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

“The lack of genotoxicity testing was considered acceptable, as in accordance with the ICH S6 guideline, the range and type of genotoxicity studies routinely conducted for pharmaceuticals are not applicable to biotechnology-derived pharmaceuticals and therefore are not needed.”

“The CHMP also considered acceptable that no carcinogenicity testing was performed, taking into account the lack of an appropriate animal model, the well-established risk of indirect tumorigenicity caused by prolonged immunosuppression”

“When alemtuzumab was administered to pregnant huCD52 transgenic mice during organogenesis (gestation days [GD] 6–10 or GD 11–15) at intravenous doses of 3 or 10 mg/kg, no teratogenic effects were observed. However, there was an increase in embryolethality”

“No dedicated safety pharmacology studies were conducted by the applicant.”

“The lack of genotoxicity testing was considered acceptable, as in accordance with the ICH S6 guideline, the range and type of genotoxicity studies routinely conducted for pharmaceuticals are not applicable to biotechnology-derived pharmaceuticals and therefore are not needed.”

“The lack of genotoxicity testing was considered acceptable, as in accordance with the ICH S6 guideline, the range and type of genotoxicity studies routinely conducted for pharmaceuticals are not applicable to biotechnology-derived pharmaceuticals and therefore are not needed.”

“The lack of genotoxicity testing was considered acceptable, as in accordance with the ICH S6 guideline, the range and type of genotoxicity studies routinely conducted for pharmaceuticals are not applicable to biotechnology-derived pharmaceuticals and therefore are not needed.”

“The CHMP also considered acceptable that no carcinogenicity testing was performed, taking into account the lack of an appropriate animal model, the well-established risk of indirect tumorigenicity caused by prolonged immunosuppression and the previous scientific advice provided by the CHMP.”

“The CHMP also considered acceptable that no carcinogenicity testing was performed, taking into account the lack of an appropriate animal model, the well-established risk of indirect tumorigenicity caused by prolonged immunosuppression and the previous scientific advice provided by the CHMP.”

“Cardiovascular effects were observed in both studies at doses of 30 mg/kg, but the effects were only seen in a single animal per study. With respect to the ventricular premature complexes seen in one animal in the repeat-dose study, the CHMP acknowledged that this observation could be a normal variant in cynomolgus monkeys and therefore not treatment-related.”