Alhemo: which tox species, and why?

“The rabbit was selected as efficacy species, the Cynomolgus monkey was selected as the nonrodent safety species and both species were used in pharmacokinetic/pharmacodynamic (PK/PD) assessment.”

“Characterisation of concizumab binding to TFPI showed high affinity, sub-nanomolar binding to rabbit, NHP and human TFPI with similar binding constants (KD of 0.22 nM, 0.06 nM and 0.04 nM for rabbit, Cynomolgus monkey and human, respectively).”

“Toxicity studies of up to 52-week duration have been conducted in Cynomolgus monkeys with a normal coagulation system (non-haemophilic).”

“The cynomolgus monkey was selected as the non-rodent nonclinical safety species for repeat-dose toxicology and both species were used in pharmacokinetic/pharmacodynamic (PD) assessments.”

“Dedicated reproductive and developmental toxicology studies were not conducted as concizumab is primarily indicated for use in male patients with hemophilia and the clinical development program was conducted exclusively in males.”

“Concizumab is not functional in rodents and standard carcinogenicity studies have not been conducted.”

“Based on the pharmacology data and the lack of cross reactivity to rodent species, the rabbit was selected as the nonclinical efficacy species (hemophilia animal models).”