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

“Erdafitinib was not mutagenic in a bacterial reverse mutation (Ames) assay and was not clastogenic in an in vitro micronucleus or an in vivo rat bone marrow micronucleus assay.”

“Not conducted or required to support this NDA application of erdafitinib for patients with advanced cancer.”

“Doses ≥4 mg/kg/day (at total maternal exposures <0.1% of total human exposures at the maximum recommended human dose based on AUC) produced embryo-fetal death, major blood vessel malformations and other vascular anomalies, limb malformations (ectrodactyly, absent or misshapen long bones), an increased incidence of skeletal anomalies in multiple bones (vertebrae, sternebrae, ribs), and decreased fetal weight.”

“In vitro, results from the hERG (IC50 408 nM [or 182 ng/mL]) and ventricular wedge assays demonstrated that erdafitinib has potential for producing QT prolongation and arrhythmia”

“Erdafitinib was not mutagenic in a bacterial reverse mutation (Ames) assay and was not clastogenic in an in vitro micronucleus or an in vivo rat bone marrow micronucleus assay.”

“In vitro, erdafitinib was negative for an increase in reverse mutations in Ames tests in bacteria and for chromosomal aberrations, polyploidy and endoreduplication in a micronucleus test in TK6 cells, respectively.”

“JNJ-42756493-AAA at doses up to and including a dose of 1000 mg/kg was negative in the bone marrow micronucleus assay.”

“Not conducted or required to support this NDA application of erdafitinib for patients with advanced cancer.”

“Carcinogenicity Not conducted or required to support this NDA application of erdafitinib for patients with advanced cancer.”

“In vitro, results from the hERG (IC50 408 nM [or 182 ng/mL]) and ventricular wedge assays demonstrated that erdafitinib has potential for producing QT prolongation and arrhythmia”