757.2

    (1580.1, 1954.3)

    1470.4

    (1322.4, 1635.0)

    1.2

    (1.0, 1.4)
    Table 18: Comparison of Seroresponse Rate 28 Days After a Single Dose of MNEXSPIKE vs 28 Days After a Single Dose of Comparator Vaccine – Per-Protocol Immunogenicity Set*

    N=Number of participants with non-missing data at baseline and the corresponding timepoint(s).
    * Per-Protocol Immunogenicity Set included subjects who received study vaccine, did not have a major protocol deviation that impacted immune response, and had both pre-dose and post-dose immunogenicity assessment at timepoint of primary interest (28 days post-dose). Participants had previously received at least one dose of a COVID-19 vaccine prior to the study.
    a A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Omicron XBB.1.5
    b Seroresponse is defined as an antibody value change from baseline below the LLOQ to ≥4 × LLOQ, or at least a 4-fold rise if baseline is ≥ LLOQ and <4 × LLOQ, or at least a 2-fold rise if baseline is ≥4 × LLOQ, where baseline refers to pre-dose.
    c 95% CI is calculated using the Clopper-Pearson method.
    d SPIKEVAX 2023-2024 Formula
    e 95% CI is calculated using the Miettinen-Nurminen (score) confidence limits.

    Assay

     

    MNEXSPIKEa

    Seroresponse Rateb

    %

    (95% CI)c

    N=334

     

    Comparator Vaccined

    Seroresponse Rateb

    %

    (95% CI)c

    N=334

     

    Difference in

    Seroresponse Rate

    (MNEXSPIKE-Comparator Vaccine)

    %

    (95% CI)e

     

    Omicron XBB.1.5

    92.2

    (88.8, 94.9)

    86.8

    (82.7, 90.3)

    5.4

    (0.8, 10.2)

    Immunogenicity of Single Dose (Monovalent Omicron XBB.1.5) in Vaccine-Naïve

    In a separate observer-blind, active-controlled portion of Study 1, the immunogenicity of MNEXSPIKE was evaluated in participants 12 years of age and older in the United States. 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 2 months before enrollment, as well as participants with stable human immunodeficiency virus (HIV) infection. A total of 1,056 participants (COVID-19 vaccine-naïve [n=400] and COVID-19 vaccine-experienced [n=656]) received MNEXSPIKE, a vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Omicron variant lineage XBB.1.5.

    The immunogenicity analysis population included 371 vaccine-naïve participants and 617 vaccine-experienced participants who received MNEXSPIKE. Among vaccine-naïve participants assessed for immunogenicity, 48.2% were male, 51.8% were female, 36.4% were Hispanic or Latino, 55.3% were White, 43.1% were Black or African American, 0.5% were American Indian or Alaska Native, and 0.3% were Multiracial. The median age of participants was 38 years (range 12 through 81 years) and 8.1% of participants were 65 years of age and older. Among vaccine-experienced participants assessed for immunogenicity, 46.0% were male, 54.0% were female, 14.1% were Hispanic or Latino, 73.3% were White, 17.2% were Black or African American, 2.9% were Asian, 0.5% were American Indian or Alaska Native, 0.2% were Native Hawaiian or Pacific Islander, 0.2% were other races, and 5.7% were Multiracial. The median age of participants was 16 years (range 12 years through 83 years) and 8.6% of participants were 65 years of age and older.

    Descriptive immunogenicity analyses evaluated the ratio of neutralizing antibody geometric mean concentrations (GMC) and the difference in seroresponse rate (SRR) against a pseudovirus expressing Omicron XBB.1.5 SARS-CoV-2 Spike protein following vaccination with MNEXSPIKE in vaccine-naïve participants compared with vaccine-experienced participants (Table 19 and Table 20).

    Table 19: Descriptive Analysis of Geometric Mean Concentration 28 Days After a Single Dose of MNEXSPIKE in COVID-19 Vaccine-Naïve vs COVID-19 Vaccine-Experienced Participants – Per-Protocol Immunogenicity Subset*

    N=Number of participants with non-missing data at the corresponding timepoint(s).
    * Per-Protocol Immunogenicity Subset included a randomly selected subset of subjects (Immunogenicity Subset) who received study vaccine, and did not have a major protocol deviation that impacted immune response and had both pre-dose and post-dose immunogenicity assessment at timepoint of primary interest (28 days post-dose).
    a A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Omicron variant lineage XBB.1.5
    b Geometric mean concentration (GMC) was determined using a SARS-CoV-2 Spike-Pseudotyped Virus Neutralization Assay. Quantification of SARS-CoV-2 neutralizing antibodies utilizes SARS-CoV-2 Reporter Virus Particles which express GFP for quantitative measurement of infection by counting the number of green fluorescent cells (assay readout [count] is Foci Forming Units [FFUs]). The serum antibody concentration (Ab[C]) of the neutralizing antibodies was determined by interpolating the mean of the replicate FFU values off the fitted reference standard curve (AU/mL).
    c The log-transformed antibody levels are analyzed using an analysis of covariance (ANCOVA) model with the group variable (vaccine-naïve vs vaccine-experienced) as fixed effect, adjusted by randomization age group. Least Square Means use observed margins. The resulted LS means, difference of LS means, and 95% CI are back transformed to the original scale for presentation.
    Note: Antibody values < the lower limit of quantitation (LLOQ) are replaced by 0.5 × LLOQ. Values > the upper limit of quantitation (ULOQ) are replaced by the ULOQ if actual values are not available.

    Assayb

     

    MNEXSPIKEa

    Vaccine-Naïve

    GMC

    N=371

    (95% CI)c
     

    Vaccine-Experienced

    GMC

    N=617

    (95% CI)c

     

    GMC Ratio

    (Vaccine-Naïve/ Vaccine-Experienced)

    (95% CI)c

     

    Omicron XBB.1.5

    2934.9

    (2559.3, 3365.6)

    2640.3

    (2386.8, 2920.8)

    1.1

    (0.9, 1.3)
    Table 20: Descriptive Analysis of Seroresponse Rate 28 Days After a Single Dose of MNEXSPIKE in COVID-19 Vaccine-Naïve vs COVID-19 Vaccine-Experienced Participants – Per-Protocol Immunogenicity Subset*

    N=Number of participants with non-missing data at the corresponding timepoint(s).
    * Per-Protocol Immunogenicity Subset included a randomly selected subset of subjects (Immunogenicity Subset) who received study vaccine, and did not have a major protocol deviation that impacted immune response and had both pre-dose and post-dose immunogenicity assessment at timepoint of primary interest (28 days post-dose).
    a A vaccine encoding the membrane-bound, linked NTD and RBD of the S glycoprotein from SARS-CoV-2 Omicron variant lineage XBB.1.5
    b Seroresponse is defined as an antibody value change from baseline below the LLOQ to ≥4 × LLOQ, or at least a 4-fold rise if baseline is ≥ LLOQ and <4 × LLOQ, or at least a 2-fold rise if baseline is ≥4 × LLOQ, where baseline refers to pre-dose.
    c 95% CI is calculated using the Clopper-Pearson method.
    d 95% CI is calculated using the Miettinen-Nurminen (score) confidence limits.

    Assay

     

    MNEXSPIKEa

    Vaccine-Naïve

    Seroresponse Rateb

    N=371

    %

    (95% CI)c

     

    Vaccine-Experienced

    Seroresponse Rateb

    N=617

    %

    (95% CI)c

     

    Difference in

    Seroresponse Rate

    (Vaccine-Naïve-Vaccine-Experienced)

    %

    (95% CI)d

     

    Omicron XBB.1.5

    91.1

    (87.7, 93.8)

    86.5

    (83.6, 89.1)

    4.6

    (0.4, 8.4)
  • 15 REFERENCES

    • 1. Jain SS, Anderson SA, Steele JM, et al. Cardiac manifestations and outcomes of COVID-19 vaccine-associated myocarditis in the young in the USA: longitudinal results from the Myocarditis After COVID Vaccination (MACiV) multicenter study. Lancet. 2024;76:1-13. https://doi.org/10.1016/j.eclinm.2024.102809
  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    MNEXSPIKE (2025-2026 Formula) is supplied as follows:

           NDC: 80777-400-62                 Carton of 1 single-dose prefilled syringe containing 1 dose of 0.2 mL (NDC: 80777-400-17)

           NDC: 80777-400-61                 Carton of 2 single-dose prefilled syringes, each syringe containing 1 dose of 0.2 mL (NDC: 80777-400-17)

           NDC: 80777-400-60                 Carton of 10 single-dose prefilled syringes, each syringe containing 1 dose of 0.2 mL (NDC: 80777-400-17)

    Storage

    Store frozen between -40°C to -15°C (-40°F to 5°F).

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

    After thawing, MNEXSPIKE may be stored refrigerated between 2°C to 8°C (36°F to 46°F) for up to 90 days or up to the expiration date printed on the carton, whichever comes first.

    After thawing, MNEXSPIKE may be stored between 8°C to 25°C (46°F to 77°F) for up to 24 hours.

    Do not refreeze once thawed.

    Thawed syringes can be handled in room light conditions.

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

    Thawed prefilled 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°F to 46°F), prefilled syringes should not be refrozen and should be stored at 2°C to 8°C (36°F to 46°F) until use.

  • 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 MNEXSPIKE.

    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.

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

    ©2025 ModernaTX, Inc. All rights reserved.
    MNEXSPIKE is a trademark of ModernaTX, Inc.
    Patent(s): www.modernatx.com/patents

    US Govt. License No. 2256

    Revised: 8/2025

  • Information for Recipients and Caregivers

    MNEXSPIKE (pronounced em nex' spyk)
    (COVID-19 Vaccine, mRNA)
    (2025-2026 Formula)

    Please read this information sheet before getting MNEXSPIKE. 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 MNEXSPIKE?

    MNEXSPIKE is a vaccine to protect against COVID-19. MNEXSPIKE is for people who are:

    • 65 years of age and older, or
    • 12 years through 64 years of age at high risk for severe COVID-19.

    Vaccination with MNEXSPIKE may not protect all people who receive the vaccine.

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

    Who should not get MNEXSPIKE?

    You should not get MNEXSPIKE if you had:

    • a severe allergic reaction after a previous dose of either MNEXSPIKE, SPIKEVAX (COVID-19 Vaccine, mRNA), or any Moderna COVID-19 vaccine.
    • a severe allergic reaction to any ingredient of this vaccine (see What are the ingredients in MNEXSPIKE?)

    What should I tell my healthcare provider?

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

    • have any allergies
    • had a severe allergic reaction after receiving a previous dose of any COVID-19 vaccine
    • have had myocarditis (inflammation of the heart muscle) or pericarditis (inflammation of the lining outside the heart)
    • have a fever
    • have a bleeding disorder or are on a blood thinner
    • are immunocompromised or are on a medicine that affects your immune system
    • are pregnant or plan to become pregnant
    • are breastfeeding
    • have received any other COVID-19 vaccine
    • have ever fainted in association with an injection

    How is MNEXSPIKE given?

    MNEXSPIKE is given as an injection into the muscle.

    What are the risks of MNEXSPIKE?

    There is a very small chance that MNEXSPIKE 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 MNEXSPIKE. 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:

    • Trouble breathing
    • Swelling of your face and throat
    • A fast heartbeat
    • A rash all over your body
    • Dizziness and weakness

    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. Myocarditis and pericarditis following administration of mRNA COVID-19 vaccines have occurred most commonly in males 12 years through 24 years of age. In most of these people, symptoms began within a week following vaccination. Based on available data, estimated rates of myocarditis and/or pericarditis from 1 through 7 days after getting a dose of the 2023-2024 Formula of mRNA COVID-19 vaccines were approximately 8 cases per million doses in people 6 months through 64 years of age and approximately 27 cases per million doses in males 12 years through 24 years of age.

    In most people who have had myocarditis or pericarditis after receiving an mRNA COVID-19 vaccine, symptoms have gone away a few days after receiving treatment with medicines used to reduce inflammation.

    In a study, follow-up information was collected on people who developed myocarditis after receiving the original formula of a COVID-19 vaccine; most people had received an mRNA COVID-19 vaccine. Some people in the study reported having heart symptoms approximately 3 months after developing myocarditis. Some people in the study had heart MRIs (scans that show detailed images of the heart muscle) initially after developing myocarditis and again approximately 5 months later. The initial and follow-up heart MRIs commonly showed signs of injury to the heart muscle, with improvement over time in most people. It is not known if these heart MRI findings might predict long-term heart effects of myocarditis. Studies are underway to find out if there are long-term heart effects in people who have had myocarditis after receiving an mRNA COVID-19 vaccine.

    You should seek medical attention right away if you or your child has any of the following symptoms after receiving MNEXSPIKE, particularly during the 2 weeks after receiving the vaccine:

    • Chest pain
    • Shortness of breath
    • Feelings of having a fast-beating, fluttering, or pounding heart

    These could be symptoms of myocarditis or pericarditis.

    Side effects that have been reported in clinical trials with MNEXSPIKE include:

    • Injection site reactions: pain, tenderness and swelling of the lymph nodes in the same arm of the injection, swelling (hardness), and redness.
    • General side effects: fatigue, headache, muscle pain, joint pain, chills, nausea, vomiting, and fever.

    These may not be all of the possible side effects of MNEXSPIKE. 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.

    What are the ingredients in MNEXSPIKE?

    MNEXSPIKE contains the following ingredients:

    • messenger ribonucleic acid (mRNA)
    • lipids (SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC])
    • tromethamine
    • tromethamine hydrochloride
    • sucrose

    MNEXSPIKE does not contain preservatives.

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

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

    ©2025 Moderna. All rights reserved.
    MNEXSPIKE is a trademark of ModernaTX, Inc.
    Patent(s): www.modernatx.com/patents
    Revised: August 2025

  • PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

    mNEXSPIKE (COVID-19 Vaccine, mRNA) 2025-2026 Formula Injectable Suspension for Intramuscular Use Single-Dose Pre-Filled Syringe 0.2 mL

    COVID-19 Vaccine, mRNA

    mNEXSPIKE

    2025-2026 Formula

    NDC: 80777-400-17

    0.2 mL Single Dose

    Rx Only

    For IM Use

    Mfd. for: Moderna, US Inc.

  • PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

    mNEXSPIKE (COVID-19 Vaccine, mRNA) 2025-2026 Formula Injectable Suspension for Intramuscular Use Single-Dose Pre-Filled Syringe Carton 0.2 mL (<a href=/NDC/80777-400-60>80777-400-60</a>)

    NDC: 80777-400-60

    Moderna

    Rx Only

    COVID-19 Vaccine, mRNA

    mNEXSPIKE

    2025-2026 Formula

    Injectable Suspension, for Intramuscular Use

    For 65 years and older

    For 12 years through 64 years at high risk for severe COVID-19

    10 Single-Dose Pre-Filled Syringes

    Each dose is 0.2 mL

  • PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

    mNEXSPIKE (COVID-19 Vaccine, mRNA) 2025-2026 Formula Injectable Suspension for Intramuscular Use Single-Dose Pre-Filled Syringe Carton 0.2 mL (<a href=/NDC/80777-400-61>80777-400-61</a>)

    NDC: 80777-400-61

    Rx Only

    COVID-19 Vaccine, mRNA

    mNEXSPIKE

    2025-2026 Formula

    Injectable Suspension, for Intramuscular Use

    For 65 years and older

    For 12 years through 64 years at high risk for severe COVID-19

    2 Single-Dose Pre-Filled Syringes

    Each dose is 0.2 mL

  • PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

    mNEXSPIKE (COVID-19 Vaccine, mRNA) 2025-2026 Formula Injectable Suspension for Intramuscular Use Single-Dose Pre-Filled Syringe Carton 0.2 mL (<a href=/NDC/80777-400-62>80777-400-62</a>)

    NDC: 80777-400-62

    Rx Only

    COVID-19 Vaccine, mRNA

    mNEXSPIKE

    2025-2026 Formula

    Injectable Suspension, for Intramuscular Use

    For 65 years and older

    For 12 years through 64 years at high risk for severe COVID-19

    1 Single-Dose Pre-Filled Syringe

    Each dose is 0.2 mL

  • INGREDIENTS AND APPEARANCE
    MNEXSPIKE 
    covid-19 vaccine, mrna injection, suspension
    Product Information
    Product TypeVACCINEItem Code (Source)NDC: 80777-400
    Route of AdministrationINTRAMUSCULAR
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    CX-052075 (UNII: KFZ2Z65LB6) (CX-052075 - UNII:KFZ2Z65LB6) CX-05207510 ug  in 0.2 mL
    Inactive Ingredients
    Ingredient NameStrength
    SM-102 (UNII: T7OBQ65G2I)  
    1,2-DIMYRISTOYL-RAC-GLYCERO-3-METHOXYPOLYETHYLENE GLYCOL 2000 (UNII: 9X2596CIE0)  
    CHOLESTEROL (UNII: 97C5T2UQ7J)  
    1,2-DISTEAROYL-SN-GLYCERO-3-PHOSPHOCHOLINE (UNII: 043IPI2M0K)  
    TROMETHAMINE (UNII: 023C2WHX2V)  
    TROMETHAMINE HYDROCHLORIDE (UNII: 383V75M34E)  
    SUCROSE (UNII: C151H8M554)  
    WATER (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 80777-400-6010 in 1 CARTON
    1NDC: 80777-400-170.2 mL in 1 SYRINGE, PLASTIC; Type 3: Prefilled Biologic Delivery Device/System (syringe, patch, etc.)
    2NDC: 80777-400-612 in 1 CARTON
    2NDC: 80777-400-170.2 mL in 1 SYRINGE, PLASTIC; Type 3: Prefilled Biologic Delivery Device/System (syringe, patch, etc.)
    3NDC: 80777-400-621 in 1 CARTON
    3NDC: 80777-400-170.2 mL in 1 SYRINGE, PLASTIC; Type 3: Prefilled Biologic Delivery Device/System (syringe, patch, etc.)
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    BLABLA12583508/27/2025
    Labeler - Moderna US, Inc. (117626450)
    Establishment
    NameAddressID/FEIBusiness Operations
    ModernaTX, Inc.116912313ANALYSIS(80777-400) , API MANUFACTURE(80777-400)
    Establishment
    NameAddressID/FEIBusiness Operations
    Rovi Pharma Industrial Services S.A.463584525ANALYSIS(80777-400)
    Establishment
    NameAddressID/FEIBusiness Operations
    Rovi Pharma Industrial Services S.A.469527153MANUFACTURE(80777-400) , ANALYSIS(80777-400)
    Establishment
    NameAddressID/FEIBusiness Operations
    Rovi Pharma Industrial Services S.A.462117953ANALYSIS(80777-400) , LABEL(80777-400) , PACK(80777-400)
    Establishment
    NameAddressID/FEIBusiness Operations
    MODERNA BIOTECH SPAIN SL.469713566ANALYSIS(80777-400)
    Establishment
    NameAddressID/FEIBusiness Operations
    Associates of Cape Cod076574078ANALYSIS(80777-400)
    Establishment
    NameAddressID/FEIBusiness Operations
    Eurofins Advantar Laboratories, LLC849636258ANALYSIS(80777-400)

    • Trademark Results [mNEXSPIKE]

    Mark Image

    Registration | Serial
    Company
    Trademark
    Application Date
    MNEXSPIKE
    MNEXSPIKE
    98341867 not registered Live/Pending
    ModernaTX, Inc.
    2024-01-04
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