mRESVIA Dispersion for injection Ref.[115162] Active ingredients: Respiratory syncytial virus vaccine

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

Mechanism of action

mRESVIA is an mRNA-based vaccine encoding the membrane-anchored RSV-A F glycoprotein stabilised in the prefusion conformation through changes to the amino acid sequence. The RSV-A prefusion glycoprotein is antigenically cross-reactive to the RSV-B prefusion glycoprotein. The prefusion F glycoprotein is the target of neutralising antibodies that mediate protection against RSV-associated respiratory tract disease.

mRESVIA stimulates production of RSV-A and RSV-B neutralising antibodies and induction of antigen-specific cellular immune responses.

Clinical efficacy and safety

Study EUDRA CT number 2021-005026-20 is an ongoing phase ⅔ randomised, observer-blind, placebo-controlled, case-driven pivotal study that was conducted in 22 countries. This study evaluated the safety and efficacy of a single dose of mRESVIA (50 micrograms) to prevent RSV-LRTD in adults ≥60 years with or without underlying medical conditions for up to a year after single vaccination with mRESVIA. Participants were randomised in a 1:1 ratio to mRESVIA or placebo. Randomisation was stratified by age and comorbidities increasing the risk of severe LRTD (see Table 2 and related footnotes).

The primary efficacy analysis population (referred to as the per-protocol efficacy set), included 35 088 participants who received either mRESVIA (n=17 572) or placebo (n=17 516). Most participants were White (63.5%); 12.2% of participants were Black or African American, 8.7% were Asian, and 15.2% reported ‘Other’. A total of 34.6% of participants were Hispanic or Latino. Treatment groups were balanced according to race and ethnicity. Risk factors were balanced between treatment groups.

There were approximately the same number of male and female participants (male 50.9%; female 49.1%). The median age of participants was 67.0 years (range: 60 to 96 years), with 63.5% of participants between 60-69 years, 30.9% of participants between 70 and 79 years and 5.5% 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 6.9% had protocol-defined LRTD risk factors [congestive heart failure (CHF) and/or chronic obstructive pulmonary disease (COPD)] and 29.3% had one or more comorbidity of interest (see Table 2 and related footnotes). A total of 21.8% of the per-protocol efficacy set scored “vulnerable” or “frail” according to Edmonton Frail Scale.

The primary efficacy endpoints were the prevention of a first episode of RSV-associated lower respiratory tract disease (RSV-LRTD) with ≥2 or ≥3 symptoms between 14 days and 12 months post injection. RSV-LRTD was defined by the following criteria: the participant must have had reverse transcription polymerase chain reaction(RT-PCR)-confirmed RSV infection and radiologic evidence of pneumonia or experienced new or worsening of at least 2 or more (or 3 or more) of the following symptoms, lasting for at least 24 hours: shortness of breath, cough and/or fever (≥37.8°C), wheezing and/or rales and/or rhonchi, sputum production, tachypnoea (≥20 breaths per minute or increase of ≥2 breaths per minute from baseline measurement in those who have baseline tachypnoea), hypoxemia (new onset oxygen saturation ≤93% or increasing use of supplemental oxygen), pleuritic chest pain.

The primary efficacy endpoints have been met (lower bound of the alpha-adjusted confidence interval [CI] of the vaccine efficacy [VE] was >20%), including VE of 83.7% (95.88% CI: 66.0%, 92.2%; p<0.0001) against RSV-LRTD as defined by two or more symptoms. The other primary efficacy endpoint against RSV-LRTD defined by three or more symptoms was also met, with a VE of 82.4% (96.36% CI: 34.8%, 95.3%; p=0.0078). These analyses were performed after a median of 3.7 months of follow-up. An additional analysis of efficacy was performed after a median of 8.6 months of follow-up (range 15 to 530 days). A single dose of mRESVIA met the same criterion as defined in the primary analysis for the prevention of RSV-LRTD (lower bound of the 95% CI of the VE was >20%). Vaccine efficacy in adults ≥60 years against RSV-LRTD with 2 or more signs/symptoms was 63.3% (95% CI: 48.7%, 73.7%; number of participants in mRESVIA group was n=47/N=18 112 and in the placebo group was n=127/N=18 045) and against RSV-LRTD with 3 or more signs/symptoms was 63.0% (95% CI: 37.3%, 78.2%; number of participants in mRESVIA group was n=19/N=18 112 and in the placebo group was n=51/N=18 045).

At the time of the additional analysis (median follow up 8.6 months, range 0.5-17.7 months), point estimates of VE in the subgroup analyses by age, comorbidity and frailty were generally consistent with VE of overall population based on the PPE Set (Table 2).

Table 2. Additional analysis of vaccine efficacy (VE) of mRESVIA to prevent first episode of RSV-LRTD (with 2 or more symptoms) 14 days post-injection up to 12 months post-injection by subgroups (per-protocol efficacy set):

^* Based on the number of participants in each subgroup.
^† NA = not applicable due to low number of total cases accrued in this subgroup.
^‡ 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

As shortness of breath is associated with more severe RSV disease, an exploratory analysis was conducted. A total of 54 cases of RSV-LRTD with shortness of breath occurred: 43 in placebo recipients and 11 in mRESVIA recipients.

Paediatric population

The European Medicines Agency 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).