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

“Umbralisib was not mutagenic in a bacterial mutagenicity (Ames) assay. Umbralisib was not clastogenic in an in vitro micronucleus assay using human (TK6) lymphoblast cells or in an in vivo micronucleus assay in mice at doses up to 1000 mg/kg.”

“No carcinogenicity studies have been conducted or are warranted to support the marketing of umbralisib for the current indications.”

“Malformations were observed at doses of 200 mg/kg/day (cleft palate) and 400 mg/kg/day (cleft palate and nasopharyngeal fistula).”

“An in vitro hERG channel inhibition study (Study # CYP0358-R10) with hERG-expressing cells incubated with umbralisib at concentrations up 100 M showed that the test article had an IC50 greater than the highest dose tested.”

“Umbralisib was not mutagenic in a bacterial mutagenicity (Ames) assay.”

“Umbralisib was not clastogenic in an in vitro micronucleus assay using human (TK6) lymphoblast cells or in an in vivo micronucleus assay in mice at doses up to 1000 mg/kg.”

“Umbralisib was not clastogenic in an in vitro micronucleus assay using human (TK6) lymphoblast cells or in an in vivo micronucleus assay in mice at doses up to 1000 mg/kg.”

“In accordance with the International Council for Harmonisation (ICH) guideline ICH S9 (2009), no carcinogenicity studies have been conducted because umbralisib is intended for use in patients with advanced cancer.”

“No carcinogenicity studies have been conducted or are warranted to support the marketing of umbralisib for the current indications.”

“showed that the test article had an IC50 greater than the highest dose tested. In vivo cardiovascular assessments were conducted as part of a 13-week repeat dose general toxicology study in dogs. ECG examinations showed that umbralisib at doses 30, 100, or 250 mg/kg did not result in any umbralisib-related effects on CV system parameters.”