Alyftrek: which tox species, and why?

“The GLP-compliant definitive repeat dose VNZ single agent studies were carried out for durations up to 28-days in mouse, 6 months in rat and 9 months in dog.”

“Metabolism was comparable between animal species and humans.”

“The nonclinical program for NDA 218730 primarily focused on evaluation of the safety of the new molecular entity VNZ. The Applicant established a scientific bridge to leverage the nonclinical toxicity data from the IVA program (NDA 203188, Trade name: KALYDECO [tablet]) to characterize the safety profile of D-IVA.”

“The nonclinical safety of VNZ was evaluated in safety pharmacology studies in the rat and dog, repeat dose toxicology studies in the rat and dog of up to 26 and 39 weeks duration, respectively;”

“a full battery of developmental and reproductive toxicology studies in the rat and rabbit; genetic toxicology studies (Ames, in vitro micronucleus, and in vivo rat micronucleus assays);”

“In the case of VNZ, the studies consisted of a 6-month Tg.rasH2 transgenic mouse carcinogenicity study and a 2-year rat carcinogenicity study. VNZ did not demonstrate a carcinogenic potential at the doses evaluated in the Tg.rasH2 mouse up to 30mg/kg/day.”

“A scientific bridge was established between D-IVA and IVA in a 13-week repeat dose toxicology study in rats.”