Zokinvy: which tox species, and why?

“The Sprague Dawley rat and cynomolgus monkey were selected as the main rodent and non-rodent species in the general toxicity studies.”

“The lack of in vitro potency comparison between species was justified by referring to data showing that the amino acid sequence was highly conserved between humans and the relevant nonclinical species rat, mouse, rabbit and monkey.”

“The results of the 1-year oral toxicity study in monkeys indicated that treatment with lonafarnib resulted in histological changes in the male reproductive tract at all doses (10, 20, and 40 mg/kg/day), and in the eye at 40 mg/kg/day.”

“The nonclinical safety profile of lonafarnib was evaluated in cardiovascular safety pharmacology studies in monkeys, repeated dose oral toxicology studies in rats for up to 6 months and in monkeys for up to 1 year”

“Sprague Dawley rat and New Zeeland White rabbits were selected for reproduction and developmental studies.”

“Long-term carcinogenicity studies have not been conducted.”

“Supporting bridging studies in progeria animal models were provided as studies of treatments with other Farnesyl transfer inhibitors (FTIs).”