Crysvita: which tox species, and why?

“Hence, rabbits and cynomolgus monkeys were used in the in vivo nonclinical studies.”

“it was shown to bind with similar binding affinity (KD~10-11 M) to human, cynomolgus monkey and rabbit FGF23. KRN23 shows no binding to mouse, rat or dog FGF23.”

“A murine anti-FGF23 antibody at doses of 0, 3, 10 and 30 mg/kg was administered by SC injection twice a week for 2 weeks, or as a single dose, to male wild-type (WT) mice (C57BL/6J) and male hypophosphatemic (Hyp) mice (B6.Cg-PhexHyp/J).”

“In repeat-dose toxicity studies in rabbits up to 14 weeks, and in adult and juvenile cynomolgus monkeys up to 40 weeks, a spectrum of effects related to the primary pharmacology of burosumab was observed.”

“The Applicant conducted an enhanced pre/post-natal development (ePPND) study in cynomolgus monkeys, evaluating the effects of dosing from the start of organogenesis (GD20) to late 3rd trimester.”

“No genotoxicity or carcinogenicity studies have been conducted by the Applicant; this is endorsed.”

“A murine anti-FGF23 antibody at doses of 0, 3, 10 and 30 mg/kg was administered by SC injection twice a week for 2 weeks, or as a single dose, to male wild-type (WT) mice (C57BL/6J) and male hypophosphatemic (Hyp) mice (B6.Cg-PhexHyp/J).”