Abstract
Purpose :
NCX 1741 is new chemical entity comprising NO and PDE5 inhibitory properties. This compound was shown to effectively lower IOP in various animal models of ocular hypertension and glaucoma. Herein we compared the IOP-lowering effects of NCX 1741 to that of travoprost, a known IOP-lowering prostaglandin F2alpha analog, in non-human primates with laser-induced ocular hypertension.
Methods :
Female laser-induced ocular hypertensive non-human primates (OHT-monkeys, n=6-7 eye/group) were used. NCX 1741 and travoprost were dissolved in suitable preclinical formulations and instilled (30μL) in the conjunctival pocket in a masked, crossover fashion. IOP was measured by pneumatonometry prior to dosing and up to 24 hours post-dosing.
Results :
Mean baseline IOP was similar for travoprost (IOP=32.9±3.8 mmHg) and NCX 1741 (IOP=32.4±3.4 mmHg). NCX 1741 lowered IOP starting at 0.5h post-dosing reaching maximum efficacy between 5h and 8h (IOP change, -6.3±2.6 and -5.8±1.3 mmHg at 5h and 8h post dosing, respectively) returning almost to baseline at 24h (IOP change, -2.3±1.1 mmHg). Conversely, travoprost had a slow onset of action starting to significantly decrease IOP 3h post dosing (IOP change, -7.5±1.9 mmHg) to then remain effective throughout the entire experimental period (IOP change, -7.5±1.3 and -8.0±2.8 mmHg at 8h and 24h post-dosing, respectively).
Conclusions :
NCX 1741 effectively lowered IOP in OHT-monkeys in a head-to-head comparison with travoprost. In addition, NCX 470 demonstrated a faster onset of IOP-lowering effect compared to travoprost making it a promising potential candidate for future clinical development.
This is a 2020 ARVO Annual Meeting abstract.