Arexvy: which tox species, and why?

“The Applicant has provided two DART studies with RSVPreF3 (without adjuvant): one in rabbit (doses of 120 μg antigen) and one in rat (doses of 48 μg antigen). In addition, the report from a DART study with the complete product (i.e., RSVPreF3/AS01E; full human dose, 120 μg PreF3) in rabbit was provided.”

“Levels of anti-RSVPreF3 IgG antibodies were increased (measured at Day 32 and 57) in 80% of females and all males administered RSVPreF3 and in 80-90% of females and all males administered RSVPreF3 adjuvanted with AS01B in the first study.”

“The antigen dose is the same as (study COV 8363131) or twice (COV 8384096) the intended clinical dose, however, the clinical formulation is adjuvanted with AS01E instead of AS01B (120 μg RSVPreF3 with 0.5 mL AS01E). 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.”

“Two GLP-compliant repeated dose toxicity studies (and) were conducted in New Zealand White rabbits (10/sex/group), which received three intramuscular injections (Day 1, Day 15 and Day 29, followed by a 4- week recovery period.)”

“The Applicant has provided two DART studies with RSVPreF3 (without adjuvant): one in rabbit (doses of 120 μg antigen) and one in rat (doses of 48 μg antigen). In addition, the report from a DART study with the complete product (i.e., RSVPreF3/AS01E; full human dose, 120 μg PreF3) in rabbit was provided.”

“The absence of carcinogenicity studies is accepted and not required for vaccines.”

“The antigen dose is the same as (study COV 8363131) or twice (COV 8384096) the intended clinical dose, however, the clinical formulation is adjuvanted with AS01E instead of AS01B (120 μg RSVPreF3 with 0.5 mL AS01E). 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.”