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

“Iberdomide showed increased chromosomal aberrations at ≥ 550 μg/mL in the in vitro clastogenicity assay; however, the results of the Ames assay and in vivo assays were negative for genotoxicity. Given the totality of the data, iberdomide is not considered genotoxic.”

“The FDA confirms that carcinogenicity studies were not conducted and not warranted for the proposed indication.”

“Oral administration of iberdomide in pregnant rats and rabbits during the period of organogenesis resulted in adverse developmental outcomes including embryo-fetal mortality, alterations to growth, and structural abnormalities.”

“The estimated total Cmax at the NOELs or NOAELs in the safety pharmacology studies were approximately 650- and 22-fold higher in rats and monkeys, respectively, than the estimated total Cmax of 6.22 ng/mL at 1 mg QD in RRMM patients. Results from these nonclinical studies indicate a low potential for CV, CNS, or respiratory effects in human subjects at the recommend human dose of 1 mg QD.”

“Iberdomide showed increased chromosomal aberrations at ≥ 550 μg/mL in the in vitro clastogenicity assay; however, the results of the Ames assay and in vivo assays were negative for genotoxicity.”

“Iberdomide showed increased chromosomal aberrations at ≥ 550 μg/mL in the in vitro clastogenicity assay; however, the results of the Ames assay and in vivo assays were negative for genotoxicity. Given the totality of the data, iberdomide is not considered genotoxic.”

“In vivo, iberdomide was not clastogenic in a rat bone marrow micronucleus assay at the maximum tolerated dose of 500 mg/kg/day for 3 days (CC-220-TOX-1344). Under similar experimental conditions, iberdomide did not produce any liver cytotoxicity and did not induce any hepatocyte DNA damage (Comet assay) in rats”

“The FDA confirms that carcinogenicity studies were not conducted and not warranted for the proposed indication.”

“The FDA confirms that carcinogenicity studies were not conducted and not warranted for the proposed indication.”

“The IC50 value for CC-17220 was 91.4 µM, that is >25,000-fold higher than the free fraction Cmax at steady-state at 1 mg QD.”