Foundayo: which tox species, and why?

“Toxicology studies of orforglipron were conducted in Wistar rats and cynomolgus monkeys.”

“Wistar rats were selected as the most suitable rodent species; however, rats represent an off-target model of toxicology. Cynomolgus monkeys were selected as the nonrodent species because they are a pharmacologically relevant species.”

“Toxicology studies of orforglipron were conducted in Wistar rats and cynomolgus monkeys.”

“Toxicology studies of orforglipron were conducted in Wistar rats and cynomolgus monkeys.”

“Off-target safety was further characterized in several nonpharmacologically relevant species, including rats (general toxicology and reproductive safety assessment), rasH2 transgenic mice (carcinogenicity assessment), and rabbits (reproductive safety assessment).”

“FDA concurs with the Applicant that orforglipron was not carcinogenic in a lifetime study in rats and a 6-month study in rasH2 transgenic mice.”

“The pharmacological characteristics of orforglipron were assessed in vitro (receptor-binding, potency, and specificity) and in vivo (wild-type monkeys and “humanized GLP-1 receptor” Glp1rS33W rats).”