mRESVIA 50 micrograms dispersion for injection – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

mRESVIA 50 micrograms dispersion for injection

respiratory syncytial virus (RSV) mRNA Vaccine (nucleoside modified)

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

This is a single-dose vial that contains one dose of 0.5 mL.

One dose (0.5 mL) contains 50 micrograms of RSV mRNA (nucleoside modified) encapsulated in lipid nanoparticles.

The active substance is a single-stranded 5’ capped mRNA encoding the RSV-A glycoprotein F stabilised in the prefusion conformation.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Dispersion for injection

White to off-white dispersion (pH: 7.1 – 7.8).

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

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

mRESVIA should be used in accordance with official recommendations.

4.2 Posology and method of administration

Posology

The recommended dose is one single dose of 0.5 mL (50 micrograms).

Method of administration

For intramuscular injection only, preferably in the deltoid muscle of the upper arm.

The vaccine must not be injected intravenously, subcutaneously or intradermally and must not be mixed with other vaccines.

For instructions for preparation of the medicinal product before administration and special handling requirements, see section 6.6.

For precautions to be taken before administering the vaccine, see section 4.4.

Paediatric population

The safety and efficacy of mRESVIA in children have not been established.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Hypersensitivity and anaphylaxis

Appropriate medical treatment and supervision should always be readily available in case of a severe hypersensitivity reaction, including anaphylaxis, following administration of the vaccine.

Anxiety-related reactions

Anxiety-related reactions including vasovagal reactions (syncope), hyperventilation or stress-related reactions may occur in association with vaccination as a psychogenic response to the needle injection. It is important that precautions are in place to avoid injury from fainting.

Concurrent illness

Vaccination should be postponed in individuals suffering from acute infection or febrile illness. The presence of a minor infection, such as a cold, should not delay vaccination.

Thrombocytopenia and coagulation disorders

As with other intramuscular injections, the vaccine should be given with caution in individuals receiving anticoagulant therapy or those with thrombocytopenia or any coagulation disorder (such as haemophilia) because bleeding or bruising may occur following an intramuscular administration in these individuals.

Immunocompromised individuals

Safety and immunogenicity data on mRESVIA are not available for immunocompromised individuals. Patients receiving immunosuppressant therapy or with immunodeficiency may have a diminished immune response to mRESVIA.

Duration of protection

The duration of protection afforded by mRESVIA is unknown (see section 5.1).

Limitations of vaccine effectiveness

As with all vaccines, vaccination with mRESVIA may not protect all vaccine recipients.

Excipients with known effect

Sodium

This vaccine contains less than 1 mmol sodium (23 mg) per 0.5 mL dose, that is to say essentially ‘sodium-free.’

4.5 Interaction with other medicinal products and other forms of interaction

No formal interaction studies with other medicinal products have been performed.

No data on concomitant administration of mRESVIA with other vaccines are currently available.

4.6 Fertility, pregnancy and lactation

Women of childbearing potential

mRESVIA is not indicated in women of childbearing potential. It is not to be used in women who are or may be pregnant or breast-feeding (see section 4.1).

Pregnancy

There are no or limited amount of data from the use of mRESVIA in pregnant women. Animal studies with mRESVIA do not indicate direct or indirect harmful effects with respect to pregnancy (see section 5.3).

Breast-feeding

It is unknown whether mRESVIA is excreted in human milk.

Fertility

No human data on the effect of mRESVIA on fertility are available.

Animal studies with mRESVIA do not indicate direct or indirect harmful effects with respect to female reproductive toxicity. Animal studies are insufficient to assess male reproductive toxicity (see section 5.3).

4.7 Effects on ability to drive and use machines

mRESVIA has no or negligible influence on the ability to drive and use machines. However, some of the effects mentioned under section 4.8 (fatigue), may temporarily affect the ability to drive or use machines.

4.8 Undesirable effects

Summary of the safety profile

The most commonly reported adverse reactions were injection site pain (56%), fatigue (31%), headache (27%), myalgia (26%) and arthralgia (22%). Most solicited local and systemic adverse reactions occurred within 1 to 2 days after injection and resolved within 1 to 2 days after onset. The majority of these reactions were mild in intensity.

Tabulated list of adverse reactions

The safety profile presented below is based on data generated in a global placebo-controlled Phase 2/3 clinical study conducted in 22 countries in Central and Latin America, Africa, Asia Pacific, North America and Europe. A total of 18 245 adult participants aged ≥60 years received one injection of 50 microgram mRESVIA. The main characteristics of the patient population are described in section 5.1.

Adverse reactions reported are listed according to the following frequency convention:

Very common (≥1/10)

Common (≥1/100 to <1/10)

Uncommon (≥1/1 000 to <1/100)

Rare (≥1/10 000 to <1/1 000)

Very rare (<1/10 000)

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness (Table 1).

Table 1. Adverse reactions following administration of mRESVIA

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

No case of overdose has been reported in the clinical studies.

In case of overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment instituted immediately.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Vaccine, other viral vaccine, ATC code: J07BX05

Mechanism of action

mRESVIA is a lipid nanoparticle-encapsulated mRNA-based vaccine encoding the membrane-anchored RSV-A F glycoprotein and stabilised in the prefusion conformation through structural engineering. The F protein exists in two primary conformational states, prefusion and post-fusion. The prefusion state facilitates entry into the host cell through a conformational change to the post-fusion state. The prefusion F glycoprotein is the target of neutralising antibodies that mediate protection against RSV-associated respiratory tract disease. The RSV-A prefusion glycoprotein is antigenically cross-reactive to the RSV-B prefusion glycoprotein.

mRESVIA stimulates secretion of antibodies that neutralise RSV-A and RSV-B subtypes and induction of antigen-specific cellular immune responses.

Clinical efficacy and safety

The safety and efficacy of mRESVIA to prevent RSV-LRTD in adults ≥60 years of age, with or without underlying medical conditions, was evaluated in a randomised, placebo-controlled, observer-blind, case-driven clinical study. This study was conducted in 22 countries from North America/Europe, Central/Latin America, Africa, and Asian/Pacific regions with a follow-up of 24 months after vaccination.

Participants were randomised to a single dose of mRESVIA (50 micrograms) or placebo (in a 1:1 ratio). Randomisation was stratified by age (60 to 74 years; ≥75 years) and risk factors for LRTD, i.e. congestive heart failure (CHF) and/or chronic obstructive pulmonary disease (COPD). 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.

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. The study participants included 51% male with 63% White, 12% Black or African American and 9% Asian. The median age was 67 years (range 60-96 years), with 31% of participants between 70 and 79 years and 6% of participants ≥80 years. A total of 7.0% had protocol-defined LRTD risk factors (CHF and/or COPD) and 29% had one or more comorbidity of interest (COPD, asthma, chronic respiratory disease, diabetes, CHF, advanced liver disease, or advanced renal disease).

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 as RT-PCR-confirmed RSV infection with 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% of participants had reached 6 months of follow-up. 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 after a median of 18.8 months of follow-up (see Table 2).

Table 2. Efficacy of mRESVIA to prevent first episode of protocol-defined RSV-LRTD (per-protocol efficacy set)

Abbreviations: RSV-LRTD = Respiratory Syncytial Virus-Lower Respiratory Tract Disease; N = number of participants in Per-Protocol Efficacy set; n = number of participants with protocol defined RSV-LRTD; CI = Confidence Interval. * Vaccine efficacy (VE) is defined as 100% x (1 - hazard ratio (mRESVIA vs. placebo)). The CI for VE is based on a stratified Cox proportional hazard model with Efron's method of tie handling and with the treatment group as a fixed effect, adjusting for stratification factors at randomisation.

† For primary analysis for RSV-LRTD with 2 or more symptoms, 95.04% CI where the alpha value of 4.96% was derived from the Lan-DeMets approximation to the Pocock stopping boundary with an information fraction of 0.99 (85 out of total of 86 cases). For primary analysis for RSV-LRTD with 3 or more symptoms, 95.10% CI where the alpha value of 4.90% was derived from the Lan-DeMets approximation to the Pocock stopping boundary with an information fraction of 0.97 (31 out of total of 32 cases). Pre-specified success criterion of lower bound alpha-adjusted CI above 20%.

‡ For additional analyses for RSV-LRTD with 2 or more and 3 or more symptoms, 95% CI.

In a post-hoc analysis, VE for the period 12 months to 24 months post injection was 30.0% (95% CI: 1.1%, 50.7%) and 36.0% (95% CI: -12.6, 64.3%) against RSV-associated LRTD with ≥2 symptoms and ≥3 symptoms, respectively.

Descriptive vaccine efficacy analysis by age subgroup and for participants with at least one comorbidity is presented in Table 3.

Table 3. Efficacy of mRESVIA to prevent first episode of RSV-LRTD with 2 or more signs/symptoms by subgroup (per-protocol efficacy set)

Abbreviations: RSV-LRTD = Respiratory Syncytial Virus-associated Lower Respiratory Tract Disease

* Vaccine efficacy (VE) is defined as 100% x (1 - hazard ratio (mRESVIA vs.

placebo)). The CI for VE is based on a stratified Cox proportional hazard model with Efron's method of tie handling and with the treatment group as a fixed effect, adjusting for stratification factors at randomisation. † Based on the number of participants in each subgroup.

‡ VE cannot be reliably estimated due to the low number of cases accrued in this age group.

§ Comorbidities included in this analysis were chronic cardiopulmonary conditions, including CHF, COPD, asthma and chronic respiratory conditions as well as diabetes, advanced liver, and advanced kidney disease.

Paediatric population

The licensing authority has deferred the obligation to submit the results of studies with mRESVIA in one or more subsets of the paediatric population in prevention of respiratory syncytial virus (RSV)-associated lower respiratory tract disease (LRTD), as per paediatric investigation plan (PIP) decision, for the granted indication (see section 4.2 for information on paediatric use).

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

Non-clinical data reveal no special hazards for humans based on conventional studies of repeat toxicity, genotoxicity, and developmental and reproductive toxicity.

General toxicity

General toxicity studies were conducted in rats at doses that exceed the human dose of mRESVIA (intramuscularly with mRESVIA up to two dose administrations once every 3 weeks or intramuscularly receiving up to four dose administrations of other related mRNA (nucleoside modified)-encapsulated lipid nanoparticle vaccine drug products once every 2 weeks. Transient and reversible injection site oedema and erythema and transient and reversible changes in laboratory tests (including increases in eosinophils, activated partial thromboplastin time and fibrinogen) were observed. Results suggest the toxicity potential to humans is low.

Genotoxicity/carcinogenicity

In vitro genotoxicity studies were conducted to evaluate the lipid components SM-102 and PEG2000-DMG in the vaccine. In vivo genotoxicity studies were conducted with related mRNA (nucleoside modified)-encapsulated lipid nanoparticle drug products. Results suggest the genotoxicity potential to humans is very low. Consistent with regulatory guidelines, carcinogenicity studies were not performed because this is a vaccine product.

Developmental and reproductive toxicity

In a combined developmental and reproductive toxicity study, mRESVIA was administered to female rats 4 times intramuscularly at 96 micrograms/dose (twice prior to mating [28 and 14 days prior] and twice after mating [on gestation days 1 and 13]). Anti-RSV antibodies were present in maternal animals from prior to mating to the end of the study on lactation day 21, as well as in foetuses and offspring, and maternal milk. There were no vaccine-related adverse effects on female fertility, pregnancy, embryo foetal or offspring development or postnatal development.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Heptadecan-9-yl 8-((2-hydroxyethyl) (6-oxo-6-(undecyloxy) hexyl) amino)octanoate Cholesterol

1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)

1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG2000-DMG) Trometamol

Trometamol hydrochloride

Acetic acid

Sodium acetate trihydrate

Sucrose

Water for injections

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products or diluted.

6.3 Shelf life

1 year at -40°C to -15°C.

Within the shelf life of 1 year, the vaccine is stable for 30 days when stored at 2°C to 8°C and protected from light. At the end of 30 days, the vaccine should be used immediately or discarded.

Once thawed, the vaccine should not be refrozen.

Upon moving the vaccine to 2°C to 8°C storage, the outer carton should be marked with the new expiry date at 2°C to 8°C.

If the vaccine is received at 2°C to 8°C, it should be stored at 2°C to 8°C. The expiry date on the outer carton should have been marked with the new expiry date at 2°C to 8°C.

The vials may be stored at 8°C to 25°C for a total of 24 hours after removal from refrigerated conditions. Within this period of time, vials may be handled in ambient light conditions. Do not refrigerate after being stored at 8°C to 25°C. Discard the vial if not used within this time.

6.4 Special precautions for storage

Store in a freezer between -40°C to -15°C.

Keep the vials in the original carton in order to protect from light. For storage conditions after thawing of the vaccine, see section 6.3.

6.5 Nature and contents of container

0.5 mL dispersion in a glass vial with a rubber stopper and a purple flip-off plastic cap with aluminium seal.

The single-dose vial is packaged within a carton containing 10 single-dose vials.

Pack sizes:

10 single-dose vials per carton

Each single-dose vial contains 0.5 mL.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

This vaccine should be administered by a trained healthcare professional using aseptic techniques to ensure sterility.

Handling instructions for mRESVIA before use

Store vials in a freezer between -40°C to -15°C.

The vaccine is ready to use once thawed.

Do not shake or dilute the product. Swirl the vial gently after thawing and before withdrawal.

The single-dose vial is for single use only.

Do not use if the vial has been dropped or damaged or the security seal on the carton has been broken.

mRESVIA is shipped and supplied as a frozen single-dose vial (see section 6.4) that must be completely thawed before use. Thaw each vial, either in the refrigerator or at room temperature, following the instructions in Table 4. The remaining vials must continue to be stored in their original carton in the freezer or refrigerator.

Table 4. Thawing conditions and times based on presentation and temperature before use

• After thawing, the vaccine cannot be refrozen.
• If the vaccine has been thawed at room temperature (15°C to 25°C), the vial is ready to administer. Vials should not be returned to the refrigerator after being thawed at room temperature.
• The vial may be stored at 8°C to 25°C for a total of 24 hours after after removal from refrigerated conditions. Within this period of time, vials may be handled in ambient light conditions. Discard the vial if not used within this time.

Administration

• Remove a vial from the carton.

• The vaccine should be inspected visually for particulate matter and

  discolouration prior to administration. mRESVIA is a white to off-white dispersion. It may contain white or translucent product-related particulates. Do not administer if vaccine is discoloured or contains other particulate matter.

• Administer the entire dose intramuscularly.

Disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

MODERNA BIOTECH SPAIN, S.L.

C/ Julián Camarillo nº 31

28037 Madrid

Spain

8 MARKETING AUTHORISATION NUMBER(S)

PL 53720/0018

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

10/06/2026

10 DATE OF REVISION OF THE TEXT

10/06/2026