Retevmo: which tox species, and why?

“To assess the safety of selpercatinib, Loxo conducted GLP-compliant toxicology studies of up to 13-weeks in Sprague Dawley rats and Gottingen mini pigs.”

“Rats (Sprague-Dawley) and minipig (Göttingen) were chosen as relevant rodent and non-rodent species for toxicology program based on pharmacokinetic and metabolic considerations.”

“In a 13-week study in minipigs, male and female animals received selpercatinib at doses of 2, 5, or 15 mg/kg/day for 13 weeks via oral gavage.”

“To assess the safety of selpercatinib, Loxo conducted GLP-compliant toxicology studies of up to 13-weeks in Sprague Dawley rats and Gottingen mini pigs.”

“Because of high fetal toxicity at doses resulting exposures similar to the human exposure at the 160 mg twice daily clinical dose, studies in a second species were not warranted.”

“Selpercatinib was not carcinogenic in a 2-year study in rats when administered by daily oral gavage at doses up to 20 mg/kg in males or 40 mg/kg in females (approximately equal to the human exposure by AUC at the 160 mg twice daily clinical dose). Selpercatinib was not carcinogenic in a 6-month study in rasH2 transgenic mice”

“In a 13-week study in minipigs, male and female animals received selpercatinib at doses of 2, 5, or 15 mg/kg/day for 13 weeks via oral gavage.”