Ensacove: which tox species, and why?

“To assess the safety of ensartinib, the Applicant conducted repeat-dose toxicology studies up to 13 weeks in duration in rats and dogs.”

“Because dog microsomes shared greater metabolic similarities with human microsomes (major metabolites, rate of metabolism, and relative abundance), they were selected by the Applicant as the non-rodent toxicologic species.”

“In the 13-week GLP-compliant toxicology studies, ensartinib was administered QD via oral gavage to rats (12.5, 25, or 50 mg/kg) and dogs (5, 10, or 20/15 mg/kg).”

“In the 13-week GLP-compliant toxicology studies, ensartinib was administered QD via oral gavage to rats (12.5, 25, or 50 mg/kg) and dogs (5, 10, or 20/15 mg/kg).”

“Fertility and early embryonic development studies were not conducted or needed to support the use of ensartinib in the proposed indication per ICH S9. Embryo and Fetal Development Toxicity Study of X-36 Administered Via Oral Gavage in Sprague Dawley Rats”

“Carcinogenicity studies were not conducted or needed to support the use of ensartinib in the currently proposed indication per International Council for Harmonisation (ICH) S9.”

“Ensartinib exhibited in vivo antitumor activity in an immunodeficient murine model of human NSCLC harboring EML4-ALK.”