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

“Iptacopan was not genotoxic or mutagenic in a battery of in vitro and in vivo assays.”

“Carcinogenicity studies conducted with oral administration of iptacopan in RasH2 transgenic mice with doses up to 1,000 mg/kg/day for 6 months and in rats with doses up to 750 mg/kg/day for 2 years did not identify any carcinogenic potential.”

“In animal reproduction studies, oral administration of iptacopan to pregnant rats and rabbits during organogenesis at exposures 4- to 6-times the human exposure (based on AUC) at the maximum recommended human dose (MRHD) of 200 mg twice daily did not induce embryo or fetal toxicity (see Data) .”

“Iptacopan-related decrease in blood pressure up to 26 mmHg (23%) and a concurrent increase in heart rate up to 40 beats/min (43%) compared to baseline-adjusted values in the control group.”

“There was no evidence of mutagenicity observed.”

“The frequencies of micronucleated binucleated (MNBN) cells were within the normal ranges and iptacopan did not increase micronuclei in human lymphocyte micronucleus assay.”

“Micronucleus assay • No iptacopan-related effects were observed.”

“Carcinogenicity studies conducted with oral administration of iptacopan in RasH2 transgenic mice with doses up to 1,000 mg/kg/day for 6 months and in rats with doses up to 750 mg/kg/day for 2 years did not identify any carcinogenic potential.”

“Carcinogenicity studies conducted with oral administration of iptacopan in RasH2 transgenic mice with doses up to 1,000 mg/kg/day for 6 months and in rats with doses up to 750 mg/kg/day for 2 years did not identify any carcinogenic potential.”

“Concentration: 30, 100, or 300µM hERG current inhibition (Mean ± SEM%) 30: 4.0 ± 1.3 100: 15.5 ± 0.7 300: 30.7 ± 1.5 Positive Control Cisapride (90nM): 62.4 ± 0.3 IC50 > 300 μM”