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

“The lack of genotoxicity studies is considered justified according to ICH S6”

“2) ofatumumab is not pharmacologically active in rodents and so the standard carcinogenicity bioassays are unsuitable, 3) there is no scientific evidence to suggest that depletion of B cells by any other anti-CD20 therapeutics leads to cancer”

“While the high dose was a no-effect dose for adverse developmental effects, a no-effect dose for mortality and immune effects in offspring was not established because of the limited number of evaluable offspring at the low dose.”

“some safety pharmacology end points, such as cardiovascular and renal parameters and body temperature, were evaluated as part of the pivotal 4 week and 7 month repeat dose toxicity studies in cynomolgus monkeys.”

“The lack of genotoxicity studies is considered justified according to ICH S6”

“The lack of genotoxicity studies is considered justified according to ICH S6”

“The lack of genotoxicity studies is considered justified according to ICH S6”

“The Division agreed with the sponsor that a standard assessment of carcinogenic risk was not required because ofatumumab is not pharmacologically active in rodent species.”

“The Division agreed with the sponsor that a standard assessment of carcinogenic risk was not required because ofatumumab is not pharmacologically active in rodent species.”

“There were no treatment-related changes in heart rate or QT interval in either investigation at doses up to 100 mg/kg.”