Ocular hypotensive effect of the novel EP3/FP agonist ONO-9054 versus Xalatan: results of a 28-day, double-masked, randomised study

Abstract

Background/aimsONO-9054 is being developed for the reduction of intraocular pressure (IOP) in patients with ocular hypertension (OHT) and open-angle glaucoma (OAG). This study compared the novel dual EP3/FP agonist ONO-9054 with the FP agonist Xalatan.MethodsAdults (n=123) with bilateral mild/moderate OAG or OHT, with unmedicated IOP of ≥24 mm Hg at 8:00 hours, ≥21 mm Hg at 10:00 hours and ≤36 mm Hg, were randomised 1:1 to receive ONO-9054 (0.003%, 30 μg/mL) or Xalatan (0.005%, 50 μg/mL) once daily for 28 days.ResultsDay 29 mean diurnal IOP was −7.2 mm Hg for ONO-9054 vs −6.6 mm Hg for Xalatan. At 08:00 hours, the IOPs were comparable, and at all later time points the decrease in IOP was greater for ONO-9054. On day 29, the odds of a mean IOP reduction of ≤−25%, ≤−30% and ≤−35% for ONO-9054 were 2.39, 2.37 and 4.85 times more, respectively, than the odds for Xalatan (p<0.05, post hoc analyses). The percentage of subjects achieving target IOPs on day 29 (≤17, ≤16 and ≤15 mm Hg) was greater for ONO-9054 than for Xalatan; the odds of achieving an IOP ≤15 mm Hg for ONO-9054 were 2.4 times more than the odds for Xalatan (p<0.01, post hoc analysis).ConclusionsSubjects randomised to receive ONO-9054 were more likely to achieve a greater per cent reduction in IOP and were more likely to achieve target IOPs than those receiving Xalatan. The effects of ONO-9054 in reducing IOP appear to persist longer than those of Xalatan.Trial registration numberNCT02083289, Results.

Topical Medication Therapy for Glaucoma and Ocular Hypertension

“…The morning (AM) and evening (PM) dosage of 30 μg/ml ONO-9054 have similar sustained reduction in IOP, whereas the incidence of hyperemia and dryness is slightly increased in the patients subjected to the PM dose of ONO-0954 ( Berlin et al, 2016 ). Miller Ellis, et al observed that ONO-9054 (30 μg/ml) has a better IOP lowering effect than Xalatan once daily ( Miller Ellis et al, 2017 ). The rate of the mean IOP reduction of ≤ −25%, ≤ −30%, and ≤ −35% in the ONO-9054-treated patients is 2.39, 2.37, and 4.85 times higher than the rate in the Xalatan-treated patients, and 2.4 times more patients achieve an IOP ≤15 mmHg than those treated with Xalatan ( Miller Ellis et al, 2017 ).…”

Effect of Cromakalim Prodrug 1 (CKLP1) on Aqueous Humor Dynamics and Feasibility of Combination Therapy With Existing Ocular Hypotensive Agents

“… 14 , 20 New glaucoma drugs (e.g., adenosine receptor agonists and modified prostaglandin analogs) purportedly targeting the conventional outflow pathway are being tested in various preclinical and clinical trials in the United States. 21 – 36 However, even these newer drugs show a host of adverse side effects, ranging from conjunctival hyperemia and pain at the site of instillation, to events like headache and oropharyngeal pain. 21 , 26 , 28 , 37 Because of this, and because over time patients usually become refractory to topical glaucoma medications, continued search for the development of therapeutics with a unique mechanism of action and reduced or nonexistent side effect profile is a significant need for clinicians treating glaucoma.…”

Prostaglandin analogues and nitric oxide contribution in the treatment of ocular hypertension and glaucoma

“…Several studies tested this compound in healthy volunteers, as well as in ocular hypertensive and normotensive glaucoma patients (Harris et al ., ). The compound was generally found to be well tolerated, and when compared with latanoprost in phase 2b studies, ONO‐9054 achieved a slightly greater diurnal mean IOP reduction (−7.2 and −6.6 mmHg, for ONO‐9054 and latanoprost, respectively) (Miller Ellis et al ., ).…”

“…From this class, the most advanced is omidenepag isopropyl (DE‐117), which is being co‐developed by Santen and Ube Industries and is currently in phase 3 clinical trials. Likewise, the EP 3 /FP receptor agonist, ONO‐9054, is currently being developed by Santen and ONO Pharmaceutical for the reduction of IOP in patients with ocular hypertension and glaucoma (Miller Ellis et al ., ).…”