Regulatory Decision Summary for Arexvy

The purpose of this new drug submission (NDS) was to seek market authorization of Arexvy (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 Arexvy 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 this the NDS come from six clinical studies, including four Phase 3 studies. The efficacy data of Arexvy were collected in 24,960 participants 60 years of age and older (12,466 for the vaccine and 12,494 for the placebo) at Vaccine Efficacy (VE) Analysis 1. 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. The median follow-up time in the participants from Day 15 post-vaccination up to Data Lock Point (DLP) on 11 April 2022 was 6.7 months for both groups. The VE of a single dose of Arexvy against first occurrence of RT-PCR-confirmed LRTD was 82.58%. The VE of Arexvy was demonstrated.

Arexvy induced the humoral immune response (neutralizing antibodies [nAb] against RSV-A and RSV-B and RSVPreF3-specific IgG) one month following vaccination. The immune response later decreased, but remained above the baseline values by Month 14. The RSVPreF3-specific CD4+ T cells also increased at Day 31, then declined up to Month 6 but remained well above the baseline value.

Non-inferiority of immunogenicity for Arexvy and quadrivalent influenza (FLU-QIV) vaccine when co-administered compared to when administered separately was demonstrated in term of RSV-A nAb titers and for the hemagglutinin inhibitor antibody (HI Ab) titers for each of the FLU-QIV vaccine strains.

Arexvy was considered safe in adults ≥ 60 years of age, based on assessment of post-vaccination reactions in the first 4 days, other adverse events (AEs) in the first 30 days, and potential immune-mediated diseases (pIMDs) and serious AEs including deaths in the first 6 months. The most common AE following Arexvy vaccination was injection site pain (60.9%), followed by fatigue (33.6%), myalgias (28.9%) and headaches (27.2%) occurring mostly in the first 4 days post-vaccines with other types of AEs similar between Arexvy-recipients and placebo-recipients with no worrisome patterns. There was one case of Guillain-Barré syndrome considered vaccine-related among all participants receiving Arexvy across all clinical trials, and will be monitored in post-marketing surveillance along with other pIMDs.

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

The recommended dose is 120 µg of RSVPreF3 recombinant antigen adjuvanted with AS01E as a single 0.5 mL dose.

Data on vaccine efficacy are currently limited to approximately 6 months post-vaccination; therefore, there is no information on long-term protection by Arexvy.

Available data are insufficient to establish efficacy in participants ≥80 years of age. Reliable efficacy estimates against severe LRTD and hospitalisation caused by RSV in this age group could not be established.

Data in high-risk immunocompromised populations, pregnant women and children are not currently available.