Zavzpret: which tox species, and why?

“Intranasal toxicity studies of zavegepant were conducted in Sprague Dawley rat (4-, 13-, and 26-week) and cynomolgus monkey (4-, 13-, and 39-week).”

“similar binding affinity was observed to the CGRP receptors in cynomolgus (IC50 = 0.06 nM) and marmoset (IC50 = 0.13 nM) monkeys. In vitro binding affinity was substantially lower to the CGRP receptors in the other animal species tested (IC50 values of 500, 600, 8,700, 25,000, and 140,000 nM for beagle dog, guinea pig, rabbit, rat, and mouse, respectively).”

“Monkey: zavegepant was administered at doses of 0, 7.5, 17, and 25 mg/day in the 4-week intranasal study, at doses of 0, 18, 27, and 36 mg/day in the 13-week study, and at doses of 0, 18, 36, and 45 mg/day in the 39-week study.”

“Intranasal toxicity studies of zavegepant were conducted in Sprague Dawley rat (4-, 13-, and 26-week) and cynomolgus monkey (4-, 13-, and 39-week).”

“A standard battery of reproductive and developmental toxicology studies was conducted for zavegepant in Sprague Dawley rat and New Zealand White rabbit. The studies were conducted using subcutaneous administration to increase systemic exposure.”

“A 26-week study in Tg.rasH2 mouse and a 2-year study in SD rat were conducted to assess the carcinogenic potential of BHV-3500. Both studies were negative for carcinogenicity.”

“Therefore, monkey was the only pharmacologically relevant species for on-target toxicities.”