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

“In genotoxicity studies, deuruxolitinib was negative in the Ames test, an in vitro chromosome aberration assay, and an in vivo rat bone marrow micronucleus assay. It was positive in an in vitro micronucleus assay.”

“Deuruxolitinib was not carcinogenic in a 6-month oral transgenic mouse carcinogenicity study or a 2-year oral rat carcinogenicity study.”

“In an embryo-fetal toxicity study in rats, lower fetal weight and increased skeletal malformations were noted at 60 mg/kg/day, with no significant maternal toxicity observed.”

“a single oral dose of 10 mg/kg deuruxolitinib induced mild transient decreases in blood pressure, which correlated with mild transient increases in heart rate and decreases in QT interval.”

“In genotoxicity studies, deuruxolitinib was negative in the Ames test, an in vitro chromosome aberration assay, and an in vivo rat bone marrow micronucleus assay.”

“It was positive in an in vitro micronucleus assay. The positive response could be due to a potential aneugenic effect.”

“In genotoxicity studies, deuruxolitinib was negative in the Ames test, an in vitro chromosome aberration assay, and an in vivo rat bone marrow micronucleus assay.”

“Deuruxolitinib was not carcinogenic when administered orally to Sprague Dawley rats once daily for 2 years or to Tg.rasH2 mice once daily for 6 months.”

“Deuruxolitinib was not carcinogenic in a 6-month oral transgenic mouse carcinogenicity study or a 2-year oral rat carcinogenicity study.”

“Also, the corresponding safety margin for free deuruxolitinib based on the in vitro hERG assay deuruxolitinib IC50 ƌĞƐƵůƚ ŽĨ ϭϱϯ ʅD, is at least 3900 times higher than the systemic exposure of 8-mg BID dose.”