Safety and pharmacokinetics of intravitreally repeatedly injected panitumumab in non-human primates - a study performed under good laboratory practice.

BACKGROUND

Epidermal growth factor (EGF) has been suggested to play a role in myopic axial elongation, and EGF receptor blockade may be of potential therapeutic benefit. Here we examined the ocular and systemic toxicity of panitumumab, a clinically used EGF receptor blocker in oncology, when repeatedly administered intravitreally in non-human primates.

METHODS

The experimental study included six non-human cynomolgus primates (3 males) which underwent five (n = 1 animal) or three (n = 5 animals) 4-weekly intravitreal injections of panitumumab (dose: 0.78 mg (78µL)) or of phosphate buffered solution (PBS) (78µL).

RESULTS

The study group with panitumumab injections consisted of 7 eyes and the control group with PBS injections of 5 eyes. Two animals of the study group developed on Day 59 (two days after the third injection) signs of a slight intraocular inflammation (cells in anterior chamber and vitreous) and reduction of intraocular pressure, with most of the signs having resolved at study end (Day 86). Panitumumab reached the serum peak concentration at 24 h after the first dose (Cmax 18.3 to 946ng/mL; serum exposure 2120 to 37300 h*ng/mL). Four weeks after the third injection (Day 86), panitumumab concentrations in aqueous humor ranged from 12.8 ng/mL to 65.0 ng/mL, and in the vitreous from 1.74 ng/mL to 531 ng/mL, with a panitumumab accumulation factor between 0.891 and 0.012. TUNEL staining did not reveal pathological results.

CONCLUSIONS

Except for mild and reversible intraocular inflammation in some eyes, repeated intravitreal application of 0.78 mg panitumumab did not result in ophthalmological or systemic adverse effects in non-human primates.