Praluent: which tox species, and why?

“The Applicant identified the rat and monkey as pharmacologically relevant species for toxicology testing with alirocumab; both species express PCSK9, to which alirocumab binds with high affinity.”

“Alirocumab was shown to bind human and Cynomolgus monkey PCSK 9 with comparable affinity and lower affinity, but in nanomolar range to mouse, hamster, and rat PCSK9.”

“Repeat dose toxicity studies were conducted in rats and Cynomolgus monkeys.”

“The primary nonclinical toxicity studies of alirocumab were conducted in rats and monkeys for up to 6 months duration with weekly subcutaneous and intravenous dosing.”

“Reproductive toxicity assessments were conducted in rats during the period of embryofetal development at up to 24-fold and in monkeys in an enhanced pre/postnatal development toxicity study at up to 81-fold the 150 mg Q2W human dose, based on plasma exposure.”

“Weight of evidence supported the waiver of carcinogenicity studies with alirocumab; no formal carcinogenicity assessment was conducted, per ICH-S6.”

“The Applicant identified the rat and monkey as pharmacologically relevant species for toxicology testing with alirocumab; both species express PCSK9, to which alirocumab binds with high affinity.”