These highlights do not include all the information needed to use MRESVIA safely and effectively. See full prescribing information for MRESVIA.MRESVIATM (Respiratory Syncytial Virus Vaccine)Injectable suspension, for intramuscular useInitial U.S. Approval: 2024

1 INDICATIONS AND USAGE

MRESVIA is indicated for active immunization for the prevention of lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV) in individuals 60 years of age and older.

2 DOSAGE AND ADMINISTRATION

2.1 Dose and Schedule

Administer a single dose (0.5 mL) of MRESVIA as an intramuscular injection.

2.2 Preparation for Administration

MRESVIA is supplied as a pre-filled syringe that contains a frozen suspension that must be thawed prior to administration.

Thaw each syringe before use, either in the refrigerator or at room temperature, following the instructions in Table 1.

• •After thawing, do not refreeze.
• •Do not shake. Syringes should not be returned to the refrigerator after standing at room temperature.
• •Pre-filled syringes may be stored at 8°C to 25°C (46°F to 77°F) for a total of 24 hours after removal from refrigerated conditions. Discard the thawed pre-filled syringe if not used within this time.
• •Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
• •MRESVIA is a white to off-white suspension that may contain visible white or translucent product-related particulates. Do not administer if the vaccine is discolored or contains other particulate matter.

2.3 Administration

Administer MRESVIA intramuscularly.

3 DOSAGE FORMS AND STRENGTHS

MRESVIA is an injectable suspension. A single dose is 0.5 mL.

4 CONTRAINDICATIONS

Do not administer MRESVIA to individuals with a history of a severe allergic reaction (e.g., anaphylaxis) to any component of MRESVIA [see Description (11)].

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 MRESVIA.

5.2 Syncope

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

5.3 Altered Immunocompetence

Immunocompromised individuals, including those receiving immunosuppressive therapy, may have a diminished immune response to MRESVIA.

6 ADVERSE REACTIONS

In a clinical trial (NCT05127434), the most commonly reported (≥10%) adverse reactions were injection‑site pain (55.9%), fatigue (30.8%), headache (26.7%), myalgia (25.6%), arthralgia (21.7%), axillary (underarm) swelling or tenderness (15.2%), and chills (11.6%).

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 to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.

The safety of MRESVIA was evaluated in Study 1 (NCT05127434), a placebo-controlled, observer blinded clinical study conducted in 22 countries that includes participants from North America/ Europe, Central/Latin America, Africa and Asian/Pacific regions. A total of 18,231 participants received MRESVIA and 18,181 received saline placebo (0.5 mL).

In Study 1, the median age of the participants was 67 years (range 60‑108 years). Overall, 51.0% of the participants were male, 49.0% were female, 33.6% were Hispanic or Latino, 61.8% were White, 12.0% were Black or African American, 11.0% were Asian, 4.9% were American Indian or Alaska Native, 0.1% were Native Hawaiian or Pacific Islander, 5.5% were other races, and 4.1% were Multiracial. Demographic characteristics were comparable between participants who received MRESVIA and those who received placebo.

Solicited Adverse Reactions

Local and systemic adverse reactions (ARs) were solicited in an electronic diary for 7 days following injection (i.e., the day of injection and 6 subsequent days) among participants receiving MRESVIA (n=18,160) and participants receiving placebo (n=18,098). Events that persisted for more than 7 days were followed until resolution, but not to exceed 28 days after the study injection.

The percentage of participants who reported solicited local and systemic adverse reactions are presented in Table 2 and Table 3. Solicited local and systemic adverse reactions had a median duration of 1 to 2 days.

Unsolicited Adverse Events

Incidence of unsolicited adverse events, serious adverse events, and medically attended adverse events within 28 days of vaccination were similar in the groups that received MRESVIA or placebo. Unsolicited adverse events within 28 days considered related to the study vaccination were numerically higher in the recipients of MRESVIA (5.7%) than in the placebo recipients (4.4%), primarily attributed to events that were consistent with solicited adverse reactions.

There was a numerically higher incidence of urticaria in the MRESVIA group than the placebo group within 7 days post injection (8 and 2 participants, respectively) and within 28 days post injection (15 and 5 participants, respectively).

Serious Adverse Events

The median duration of safety follow-up was 311 days (range 1 to 585 days), and 96.6% of participants had at least a 6-month follow-up duration after vaccination. SAEs throughout the study were reported by 7.8% and 7.9% of participants in the MRESVIA group and the placebo group, respectively. One participant in the MRESVIA group had an SAE of facial paralysis with onset four days after vaccination assessed as related to MRESVIA. Within 28 days and 42 days post vaccination, there was no imbalance in reports of facial paralysis (including Bell’s palsy) between treatment groups. There were no other notable patterns or numerical imbalances between treatment groups for specific categories of serious adverse events that would suggest a causal relationship to MRESVIA.

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.

MRESVIA is not approved for use in persons younger than 60 years of age.

There are no human data to establish whether there is a vaccine-associated risk with use of MRESVIA in pregnancy.

A developmental toxicity study was performed in female rats administered a vaccine formulation that included approximately twice the amount of nucleoside-modified messenger ribonucleic acid (mRNA), encoding the same RSV fusion (F) glycoprotein stabilized in the prefusion conformation, as in MRESVIA. The vaccine formulation was administered twice prior to mating and twice during gestation. The study revealed no evidence of harm to the fetus due to the vaccine (see Data).

Data

Animal Data

In a developmental toxicity study, 0.2 mL of a vaccine formulation containing 96 mcg of nucleoside‑modified mRNA per dose (a full human dose of MRESVIA contains 50 mcg of nucleoside‑modified mRNA) 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 effects on postnatal development were observed in the study. The developmental toxicity study revealed no evidence of impaired female fertility.

8.2 Lactation

It is not known whether MRESVIA is excreted in human milk. MRESVIA is not approved for use in persons younger than 60 years of age. No human or animal data are available to assess the effects of MRESVIA 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 MRESVIA and any potential adverse effects on the breastfed child from MRESVIA or from the underlying maternal condition. For preventive vaccines, the underlying condition is susceptibility to disease prevented by the vaccine.

8.4 Pediatric Use

Safety and effectiveness of MRESVIA in individuals younger than 18 years of age have not been established.

8.5 Geriatric Use

MRESVIA is approved for use in individuals 60 years of age and older. Of the total number of participants (N = 36,412) who received MRESVIA or placebo in Study 1 (NCT05127434), 22,554 (61.9%) were 60 to 69 years of age, 10,972 (30.1%) were 70 to 79 years of age, and 2,886 (7.9%) were 80 years of age and older [see Adverse Reactions (6.1) and Clinical Studies (14)].

11 DESCRIPTION

MRESVIA is a sterile white to off‑white injectable suspension for intramuscular use.

Each 0.5 mL dose of MRESVIA contains 50 mcg of nucleoside modified mRNA encoding the RSV F glycoprotein stabilized in the prefusion conformation (pre-F protein).

Each 0.5 mL dose of MRESVIA also contains the following ingredients: a total lipid content of 1.02 mg (SM-102 (heptadecan-9-yl 8-((2-hydroxyethyl) (6-oxo-6-(undecyloxy) hexyl) amino) octanoate), polyethylene glycol 2000 dimyristoyl glycerol [PEG2000-DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC]), 0.25 mg tromethamine, 1.2 mg tromethamine hydrochloride, 0.021 mg acetic acid, 0.10 mg sodium acetate trihydrate, 44 mg sucrose, and water for injection.

MRESVIA does not contain a preservative. The rubber tip cap and plunger used for the pre-filled syringe are not made with natural rubber latex.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

MRESVIA induces an immune response against RSV pre-F protein that protects against LRTD caused by RSV.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

MRESVIA has not been evaluated for carcinogenic or mutagenic potential, or impairment of male fertility in animals.

14 CLINICAL STUDIES

Efficacy in Participants 60 Years of Age and Older

Study 1 (NCT05127434) is a randomized, placebo‑controlled, observer‑blind, case‑driven clinical study to evaluate the safety and efficacy of MRESVIA to prevent RSV‑LRTD in individuals 60 years of age and older with or without underlying medical conditions after receipt of a single dose of MRESVIA. Study 1 is being conducted in 22 countries and includes participants from North America/ Europe, Central/Latin America, Africa, and Asian/Pacific regions and is designed to follow participants for up to 24 months after vaccination.

Participants were randomized to a single dose of MRESVIA or placebo (in a 1:1 ratio). Randomization was stratified by age (60 to 74 years; ≥75 years) and risk factors for LRTD, which were defined as congestive heart failure (CHF) and/or chronic obstructive pulmonary disease (COPD) at screening.

The primary efficacy analysis population (Per‑Protocol Efficacy Set) included 35,064 participants who received either MRESVIA (n=17,561) or placebo (n=17,503), with a data cutoff of 30 Nov 2022. This study population included 49.1% female, 50.9% male, 63.4% White, 12.2% Black or African American, 8.7% Asian, 5.1% American Indian or Alaska Native, and 10.6% other. Among participants, 34.7% identified as Hispanic or Latino. The median age of participants was 67 years (range 60‑96 years), with 30.9% of participants between 70 and 79 years and 5.6% of participants ≥80 years. There were no notable differences in demographics or pre‑existing medical conditions between participants who received MRESVIA and those who received placebo. A total of 7.0% had protocol-defined LRTD risk factors (CHF and/or COPD) and 29.5% had one or more comorbidity of interest (COPD, asthma, chronic respiratory disease, diabetes, CHF, advanced liver disease, or advanced renal disease).

Study exclusion criteria included history of myocarditis, pericarditis, or myopericarditis within 2 months prior to screening; autoimmune conditions requiring systemic immunosuppressants (stable HIV‑positive participants were permitted); history of serious reaction to any prior vaccination. Individuals were not eligible for inclusion in the Per-Protocol Efficacy Set if they received any other vaccine within 28 days before or after administration of the study injection.

The primary efficacy endpoints were the prevention of a first episode of RSV‑LRTD with either ≥2 signs/symptoms or ≥3 signs/symptoms starting 14 days after vaccination. RSV-LRTD was defined based on the following criteria: The participant must have had RT-PCR-confirmed RSV infection and experienced new or worsening of ≥2 (or ≥3) of the following signs/symptoms for at least 24 hours: shortness of breath, cough and/or fever (≥37.8°C [100.0°F]), wheezing and/or rales and/or rhonchi, sputum production, tachypnea (≥20 breaths per minute or increase of ≥2 breaths per minute from baseline measurement in those who have baseline tachypnea), hypoxemia (new oxygen saturation ≤93% or new or increasing use of supplemental oxygen), or pleuritic chest pain. If signs/symptoms could not be captured, radiologic evidence of pneumonia with RT-PCR-confirmed RSV infection was also counted as RSV-LRTD.

The primary efficacy analyses were performed when at least 50% of targeted RSV-LRTD cases had accrued [which occurred after a median of 3.7 months of follow-up (range 15 to 379 days) when 20.2% of participants had reached 6 months of follow-up]. Both primary efficacy analyses met the predefined success criterion (lower bound of the alpha-adjusted CI of the VE was >20%). Additional analyses of efficacy were performed after a median of 8.6 months of follow-up (range 15 to 530 days) when 94.2% of participants had reached 6 months of follow-up after vaccination and met the same success criterion (lower bound of the 95% CI of the VE was >20%). Analyses of efficacy for both timepoints are presented in Table 4.

Descriptive vaccine efficacy analyses by age subgroup and for participants with at least one comorbidity are presented in Table 5.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

MRESVIA is supplied as follows:

NDC 80777-345-90     Carton of 1 single-dose pre-filled plastic syringe in a blister pack containing 1 dose of 0.5 mL (NDC 80777-345-01).

NDC 80777-345-96     Carton of 10 single-dose pre-filled plastic syringes, each syringe containing 1 dose of 0.5 mL (NDC 80777-345-01). Each carton contains 5 blisters, and each blister contains two syringes. Use one syringe per person per dose.

16.2 Storage and Handling

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

Frozen Storage

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

Storage after Thawing

Storage at 2°C to 8°C (36°F to 46°F):

Storage at 8°C to 25°C (46°F to 77°F):

Transportation of Thawed Pre-filled Plastic Syringes

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

• •Pre-filled plastic syringes may be stored refrigerated between 2°C to 8°C (36°F to 46°F) for up to 30 days prior to use.

17 PATIENT COUNSELING INFORMATION

Advise the vaccine recipient or caregiver to read the FDA-approved patient labeling (INFORMATION FOR RECIPIENTS AND CAREGIVERS).

Prior to administration of MRESVIA:

This product’s labeling may have been updated. For the most recent prescribing information, please visit modernatx.com/products/mresvia or mRESVIApro.com.

Manufactured for:Moderna US, Inc.5 Vaughn DrivePrinceton, NJ 08540

©2024 ModernaTX, Inc. All rights reserved.

MRESVIA is a trademark of ModernaTX, Inc.

Patent(s): www.modernatx.com/patents

Revised: 05 2024

• •Inform vaccine recipient or caregiver of the potential benefits and risks of vaccination with MRESVIA.
• •Instruct 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 www.vaers.hhs.gov.

INFORMATION FOR RECIPIENTS AND CAREGIVERS

MRESVIA (pronounced em res’ vee ah)

(Respiratory Syncytial Virus Vaccine)

Please read this information sheet before getting MRESVIA. 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 MRESVIA?

MRESVIA is a vaccine to protect you against lower respiratory tract disease caused by Respiratory Syncytial Virus (RSV).

MRESVIA is for people 60 years of age and older. Vaccination with MRESVIA may not protect all people who receive the vaccine.

MRESVIA does not contain RSV. MRESVIA cannot give you lower respiratory tract disease caused by RSV.

Who should not get MRESVIA?

You should not get MRESVIA if you had

What should I tell my healthcare provider?

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

How is MRESVIA given?

MRESVIA is given as an injection into the muscle.

What are the risks of MRESVIA?

There is a very small chance that MRESVIA could cause a severe allergic reaction. A severe allergic reaction would usually occur within a few minutes to one hour after getting a dose of MRESVIA. 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 may include:

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

These may not be all of the possible side effects of MRESVIA. 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 are the ingredients in MRESVIA?

MRESVIA contains the following ingredients:

MRESVIA does not contain preservative.

What if I have additional questions?

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

Manufactured for:Moderna US, Inc.5 Vaughn DrivePrinceton, NJ 08540

©2024 ModernaTX, Inc. All rights reserved.

MRESVIA is a trademark of ModernaTX, Inc.

Patent(s): www.modernatx.com/patents

Revised: 05/2024

• •a severe allergic reaction to any ingredient in MRESVIA (see What are the ingredients in MRESVIA?)

Package/Label Display Panel

Respiratory Syncytial Virus Vaccine  NDC 80777-345-01 For 60 years and older 0.5 mL Single Dose Rx Only For IM Use Mfd. for: Moderna US, Inc.

Package/Label Display Panel

NDC 80777-345-90 Respiratory Syncytial Virus Vaccine mRESVIATM Injectable Suspension For 60 years and older For intramuscular use

Package/Label Display Panel

NDC 80777-345-96 Respiratory Syncytial Virus Vaccine mRESVIATM Injectable Suspension For 60 years and older For intramuscular use