Mnexspike Injection, Suspension
FDA Label NDC 80777-400

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.

For intramuscular use.

• 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.

Administer MNEXSPIKE intramuscularly.

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.

MNEXSPIKE is an injectable suspension.

A single dose is 0.2 mL.

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.

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

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).

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

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

MNEXSPIKE may not protect all vaccine recipients.

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%).

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.

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.

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.

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.

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.

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.

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.

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)].

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).

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.

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.

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)].

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).

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

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.

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.

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.

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).

• 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

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.

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

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

Mnexspike (covid-19 Vaccine, Mrna) 2025-2026 Formula Injectable Suspension For Intramuscular Use Single-dose Pre-filled Syringe 0.2 mL (Image 01)

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.

Mnexspike (covid-19 Vaccine, Mrna) 2025-2026 Formula Injectable Suspension For Intramuscular Use Single-dose Pre-filled Syringe Carton 0.2 mL (80777-400-60) (Image 02)

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

Mnexspike (covid-19 Vaccine, Mrna) 2025-2026 Formula Injectable Suspension For Intramuscular Use Single-dose Pre-filled Syringe Carton 0.2 mL (80777-400-61) (Image 03)

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

Mnexspike (covid-19 Vaccine, Mrna) 2025-2026 Formula Injectable Suspension For Intramuscular Use Single-dose Pre-filled Syringe Carton 0.2 mL (80777-400-62) (Image 04)

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