Zavzpret: genotox, carcinogenicity and repro: done or skipped?

“Zavegepant was negative for mutagenicity and clastogenicity in an adequate battery of genetic toxicology (Ames, in vitro chromosomal aberration in Chinese hamster ovary cells, and in vivo rat micronucleus) assays.”

“Intranasal administration of zavegepant (0, 0.3, 0.8, or 2.5 mg/day) to Tg.rasH2 mice for 26 weeks resulted in no evidence of drug-related tumors. Intranasal administration of zavegepant (0, 2, 9, or 18.8 mg/kg/day) to rats for up to 96 weeks resulted in no evidence of drug-related tumors.”

“Reproductive and developmental toxicology studies were conducted in SD rat and New Zealand White rabbit. There were no reproductive or developmental toxicities at doses resulting in drug exposures at least 2,000-fold higher than human exposure (i.e., AUC) at the proposed clinical dose.”

“There were no effects of BHV-3500 on cardiovascular or respiratory safety pharmacology endpoints in cynomolgus monkey or Sprague Dawley (SD) rat, respectively. The IC50 for hERG inhibition in transfected HEK293 cells was in excess of 30 µM.”