Itvisma: what was done before first-in-human, and what came after?

“In vivo toxicology/safety studies conducted in NHPs utilized a single IT administration of OAV101 at 1.2 x 1013 vg/animal, considered equivalent to the proposed starting clinical dose level for ITVISMA of 1.2x1014 vg/patient based on a 10-fold difference in CSF volume between NHP and human.”

“No carcinogenicity, genotoxicity, or repeat dosing were conducted for OAV101B. These studies are not necessary based on the intended ROA, dosing regimen (i.e., single infusion), known product characteristics, and overall safety profile for this class of product.”

“A single IT dose of onasemnogene abeparvovec was administered at three dose levels: 1.20 × 10 13 vg/animal (equivalent to the clinical therapeutic dose), 3.0 × 10 13 vg/animal, and 6.0 × 10 13 vg/animal.”

“Fertility and early embryonic development (FEED) studies were conducted in healthy male and female FVB mice administered a single intravenous injection of OAV101B.”

“Fertility and early embryonic development (FEED) studies were conducted in healthy male and female FVB mice administered a single intravenous injection of OAV101B. There were no reported adverse effects on fertility, fecundity, or mating behaviors in either sex.”

“No carcinogenicity, genotoxicity, or repeat dosing were conducted for OAV101B.”

“No carcinogenicity, genotoxicity, or repeat dosing were conducted for OAV101B. These studies are not necessary based on the intended ROA, dosing regimen (i.e., single infusion), known product characteristics, and overall safety profile for this class of product.”

“No carcinogenicity, genotoxicity, or repeat dosing were conducted for OAV101B. These studies are not necessary based on the intended ROA, dosing regimen (i.e., single infusion), known product characteristics, and overall safety profile for this class of product.”