Nicox’s NCX 470 Shows Retinal Cell Protection in a Nonclinical Model

Nicox reported new data on NCX 470 in a nonclinical model of retinal cell damage induced by endothelin-1 (ET-1). NCX 470, Nicox’s lead clinical candidate, is a nitric oxide-donating prostaglandin analog currently in phase 3 clinical development for lowering IOP in patients with open-angle glaucoma or ocular hypertension. 

Elevated IOP is the main risk factor in glaucoma, however a variety of IOP-independent risk factors, including ischemia, contribute to damage of the optic nerve head and the retina, ultimately causing vision loss. The exploratory nonclinical studies reported today investigated the potential protective effects of NCX 470 on the retina and the optic nerve head. The results suggest that NCX 470 improves ocular perfusion and retinal function in damaged eyes compared to vehicle and therefore may have therapeutic properties over and above lowering of IOP.

Nonclinical experiments were performed to determine the effect of NCX 470 on ocular vascular reactivity and retinal function after repeated topical ocular dosing in a well-defined model of ischemia/reperfusion injury to the optic nerve in rabbits induced by ET-1. ET-1 alone was administered twice-weekly for 2 weeks, followed by concomitant dosing with NCX 470 or vehicle for a further 4 weeks.

Twice-weekly dosing with ET-1 increased ophthalmic artery resistivity after 2 weeks (P<0.05 vs. baseline), and this continued to increase during the next 4 weeks in the vehicle group to approximately 40% of baseline at week 6. This detrimental effect was significantly reversed in eyes co-administered with NCX 470 0.1% twice daily (P<0.05 vs. vehicle at week 6).

In addition, ET-1 dosing resulted in a marked decline in photoreceptor responses, which continued in eyes treated with vehicle. The decline was almost completely reversed by week 6 in eyes treated with NCX 470 (P<0.05 vs. vehicle).