Regulatory Decision Summary for mResvia

The purpose of this new drug submission (NDS) was to seek market authorization of mResvia (or RSVPreF3 OA) for active immunization for the prevention of Lower Respiratory Tract Disease (LRTD) caused by respiratory syncytial virus (RSV) subtypes A and B in adults 60 years of age (YOA) and older.

After evaluation of the submitted data package, Health Canada authorized mResvia for active immunization for the prevention of Lower Respiratory Tract Disease caused by RSV in adults 60 YOA and older.

Respiratory Syncytial Virus (RSV), a highly contagious human RNA virus, can cause respiratory tract infections in people of all ages. A recently estimated RSV acute respiratory infection (ARI) incidence rate was 6.7 cases/1,000 person-years in adults ≥65 YOA in industrialized countries. Currently no specific treatments for RSV infections and no licensed vaccines for the prevention of RSV-associated diseases are available in Canada for older individuals.

The data supporting the New Drug Submission (NDS) for mRESVIA come from two clinical studies, a pivotal Phase II/III trial and a supportive Phase I trial. The efficacy data of mRESVIA were collected in 35,088 participants 60 years of age and older (17,572 for the active vaccine and 17,516 for the placebo) with a primary analysis (median follow-up of 3.7 months) and a extended analysis (median follow-up of 8.6 months) for Vaccine Efficacy (VE). The primary objective was to demonstrate the efficacy of a single dose of the vaccine in the prevention of RSV-confirmed LRTD during the first season. At primary analysis, the VE of a single dose of mRESVIA against first occurrence of RT-PCR-confirmed LRTD with 2 or more signs/symptoms was 83.7%, and 82.4% for 3 or more signs/symtpoms. The VE of mRESVIA was demonstrated.

mRESVIA was considered safe in adults ≥60 years of age, based on assessment of post-vaccination reactions in the first 7 days, other unsolicited adverse events (AEs) in the first 28 days, and protocol defined adverse events of special interest (AESI) and serious adverse events (SAEs) including deaths throughout the study up to 24 months post-vaccination. The most common AE following mRESVIA vaccination was injection site pain (55.9%), followed by fatigue (30.8%), headaches (26.7%), myalgias (25.6%) and arthralgia (21.7%) occurring mostly in the first 7 days post-vaccines with other types of AEs similar between mRESVIA-recipients and placebo-recipients with no worrisome patterns. There was a numerically higher incidence of events of urticaria in the vaccine group (15 participants) within the first 28 days post-vaccination compared the placebo group (5 participants) with a duration ranging from 3-188 days but all cases resolving. One participant in the mRESVIA group had an SAE of facial paralysis with onset four days after vaccination assessed as related to mRESVIA and lasting 113 days (3.7 months) requiring treatment. There were few deaths or withdrawals from study, with all considered unrelated to vaccine.

Based on the currently available efficacy, immunogenicity and safety evidence, the benefit/risk profile of mRESVIA administered as a single dose in a population ≥60 YOA is favorable.

The recommended dose is 50 µg mRNA-1345 Lipid Nanoparticle (LNP) as a single 0.5 mL dose administered intramuscularly.

The current uncertainties include the level of protection in people aged 80 years and older, and in those with high-risk backgrounds and immunosuppression. A vaccine-class-wide uncertainty is the inability to reliably quantify disease severity to measure clinically meaningful protection more exactly. At this stage, the duration of protection in the target population beyond one RSV season is unclear, and the timing and evidence for a booster dose is not yet clearly established. The sponsor has ongoing trials which address these issues to some extend, with results expected in 2025.

A Risk Management Plan (RMP) for mResvia was reviewed by Health Canada and considered acceptable.

The chemistry and manufacturing information submitted for mResvia has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

Overall, the benefit-harm-uncertainty profile was favourable for mResvia for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

For further details about mResvia, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.