Spinraza: which tox species, and why?

“Based on the intended patient population (neonates to adolescents), 14- and 53-week repeat dose toxicology studies were conducted in juvenile cynomolgus monkeys using IT dose administration.”

“Since humans are the only species known to have the SMN2 gene, in vivo pharmacology was examined in mouse models of SMA in which the endogenous mouse gene has been removed and the human SMN2 gene is expressed.”

“In vivo studies (using intracerebroventricular and intrathecal [IT] administration) were conducted in transgenic mouse models of SMA because only humans are known to have the SMN2 gene.”

“Toxicity studies of nusinersen were conducted in mice and juvenile cynomolgus monkeys.”

“Developmental and reproductive toxicity studies in mice and rabbit showed no fetal effects related to treatment with nusinersen.”

“Administration of nusinersen (0, 5, 15, or 50 mg/kg) to male and female mice by subcutaneous injection, once every two weeks for 2 years, resulted in an increase in the incidence of vascular tumors (combined hemangioma and hemangiosarcoma) at the highest dose tested.”

“In vivo studies (using intracerebroventricular and intrathecal [IT] administration) were conducted in transgenic mouse models of SMA because only humans are known to have the SMN2 gene.”