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

“No genotoxicity studies have been performed for lanadelumab in accordance with ICHS6. This is considered acceptable.”

“The conduct of carcinogenicity studies in rodents was not feasible based on the development of ADA in SD rats after repeated dosing. Based on the results of the 39-week study in monkeys as well as evidence from the available scientific literature, chronic inhibition of bradykinin production via DX-2930 treatment is unlikely to affect carcinogenic risk in HAE patients.”

“In the ePPND study in pregnant cynomolgus monkeys administered once weekly doses of 10 or 50 mg/kg (highest dose tested), there were no lanadelumab-related effects on pregnancy and parturition, embryo foetal development, survival, growth, and/or postnatal development of offspring.”

“Standard safety pharmacology endpoints were incorporated into the repeat-dose toxicology studies in rats (CNS) and cynomolgus monkeys (CV and respiratory).”

“No genotoxicity studies have been performed for lanadelumab in accordance with ICHS6. This is considered acceptable.”

“No genotoxicity studies have been performed for lanadelumab in accordance with ICHS6. This is considered acceptable.”

“No genotoxicity studies have been performed for lanadelumab in accordance with ICHS6. This is considered acceptable.”

“Shire submitted a written assessment of the carcinogenic potential of lanadelumab (DX-2930) in place of conducting rodent carcinogenicity studies.”

“The conduct of a 2-year carcinogenicity study with DX-2930 in rodents was not feasible based on the evidence for development of neutralizing anti-drug antibodies in SD rats after repeated dosing for 4 weeks.”

“ECG data was collected by Jacketed External Telemetry in the 4-week and 6-month SC monkey toxicity studies. There was no evidence for DX-2930-related effects on ECG parameters”