Amvuttra: which tox species, and why?

“The general toxicity of vutrisiran was tested in GLP-compliant subcutaneous (SC) toxicity studies in Sprague Dawley (SD) rat (13-week, 6-month) and cynomolgus monkey (13-week, 9-month).”

“There is complete homology between human and cynomolgus monkey, but not rodent (mouse, rat) or rabbit, TTR mRNA binding regions. Therefore, vutrisiran is pharmacologically active only in monkey.”

“Reductions in serum TTR, Vitamin A, and thyroxine following administration of AD-59206 (a rodent surrogate GalNAc-siRNA; 30 mg/kg/week for 3 doses SC prior to mating, then on GD 6, 12, and 17) were not associated with any adverse effects.”

“The general toxicity of vutrisiran was tested in GLP-compliant subcutaneous (SC) toxicity studies in Sprague Dawley (SD) rat (13-week, 6-month) and cynomolgus monkey (13-week, 9-month).”

“GLP-compliant studies consisted of a fertility and early embryonic development (to implantation) study, an embryofetal development study, and a pre- and postnatal development study in SD rat, and an embryofetal development study in New Zealand White rabbit.”

“Per prior agreement, 2-year carcinogenicity studies of vutrisiran in rat and mouse are to be conducted as post-marketing requirements.”

“Reductions in serum TTR, Vitamin A, and thyroxine following administration of AD-59206 (a rodent surrogate GalNAc-siRNA; 30 mg/kg/week for 3 doses SC prior to mating, then on GD 6, 12, and 17) were not associated with any adverse effects.”