Novel dexamethasone formulation shows efficacy and safety with once-daily use

September 1, 2020

A vehicle-controlled phase 2 study investigating once- and twice-daily administration of a novel, preservative-free topical formulation of dexamethasone as treatment for pain and inflammation after cataract surgery met its primary endpoints.

Results of a phase 2 trial suggest that dexamethasone cyclodextrin nanoparticle ophthalmic suspension 1.5% mg/mL (OCS-01, Oculis), a novel topical formulation of dexamethasone, has the potential to become the first once-daily and preservative-free topical corticosteroid for treating pain and inflammation after ocular surgery, said Eric D. Donnenfeld, MD, at the 2020 ASCRS virtual meeting.

Donnenfeld reported results from the SKYGGN study that randomly selected 153 patients 1:1:1 to treatment with OCS-01 once daily, OCS-01 twice daily, or vehicle for 14 days. The study met its primary endpoints analyzing absence of anterior chamber cells at postop day 15 and absence of ocular pain at postop day 4. There were no efficacy differences between the two OCS-01 dosing regimens and both were safe and well-tolerated.

“Inflammation and pain remain expected consequences of ocular surgery. Although available topical steroids are effective for treating these sequelae, potency and compliance with products that need to be used several times a day are major issues,” said Donnenfeld, a SKYGGN investigator who is clinical professor of ophthalmology, New York University Langone Medical Center, New York, and Founding Partner, Ophthalmic Consultants of Long Island and Connecticut, Garden City, NY. “Using a novel and proprietary nanoparticle formulation, OCS-01 was developed to deliver a potent anti-inflammatory effect and excellent safety profile with once-a-day dosing.”

Donnenfeld noted that the concentration of dexamethasone in OCS-01 is 15-fold greater than that found in commercially available topical dexamethasone suspension. In addition, the novel vehicle used for OCS-01 increases ocular surface residency time to hours compared with minutes using conventional dexamethasone 0.1% suspension. Furthermore, the proprietary nanoparticle technology enhances penetration of the active ingredient. As another benefit, the formulation is preservative-free.

SKYGGN design and outcomes

A total of 20 US centers participated in the SKYGGN study. Patients were eligible for enrollment if they had an anterior chamber cell score ≥ 2 at their first postoperative visit 18 to 30 hours post-uncomplicated cataract surgery and a pin-hole ETDRS visual acuity without any other correction that was >20 letters (approximately 20/400) in the operative eye and >35 letters (approximately 20/200) in the fellow eye. Follow-up visits were scheduled at postoperative days 4, 8, 15, and 22.

The three study groups were similar at baseline in their demographic characteristics, and 148 patients completed the study. Mean age of patients across the three groups ranged from 66 to 68 years, approximately two-thirds of subjects were female, and the vast majority were Caucasian.

The percentage of patients with absence of anterior chamber cells on day 15 in the OCS-01 once daily, OCS-01 twice daily, and vehicle groups was 51.0%, 66.7%, and 19.6%, respectively (P<.0001 for both OCS-01 groups versus vehicle). Absence of pain on day 4 was achieved by 72.5% of patients treated with OCS-01 once daily and 45.1% of controls (P<.005). In the OCS-01 twice-daily group, 62.7% of patients were pain-free on day 4 (P=0.074 versus vehicle).

“Data on percentage of patients with absence of anterior chamber cells from earlier postoperative visits show a statistically significant difference favoring the once-daily OCS-01 group versus vehicle was achieved on day 8. The results for the pain assessment showed the proportion of patients who were pain-free increased in all groups as follow-up continued, but the difference was statistically significant between both OCS-01 groups and vehicle at days 8 and 15,” Donnenfeld said.

One patient in the vehicle group and one patient treated with OCS-01 twice daily withdrew from the study because of an adverse event. However, there were no significant ocular or systemic adverse events. Importantly, IOP ≥30 mm Hg was not observed in any patients at any follow-up visits nor did any patient have a ≥10 mm Hg increase from baseline IOP.

“The overall adverse event rate was higher in the vehicle group than in the OCS-01 groups, probably because the adverse events were procedure-related rather than treatment-related,” Donnenfeld said.

Donnenfeld noted that the potent activity, safety, and tolerability of OCS-01 observed in SKYGGN are consistent with results of another phase 2 trial investigating the novel steroid formulation as a treatment for diabetic macular edema. The latter study enrolled 144 patients and found a statistically significantly greater decrease in central macular thickness in patients treated with OCS-01 compared with vehicle-treated controls. There were no significant ocular adverse events in the OCS-01 group.

Eric D. Donnenfeld, MD
E: ericdonnenfeld@gmail.com
Donnenfeld is a consultant to Oculis.