Rituxan: which tox species, and why?

“For primary pharmacodynamics only experiments in non-human primates are relevant. Neither rodent nor canine B-cells bind rituximab.”

“such studies are unnecessary because B-cells in cynomolgus monkeys are lysed by a single dose of rituximab, which is evidence of relevant activity even if affinity and CD20 expression may be different in humans and primates.”

“Weekly dose of rituximab up to 20 mg/kg (= 276 mg/m2 ) was generally well tolerated over up to 8 weeks of treatment in a further GLP toxicity study in Cynomolgus monkeys.”

“Significantly, adverse reactions unrelated to the targeted effect were seen, neither in single nor in multiple dose studies in the Cynomolgus monkey.”

“A subsequent pre-and postnatal reproductive toxicity study in cynomolgus monkeys was completed to assess developmental effects including the recovery of B cells and immune function in infants exposed to rituximab in utero.”

“No long-term animal studies have been performed to establish the carcinogenic or mutagenic potential of RITUXAN or to determine potential effects on fertility in males or females.”

“For primary pharmacodynamics only experiments in non-human primates are relevant. Neither rodent nor canine B-cells bind rituximab.”