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

“Ponesimod was negative in in vitro (Ames, chromosomal aberration in mammalian cells) and in vivo (micronucleus in rat) assays.”

“In the 2-year rat carcinogenicity study, there were no drug-related increases in neoplasms in M or F. The mouse study was positive for hemangiomas and hemangiosarcomas, with an increase in incidences at all doses in M and in HDF.”

“In the reproductive and development studies with oral ponesimod, fertility was not affected in F or M (NOAEL was 100 mg/kg/day), but teratogenicity and fetal lethality was observed in both rats and rabbits.”

“In cardiovascular safety pharmacology studies, a single oral dose of ponesimod decreased heart rate, blood pressure, and caused first-, second-, and third-degree AV block in guinea pigs.”