New glaucoma drug delivery devices home in on compliance

New Orleans-Patient compliance (and non-compliance, as the case may be) is nothing new when discussing glaucoma.

Nor are the multiple devices and systems previously developed or under investigation with the hope of improving compliance, said Richard Lewis, MD, speaking at Glaucoma Day at ASCRS 2016.

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“We’ve been talking about compliance for as long as I can remember,” Dr. Lewis said. “And we’ve been trying to address the issue for just as long a time. Alternatives to eye drops were described as early as 1976, with the Ocusert implant.”

Ocusert was basically pilocarpine in a delivery system put into the lower cul-de-sac. The issue with the system was that it first delivered too much medication, which led to side effects, and then when the system delivered too little medication, there was little drug effect, he said.

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“The problem was there were complications that sometimes couldn’t be overcome and it wasn’t a very successful product commercially,” he said. “But the problem of patient compliance with traditional topical medications has not dissipated. We need better medications delivered for a longer duration.”

A potentially viable option to deliver drugs is through punctal plugs, but “they have to be retained in the eye and that’s been an obstacle,” Dr. Lewis said.

At issue are the higher retention rates needed to ensure punctal plugs remain commercially viable.

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“The disadvantages beyond retention are directional flow and topical effect,” he said.

Too many earlier versions would end up in the nasal area instead of the eye, Dr. Lewis said.

Showing promise

Showing promise

But two newer devices are showing promise, Dr. Lewis noted.

Mati Therapeutics is developing a punctal plug delivery system, as is Ocular Therapeutix. Mati purchased the delivery technology from QLT in 2013 and uses latanoprost.

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Ocular Therapeutix’s Dextenza is a sustained-release dexamethasone intracanalicular depot currently in phase III studies for allergic conjunctivitis, a phase II study for inflammatory dry eye disease, and is awaiting regulatory approval for the treatment of postoperative inflammation and pain. Dextenza has been developed to deliver a 4-week tapered release, the company has said, and once the therapy is complete, the hydrogel resorts and exits through the nasolacrimal system without need for physician removal.

“They’re currently working on using travoprost in a punctal plug,” Dr. Lewis said.

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Mati’s device is a solid core, while Dextenza conforms to the punctuation, “so there may be a higher retention rate,” Dr. Lewis said, noting both companies claim higher than 95% retention rates. Dextenza changes color if it falls out, which may also alert patients if the device has dislodged. And both companies claim drug duration effects of about 3 months.

Alternatives to punctal plugs are also being developed, including drug-eluting contact lenses.

“These are non-invasive, have no preservatives, a steady elution rate,” he said.

According to the literature, a latanoprost-eluting contact lens has been developed by encapsulating latanoprost films in methafilcon by ultraviolet light polymerization.

“So far, there’s only animal data, but it’s a good idea and they’re claiming increased compliance will be a reality. In vitro studies show there’s about a 24-day duration,” Dr. Lewis said.

Gel drops

Finally, there are gel eye drops, but this technology is “still very investigational and also not yet in humans.”

The concept is that the drops form a stable gel that releases the medication over the course of a month, Dr. Lewis said.

In rabbit data, the gel appeared to be non-irritating, and was completely retained for the study duration (28 days).

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“That’s got a lot of potential, and may be good for specific types of treatment, but it may not be an ideal vehicle in glaucoma,” he said.

Researchers are also evaluating the subconjunctival inserts.

“These are non-biodegradable polymers that can be safely removed,” he said.

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Benefits include that they’re preservative-free and are targeting a 12-month duration of effect.

“It’s still a work in progress and it’s unclear if these will be able to achieve adequate pressure reduction using a prostaglandin,” he said.

The ongoing challenge for all of these systems and device is zero order (rate of elimination is constant and does not depend on or vary with the drug intake or plasma concentration of the drug), and that not all the alternatives are ideal for all medication (prostaglandins in particular where it is unclear if prolonged exposure on the ocular surface is good or bad for pressure reduction).

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Finally, these types of studies are time consuming and typically last years. They’re also costly-even when investigating an already approved drug. And there may be unintended consequences-“the Ocusert moved across the cornea,” Dr. Lewis said.

Most of the data available on the devices and drug delivery systems has been presented at ophthalmic meetings, but there is “not a lot of data available in the peer-review journals yet,” he said.

Dr. Lewis is a consultant for Aerie Pharmaceuticals, Alcon Laboratories, Allergan, Carl Zeiss Meditec, Glaukos, Ivantis, Oculeve, and PolyActiva. He is also chief medical officer for Aerie Pharmaceuticals.