Portrazza: which tox species, and why?

“Necitumumab bound to EGFR from humans and cynomolgus monkeys with similar affinity, thus, general toxicology studies were conducted in cynomolgus monkeys.”

“As indicated, the binding affinity for EGFR ECD is comparable between human and cyno. Lower affinities were achieved against rodent and rabbit isoforms.”

“The pharmacological and pharmacokinetic data comparing necitumumab and cetuximab are reasonable to support the use of cetuximab as a surrogate for the purpose of investigating the potential for necitumumab to have effects on a developing organism.”

“Necitumumab bound to EGFR from humans and cynomolgus monkeys with similar affinity, thus, general toxicology studies were conducted in cynomolgus monkeys. Monkeys were administered necitumumab weekly for 5 or 26 weeks to investigate the safety of the antibody.”

“Reproductive toxicity studies with necitumumab were not conducted. Instead, the Applicant submitted a literature-based assessment of the antibody’s potential for reproductive toxicity.”

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

“In order look specifically at potential developmental effects following an anti-EGFR antibody, the Applicant provided data by right of reference to a developmental study in non-human primates conducted using cetuximab.”