Cinqair: what was done before first-in-human, and what came after?

“This product has been used in Europe in an initial phase 1 single dose, dose escalation trial for treatment of 32 subjects with severe asthma (I96-350).”

“This product has been used in Europe in an initial phase 1 single dose, dose escalation trial for treatment of 32 subjects with severe asthma (I96-350). Doses ranged from 0.03 mg/kg to 1.0 mg/kg.”

“Standard toxicological evaluations were conducted after intravenous administration of 0, 1, 5, 25 mg/kg in monkeys every 4-weeks for 6-months (total of 7 doses) with 3-month recovery period. A similar dosing schedule of 28-days for a total of 7 doses was used for administration of 0, 2, 5, 25 mg/kg reslizumab in mice.”

“In toxicology studies up to 6 months duration, no target organs of toxicity were identified in either mice or monkeys at an IV dose up to 25 mg/kg once every 4 weeks.”

“Reproductive and developmental toxicology studies were conducted in CD-1 mice (fertility, embryo-fetal development, and pre-natal/post-natal development) and New Zealand rabbits (embryo-fetal development).”

“No effects on fertility or development parameters were identified at doses up to 50 mg/kg IV; exposure margins of approximately 6-fold were available in the mouse studies.”

“Reproductive and developmental toxicology studies were conducted in CD-1 mice (fertility, embryo-fetal development, and pre-natal/post-natal development) and New Zealand rabbits (embryo-fetal development).”

“The applicant conducted a 26-week study in Tg.rasH2 mice to assess the carcinogenic potential of reslizumab.”

“A transgenic mouse (Tg.rasH2) carcinogenicity study was conducted with dose concurrence by the Executive Carcinogenicity Assessment Committee (ECAC). No drug-related neoplasms were found after dosing up to 500 mg/kg IV once every two weeks.”

“Carcinogenicity: A 6-month carcinogenicity study was conducted in HRAS transgenic mice, a confirmed pharmacologically relevant mouse strain.”