Bimatoprost insert offers noninvasive platform for early glaucoma patients

Reviewed by James Brandt, MD

A 19-month, open-label study of a novel bimatoprost, sustained-release ocular insert shows good safety and efficacy. The insert is polymer ring that sits atop the eye in the conjunctival fornix. Phase III trials are expected to begin in 2017.

“There will clearly be a number of platforms for sustained release delivery of ocular drugs reaching the market over the next five to 10 years,” said James Brandt, MD, professor of ophthalmology and director, glaucoma service, University of California Davis, Sacramento, CA. “This platform is noninvasive and is ideally suited for the patient who has early glaucoma and you do not want to put at any additional risk.”

Dr. Brandt, who was lead author of the study, presented the mid-term results of an extension study of the topical ring (Bimatoprost Ring, ForSight Vision5).

Researchers extended the original 6-month randomized controlled trial for an additional 13 months as an open-label study.

The device is an inert polymer ring which elutes an effective daily dose of about 7 mcg  of bimatoprost at 6 months. The ring is not bioabsorbable and is designed to be replaced by a clinician every 6 months. The open-label extension trial provided for 3 successive replacements of the device.
 

Early glaucoma patients

“The vast majority of people being treated with eye drops and other methods to lower IOP have very mild and early glaucoma,” Dr. Brandt explained. “These are the patients in whom you generally do not want to be injecting or implanting devices into the eye.”

In patients with early glaucoma or early hypertension, safety must be the priority, he said.

"The more invasive platforms look potentially  effective, but with the potential of higher risk of complications to the patient,” he added. "This platform is essentially noninvasive. [It is] a flexible ring which sits on the eye and can be removed at any time.”

The ring is manufactured in multiple sizes. The flexible device is inserted beneath the upper lid and moved into the interior cul-de-sack with a scleral depressor or a cotton swab. The insert seats itself in the fornix with one or two blinks. Patients can feel the insert in place for a few days, but nearly all reported the device is comfortable or not bothersome.

Retention, safety profile

Retention, safety profile

During the initial 6-month study, 88.5% of the devices remained in place, with 94.7% retention during the extension period. There were no cases in which the patient was not aware that the ring had become dislodged.

Patients in the initial trial were randomly assigned to either the bimatoprost insert plus artificial tears or an inert ring plus timolol 0.5% eye drops. Patients in the bimatoprost arm showed a consistent 4 mm Hg to 6 mm Hg reduction in IOP.

At the end of the initial study, patients were eligible to continue for another 13 months and two successive device replacements. Patients in the timolol arm in the initial study used the bimatoprost insert during the open-label extension.

Both the patients who continued using the ring and those who switched to the ring showed a sustained reduction in IOP of 4 mm Hg to 5 mm Hg when the inserts were replaced as designed out to 19 months.

A total of 115 patients completed the initial study. Because of the approval timing for the extension study, some patients completed the first study before the extension began. A total of 75 patients enrolled in the extension. Of this initial group, 65 completed the first 7-month extension and 63 completed the entire 13-month extension.

The safety profile out to 19 months was good, Dr. Brandt reported, and consistent with data from earlier phase I and phase II data. Treatment emergent adverse events were consistent with bimatoprost exposure, including conjunctival hyperemia (21.3%), eye discharge (21.3%), punctate keratitis (16%), increased lacrimation (13.3%), blurred vision (12%), eye puritis (10.7%), foreign body sensation in the eyes (8%), ocular discomfort (8%), dry eye (6.7%), and eye irritation (6.7%).

The only ocular serious adverse event was decreased visual acuity in a patient who developed a cataract not related to treatment.

“The main issue with sustained-delivery platforms is balancing safety with efficacy,” Dr. Brandt said. “While some of the more invasive sustained delivery platforms look to be very safe in a controlled clinical trial, there is an underlying risk of infections and other complications which increases with the invasiveness of the platform, especially in the real world.

“If you look at the universe of patients being treated with pressure-lowering medications, the vast majority have early glaucoma or early ocular hypertension, he added. In these patients, glaucoma is a relatively slowly progressing disease. The last thing you want to do is place a patient at risk of a complication when they have little risk of ever being impaired by glaucoma.”

James Brandt, MD

E: jdbrandt@ucdavis.edu

Dr. Brandt is the lead author on the results for the Bimatoprost Ring extension study.