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

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.

Administer MRESVIA intramuscularly.

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

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

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

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.

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.

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.

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

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)].

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

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

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 80777-345-89      Carton of 2 single-dose pre-filled plastic syringes in a blister pack containing 2 doses of 0.5 mL (NDC 80777-345-01). Use one syringe per person per dose.

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.

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):

• Pre-filled plastic syringes may be stored refrigerated between 2°C to 8°C (36°F to 46°F) for up to 90 days prior to use.

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

• Pre-filled plastic syringes may be stored between 8°C to 25°C (46°F to 77°F) for a total of 24 hours after removal from refrigerated conditions. Discard the pre-filled syringe if not used within this time. Syringes should not be returned to the refrigerator after being thawed at room temperature.
• Total storage at 8°C to 25°C (46°F to 77°F) must not exceed 24 hours.
• Do not refreeze once thawed. Do not shake.

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°F 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.