ABSTRACT
Title
NCX 434, a novel nitric oxide (NO)-donating triamcinolone acetonide analog shows long lasting activity in the VEGF-induced leakage model of diabetic macular edema in rabbits
Authors
F. Impagnatiello1,C. De Nardi1, S. Brambilla1, V. Chiroli1 , AH Krauss2, G. Prasanna2 and E. Ongini1
1NicOx Research Institute, Bresso, Milan, Italy
2Department of Ocular Biology, Pfizer Inc, San Diego, CA.
1NicOx Research Institute, Bresso, Milan, Italy
2Department of Ocular Biology, Pfizer Inc, San Diego, CA.
Abstract
Diabetic macular edema (DME) is mainly treated with anti-vascular endothelial growth factor (anti-VEGF) agents or intravitreal (IVT) glucocorticoids. Glucocorticoids and, in particular, triamcinolone acetonide (TA), are highly effective drugs but they require repeated monthly injections and significantly enhance the risk of hypertensive glaucoma in patients. To address these issues we synthesized a novel NO-donating TA analog which was later shown to enhance oxygen saturation in non-human primate optic nerve head when administered IVT and to be devoid of IOP raising effects.
Here we further explored the efficacy on macular edema of NCX 434 over time using the VEGF-induced leakage model in New Zealand white rabbits and monitored its residence time in the vitreous compared to TA.
The IVT injection of NCX 434 (6.0 mg/eye) inhibited VEGF-induced retinal leakage up to 90 days post dosing more effectively than reference TA administered at equimolar doses in rabbits. Consistent with that, significant amount (20% of the injected dose) of NCX 434 was still detectable in the vitreous of NCX 434-treated eyes 90 days post-dosing while TA was below the limit of quantification at the same time point.
The present data further indicate that NCX 434 is as effective as TA but its activity last longer than that of TA when tested in a rabbit model of diabetic macular edema. These and previous findings make this an important new therapeutic opportunity to be further explored for the treatment of macular edema.
Here we further explored the efficacy on macular edema of NCX 434 over time using the VEGF-induced leakage model in New Zealand white rabbits and monitored its residence time in the vitreous compared to TA.
The IVT injection of NCX 434 (6.0 mg/eye) inhibited VEGF-induced retinal leakage up to 90 days post dosing more effectively than reference TA administered at equimolar doses in rabbits. Consistent with that, significant amount (20% of the injected dose) of NCX 434 was still detectable in the vitreous of NCX 434-treated eyes 90 days post-dosing while TA was below the limit of quantification at the same time point.
The present data further indicate that NCX 434 is as effective as TA but its activity last longer than that of TA when tested in a rabbit model of diabetic macular edema. These and previous findings make this an important new therapeutic opportunity to be further explored for the treatment of macular edema.