Investigational drug omidenepag 0.002% (Santen) significantly lowers intraocular pressure (IOP) in patients with ocular hypertension or primary open-angle glaucoma when administered once or twice daily, according to phase 2 data. However, twice-daily dosing produces a much higher rate of adverse events.

“An active metabolite of omidenepag is a selective, nonprostaglandin, prostanoid EP2 receptor agonist, which has been shown to lower IOP by increasing aqueous outflow via both conventional and uveoscleral pathways,” said Kenneth W. Olander, MD, PhD, in a news release. “This contrasts with the prostaglandin F receptor agonists, which predominantly decrease IOP by uveoscleral outflow. Other phase 2 studies have demonstrated that omidenepag 0.002% is the optimal dose for phase 3 study. The aim of this 6-week multicenter dose-finding study was to examine if the efficacy and safety profile of omidenepag 0.002% twice-a-day dosing was superior to once-a-day dosing in eligible patients.”

For this randomized, phase 2, US-based multicenter study, 98 patients aged 18 and older with a diagnosis of ocular hypertension or primary open-angle glaucoma were randomized to treatment with omidenepag isopropyl 0.002% administered in each eye once daily (n=50) or twice daily (n=48). After a washout period of ≤4 weeks, participants initiated their assigned omidenepag therapy. Intraocular pressure was measured at 8:00 am, 12:00 pm, and 4:00 pm at baseline and at weeks 2 and 6.

Baseline mean diurnal IOP (± standard deviation) was 25.4±2.9 mmHg in the twice-daily group and 24.6±1.9 mmHg in the once-daily group. The least squares mean diurnal IOP (± standard error) at week 6 was 17.77±0.43 mmHg with twice-daily administration and 18.37±0.41 mmHg with once-daily administration. There was no significant difference between the 2 groups in least squares mean IOP change at any time point.

Adverse events were about 3 times more common with twice-daily application, at 41.7% in the twice-daily group, compared with 14% in the once-daily group. In addition, 5 patients in the twice-daily group discontinued early, 4 due to adverse events that included ocular hyperemia, iritis, nausea, conjunctival hyperemia, and ocular discomfort. There were no early treatment discontinuations in the once-daily group.