Arexvy: what flexibility did regulators accept, and why?

“AS01B contains a double dose of (the same) immuno-enhancers compared to AS01E; therefore, the adjuvant dose can be considered more than the clinical dose. This is acceptable.”

“Therefore, the Applicant stated that the non-clinical PD package was only aiming “to evaluate the need for an adjuvant system in the protein vaccine, and to support the choice of the AS01 adjuvant system in the vaccine formulation with the PreF antigen to elicit potent F-specific CD4+ T cell responses and RSV neutralising antibodies”.”

“This approach can be endorsed. The non-clinical PD studies can thus only be regarded as proof-of-concept immunogenicity studies.”

“Considering the age of the target population, in principle, the absence of reproductive and developmental toxicity studies is acceptable.”

“However, common allometric rules do not apply to a local immune response. Moreover, the analysis of a NOAEL is not an adequate approach, as inflammatory reactions at the site of injection will occur and will be needed for an adequate immune response (i.e., absence of toxicity is not the intention of a vaccine-related toxicity study).”

“Nevertheless, the absolute human dose (or twice the human dose) was used for the repeated dose toxicity studies, which is sufficient.”

“GSK refers to their dossier of Shingrix, for which the adjuvant system was assessed in detail. Considering that AS01 in the currently proposed RSV vaccine is not a new adjuvant, the absence of study reports in this MAA but reference to the Shingrix MAA is acceptable.”