Abstract
Purpose:
ONO-9054 (Ono Pharmaceuticals, Osaka Japan) is a novel dual FP/EP3 agonist prodrug under development for the treatment of ocular hypertension and glaucoma. The purpose of this study was to investigate the effect of ONO-9054 on intraocular pressure (IOP) in normotensive monkeys during and after 7-day repeated ocular administration and compare the extent of IOP lowering to that produced by latanoprost, travoprost, bimatoprost, and tafluprost.
Methods:
IOP lowering effects of ONO-9054 (30 μg/mL), latanoprost (50 μg/mL), travoprost (40 μg/mL), bimatoprost (300 μg/mL), and tafluprost (15 μg/mL) were examined in male cynomolgus monkeys. Drops were administered topically in a 30μL volume once into each eye for 7 days. IOP was measured with an applanation pneumatonometer just before and at 4, 8, 12, and 24 hours after ocular administration on days 1, 4 and 7 as well as at 48 and 72 hours after the last administration.
Results:
ONO-9054, latanoprost, travoprost, bimatoprost, and tafluprost caused IOP reductions at 4, 8, 12, and 24 hr after application on days 1, 4, and 7. The maximal IOP reductions achieved with ONO-9054 (5.8 ± 0.7, 6.6 ± 0.7, and 7.3 ± 0.8 mmHg on days 1, 4, and 7, respectively) were greater than those achieved with latanoprost (3.4 ± 0.6, 4.6 ± 0.5, and 4.9 ± 0.4 mmHg), travoprost (4.0 ± 0.5, 4.9 ± 0.5, and 5.1 ± 0.6 mmHg), bimatoprost (1.9 ± 0.4, 3.1 ± 0.4, and 4.0 ± 0.5 mmHg), or tafluprost (3.5 ± 0.8, 4.3 ± 0.7, and 4.6 ± 0.7 mmHg) on the same days. Furthermore, ONO-9054 showed longer-lasting IOP-reducing effects following the last dose on day 7.
Conclusions:
The IOP-lowering effects of the FP/EP3 agonist ONO-9054 were more potent and longer-lasting than those produced by any of the marketed FP receptor agonists. The possibility that the dual FP/EP3 receptor agonist ONO-9054 may produce a similar advantage in IOP lowering for patients with ocular hypertension or glaucoma is currently under investigation in a phase 2 clinical trial.
Keywords: 568 intraocular pressure