Ponvory: which tox species, and why?

“The pivotal nonclinical studies were conducted in CD-1 mouse, Wistar rat, beagle dog, and New Zealand White rabbit.”

“In in vitro PD studies ACT-128800 was found to have a 5-fold reduced potency on rat S1P3 receptor as compared to the human counterpart. Nevertheless, the rat is considered a relevant species for the evaluation of the safety of ACT-128800.”

“In rat, oral administration of ponesimod (0, 3, 10, or 30 mg/kg/day in males and 0, 10, 30, or 100 mg/kg/day in females) did not result in an increase in tumors.”

“After chronic treatment for 26 weeks, NOAELs for systemic toxicity were established at 30 mg/kg/day in rats and at 2 mg/kg/day in dogs. In the 52-week toxicity study in dogs, the applicant derived a NOAEL at 3 mg/kg/day.”

“In the reproductive and development studies with oral ponesimod, fertility was not affected in F or M (NOAEL was 100 mg/kg/day), but teratogenicity and fetal lethality was observed in both rats and rabbits.”

“The carcinogenic potential of ponesimod was tested in 2-year oral carcinogenicity studies in CD-1 mouse and Wistar rat.”

“In rat, oral administration of ponesimod (0, 3, 10, or 30 mg/kg/day in males and 0, 10, 30, or 100 mg/kg/day in females) did not result in an increase in tumors.”