Ocular insert overcoming glaucoma treatment challenges

Take-home message: A bimatoprost-releasing ocular insert that rests in the conjunctival fornix (ForSight VISION5) lowered IOP in patients with ocular hypertension or glaucoma by an average of 4 to 6 mm Hg from baseline over 6 months.

By Cheryl Guttman Krader; Reviewed by James D. Brandt, MD

Sacramento, CA-Results of a multicenter, randomized, double-masked phase II study demonstrate that a novel topical ocular insert (Helios, ForSight VISION5) providing sustained delivery of bimatoprost safely and effectively reduces IOP for a period of 6 months, said James D. Brandt, MD.

The study enrolled 130 patients who were randomly assigned to placement of the bimatoprost ocular insert or twice-daily treatment with topical timolol maleate 0.5%. A double-dummy design was used to maintain masking so that the bimatoprost ocular insert group also received artificial tears twice daily and the timolol eye drop group underwent placement of a non-medicated insert.

The insert is an investigational product in the United States.

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Mean diurnal IOP calculated using measurements obtained at times 0, 2, and 8 hours at the 2-, 6-, and 12-week visits was assessed as the primary endpoint, and secondary endpoints analyzed mean diurnal IOP at 4, 5, and 6 months.

Throughout the study, the bimatoprost ocular insert group maintained clinically relevant reductions in diurnal IOP in the range of 4 to 6 mm Hg.

The novel treatment was well tolerated and had a safety profile consistent with topical bimatoprost, with no unexpected or unanticipated safety issues encountered.

“There is a pressing need for patient-independent, sustained delivery of medications to prevent blindness from glaucoma,” said Dr. Brandt, professor of ophthalmology and director, glaucoma service, University of California Davis, Sacramento, CA. “I am very excited about this platform that is well-retained, tolerated, and potentially gives the ability to deliver multiple medications using a single system.”

Device design

Speaking on behalf of the Bimatoprost Ocular Insert Investigators, Dr. Brandt described the design of the insert as being “remarkably simple.” The device is an “O”-shaped, non-biodegradable ring impregnated with bimatoprost without preservatives and releases an effective dose of bimatoprost at a predictable rate (~7 mcg/day) over a period of 6 months. The product, which is available in several sizes with diameters ranging from 24 to 29 mm, is easily inserted under the upper lid, and using a scleral depressor or similar instrument, the clinician places it into the inferior cul de sac.

“With a blink or two, the insert seats itself in the fornix and is comfortably in place,” Dr. Brandt said.

The eligibility criteria for the study were typical of those used for trials assessing IOP-lowering modalities. Patients were adults with open-angle glaucoma or ocular hypertension that was controlled or likely to be controlled with topical monotherapy. After a washout period, they had to have IOP ≥23 mm Hg at time 0, ≥20 mm Hg after 2 and 8 hours, and ≤34 mm Hg at all times.

Mean baseline IOP was about 25 mm Hg at time 0, about 23.7 mm Hg at 2 hours, and about 23 mm g at 8 hours. Contact lens wearers were excluded as were patients known to be intolerant or unresponsive to the study medications.

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“We also took advantage of a washout period to verify that patients could comfortably wear the insert,” Dr. Brandt said.

All patients wore a non-medicated insert during this time, and if needed, the size and fit of the insert could be adjusted before the start of the primary study, he noted.

“Arguably, the most important attributes of an externally delivered sustained-release system are that it can be retained comfortably and that patients realize if it becomes dislodged or falls out,” Dr. Brandt said. “In this study, ~90% of patients maintained the insert in place bilaterally without physician intervention for 6 months, and we encountered no cases of dislodgement where the patient was unaware of the incident.”

He also commented on the magnitude of IOP lowering achieved in the bimatoprost ocular insert group and the potential role for the insert in the treatment paradigm.

“Although the product did not meet the statistical definition of noninferiority to timolol, the study was underpowered relative to the observed treatment effects,” he said. “A phase III study with a significantly larger sample size is being planned.”

Prior studies show twice-daily dosing of prostaglandins being less effective than once-daily dosing.

“Our data similarly show somewhat less efficacy when the drug is delivered in a continuous manner,” Dr. Brandt said.

“Although this study compared the bimatoprost insert to topical timolol for regulatory reasons, in the real world we would expect it to be used in patients who cannot or choose not to take topical medications,” he said. “For that reason, we believe a 4 to 6 mm Hg drop in IOP is very significant.”

James D. Brandt, MD

E: jdbrandt@ucdavis.edu

This article is adapted from a paper presented by Dr. Brandt at the 2015 meeting of the American Academy of Ophthalmology. Dr. Brandt is a consultant to and receives grant support from ForSight VISION5. He is a consultant to Glaukos and Reichert and an equity owner in Glaukos.