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

“The in vitro Ames assay and in vivo mouse micronucleus assays were negative. Although an in vitro chromosomal aberration assay was positive, a clastogenic response was only evident at cytotoxic concentrations (mitotic index ≥50%).”

“Carcinogenicity assessment in two rodent species is considered necessary as a post marketing requirement.”

“Administration of daily oral doses of palovarotene to pregnant rats during the period of organogenesis resulted in multiple fetal external, visceral, and skeletal malformations at ≥0.25 mg/kg/day (below clinical exposures), consistent with the pattern of retinoid-mediated embryopathy.”

“Based on safety pharmacology studies conducted to assess the potential for cardiovascular, neurobehavioral, gastrointestinal and urinary effects, palovarotene did not appear to pose any”