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

“Ensifentrine was negative for genotoxicity in the following assays: in vitro Ames test for bacterial gene mutation, in vivo comet test (lung and liver) with rats, and in vivo micronucleus assay with mice.”

“A two-year inhalation study in Han Wistar rats and a 6-month oral study in Tg.rasH2 transgenic mice were conducted to assess the carcinogenic potential of ensifentrine. No evidence of tumorigenicity was observed in male and female rats at an exposure approximately 40 times the MRHDID.”

“The male reproductive tract toxicity observed in the rat repeat dose toxicity studies resulted in impaired reproductive performance including decreased mating index and decreased fertility index, increased pre- and post-implantation loss, and decreased live embryos per litter in untreated females at 30 times the MRDHID.”

“A complete battery of safety pharmacology studies has been conducted with ensifentrine. The ensifentrine half maximal inhibitory concentration (IC50) at hERG channels expressed in HEK293 cells was calculated to be 5.62 μM.”