Regulatory Decision Summary for Supemtek

Three studies were submitted to support the safety, efficacy and immunogenicity of Supemtek (RIV4): two with RIV4 (PSC12 and PSC16) and one with the trivalent recombinant influenza vaccine (RIV3; PSC04). The RIV3 study is relevant to RIV4 because both vaccines are manufactured using the same process and have overlapping compositions.

Study PSC12 was to support the indication in subjects ≥50 years of age. In the study, the vaccine efficacy of RIV4 was demonstrated, as it met the pre-specified primary objective for non-inferiority, relative to IIV4 (Fluarix Tetra) in protecting against rtPCR-confirmed protocol-defined ILI; the rVE over IIV4 against rtPCR-positive Influenza was 30% (95% CI: 10; 47%). RIV4 also met the rVE criterion for non-inferiority for several exploratory analyses.

Studies PSC16 and PSC04 were submitted to support the indication in subjects 18-49 years of age. In Study PSC16, RIV4 demonstrated non-inferior immunogenicity as compared to IIV4 against 3 of the 4 antigens present in the vaccine. Non-inferior immunogenicity against the B/Victoria antigen was not demonstrated, and may be partly due to antigenic differences between the B/Victoria rHA and the egg-grown B/Victoria antigen used in the HI assay. In addition, Study PSC4 provided efficacy data for RIV3, and support the use of RIV4 in adults 18-49 years of age.

In both Study PSC12 and Study PSC16, the local and systemic reactions recorded for both vaccines were not unexpected for influenza vaccines in terms of nature, frequency and severity. The reactogenicity and adverse event (AE) rates were generally comparable between RIV4 and IIV4 groups. The most frequently reported solicited local AEs in RIV4 recipients was tenderness, followed by local pain. The most frequently reported solicited systemic AEs in RIV4 recipients were headache, fatigue, joint and muscle pain. There were no serious adverse events (SAE) considered causally related to RIV4. In addition, safety data from studies with RIV3 and post-market experiences with RIV3 and RIV4 did not identify special safety concerns.

In both Study PSC12 and Study PSC04, the majority of laboratory-confirmed influenza cases were caused by A strains, and there were relatively fewer cases due to B strains. In addition, the immunogenicity against the B/Victoria strain in the RIV4 group was lower compared to the IIL4 group, although it may be partly due to antigenic differences between the B/Victoria rHA present in RIV4 and the egg-based B/Victoria antigen used in the HI assay. However, the same attack rates of influenza B strains were observed in both the RIV4 and IIV4 groups in Study PSC12, suggesting a similar efficacy of the two vaccines.

In the submitted clinical studies, no data were available in special populations (e.g. immunocompromised individuals, and pregnant and breast feeding women). Such limitations are not unique to RIV4, and recommendations on the use of RIV4 in special populations have been clearly labelled in the Product Monograph for Supemtek.

In conclusion, the benefit risk assessment for RIV4 is favorable and supports the use of RIV4 in subjects aged 18 years and older.