Sylvant: which tox species, and why?

“General toxicology studies, the embryo-fetal developmental study, and the enhanced pre- and post-natal developmental study (ePPND) were conducted in the cynomolgus monkey, a pharmacologically relevant species.”

“Siltuximab binds to and neutralizes human and non-human primate IL-6 but does not inhibit mouse, rat, dog, pig or guinea pig IL-6. Therefore, the cynomolgus monkey was selected as a pharmacologically relevant species for the toxicology and pharmacokinetics evaluation of siltuximab.”

“A fertility study was conducted with a rat anti-mouse IL6 mAb (CNTO 345) in mice and an enhanced pre- and post-natal development (ePPND) study was conducted with a humanized version of siltuximab (CNTO 136) in cynomolgus monkeys.”

“Toxicology studies were conducted using cynomolgus monkeys because other species available for toxicity testing (rodents and dogs) are not pharmacologically responsive to siltuximab.”

“The potential developmental and reproductive toxicity of siltuximab was investigated in an embryofetal development study in cynomolgus monkeys (T-205-036). Supportive fertility studies in male (Study T-2010-033) and female (Study T-2010-032) mice were conducted using the rat IgG1 isotype anti-mouse IL-6 mAb CNTO 345.”

“Genotoxicity, carcinogenicity and dedicated safety pharmacology studies were not conducted and were not needed for this application.”

“A fertility study was conducted with a rat anti-mouse IL6 mAb (CNTO 345) in mice and an enhanced pre- and post-natal development (ePPND) study was conducted with a humanized version of siltuximab (CNTO 136) in cynomolgus monkeys.”