Opdivo: which tox species, and why?

“The nonclinical toxicity studies of nivolumab were performed in a battery of nonGLP studies, and GLP- and ICH-compliant in vitro tissue binding studies in multiple species and in vivo toxicology studies in cynomolgus monkeys.”

“Nivolumab bound to PD-1 from humans and cynomolgus monkeys to a similar extent and blocked the interaction of PD-1 with its ligands. Nivolumab did not bind to PD-1 from rodents or rabbits.”

“Because nivolumab was unable to bind to PD-1 from rodents, the Applicant developed a murine surrogate anti-PD-1 antibody to investigate the effects of PD-1 pathway inhibition on tumor growth.”

“Pivotal 1- and 3-month IV repeat-dose toxicity studies of nivolumab alone were conducted in cynomolgus monkeys.”

“In an enhanced pre- and post-natal development study in cynomolgus monkeys, nivolumab was administered to pregnant dams twice weekly at dose levels of 10 or 50 mg/kg”

“Carcinogenicity studies were not required to support the licensing application for a product to treat advanced human cancer”

“Since nivolumab does not recognize mouse PD-1, a surrogate anti-mouse PD-1 antibody (4H2) was derived to assess the efficacy of PD-1 blockade on tumor growth in syngenic tumor models.”