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New technologies on horizon to redefine drug delivery


Glaucoma has an adherence problem. Drugs that are highly efficacious are far less than optimally effective because patients fail to take eye drops properly or don’t take them all. Novel drug-delivery technologies could improve adherence and outcomes.

Glaucoma has an adherence problem. Drugs that are highly efficacious are far less than optimally effective because patients fail to take eye drops properly or don’t take them all. Novel drug-delivery technologies could improve adherence and outcomes.

“In glaucoma, the only delivery method we have seen is the eye drop,” said L. Jay Katz, MD, professor of ophthalmology, Thomas Jefferson University; director of Glaucoma Service, Wills Eye Institute, Philadelphia. “We have to work on different types of technologies, new molecules, new systems to create better ways of getting drugs to the appropriate structures of the eye that will change the course of glaucoma.”

Katz co-moderated an overview of “New Horizons in Drug Delivery” as part of the New Horizons Forum at the 2017 Glaucoma 360 meeting with Cheryl Rowe-Rendleman, PhD, CEO and managing consultant, Omar Consulting Group. The session highlighted six companies developing new drug delivery systems.


Envisia Therapeutics

Envisia Therapeutics has leveraged 3-D printing technology developed in the microelectronics industry to create customized delivery vehicles for prostaglandins and other ophthalmic agents. The company’s PRINT technology produces sheets of biodegradable nanometer-scale containers that can be injected intracamerally to provide prostaglandin efficacy 24/7 for up to six months from a single dose.

“Think of it as nanotechnology meets formulation science,” said Benjamin Yerxa, PhD, president. “We can dial in the precise performance attributes needed for an agent that is very transferable to a commercial manufacturing environment.”

Phase II studies with travoprost show intraocular pressure (IOP) lowering similar to travoprost ophthalmic solution 0.004% (Travatan Z, Alcon Laboratories). There have been no serious adverse events over 11 months of an ongoing safety trial and less hyperemia than topical prostaglandin analogues.

The same biodegradable delivery vehicle shows linear release of dexamethasone for diabetic macular edema over 6 months. Another project shows good results with 90-day extended release of aflibercept (Eylea, Regeneron).

“Back of the eye extended release for large and small molecules is becoming reality,” Yerxa said.

Eximore Technologies


Eximore Technologies

Eximore Technologies is taking a less invasive route with drug-eluting punctal plugs that are removed and replaced every three to six months. The system has been used with prostaglandin analogues and beta blockers in glaucoma and lipids, nonsteroidal anti-inflammatory drugs (NSAIDs) and immunosuppressives for dry eye.

“We are here to take efficacy out of the hands of patients and solve the adherence problem,” explained Ishay Attar, co-founder and CEO. “Using proprietary nanotechnology, up to 40% of the plug by weight is active drug that diffuses into the eye at a steady, controlled rate. The plug is invisible once in place, comfortable, retained very securely, can administer multiple drugs at once, and preservative free.”

Animal studies with a latanoprost-loaded plug show a 50% reduction in IOP. A second product for dry eye is in the preclinical stages. The company plans to launch human trials outside the United States later this year.

Graybug Vision

Graybug is developing an injectable platform, encapsulating novel agents in microparticles that form a resorbable drug depot in the vitreous. Initial dosing will be every six months, but recent animal data support once-yearly dosing.

“Adherence is the major problem in glaucoma,” said Jeffrey L. Cleland, PhD, president and CEO. “Within the first few months, patients stop taking their drops, but can’t tell that their ocular pressure is up and don’t start to lose vision right away. Our technologies take adherence out of the hands of the patient and put it in the hands of the doctor.”

Graybug is developing two related technologies. One is an injectable drug depot that can be tuned for different agents, different delivery sites within the eye, and different delivery durations.

The second is novel forms of familiar drugs that have been optimized for depot delivery. It is possible to deliver a prostaglandin-timolol combination, for example, or an IOP-lowering agent plus a neuroprotective agent.

The company plans to launch its first clinical trial in wet age-related macular degeneration over the summer and its first glaucoma trial in 2018.

Contact lens delivery


Contact lens delivery

Researchers at Harvard University are developing a drug-eluting contact lens. A drug-eluting polymer film is attached to the periphery of a standard hydrogel contact lens to provide controlled release directly to the ocular surface. Lenses can be removed and replaced by the patient every 30 days to provide a steady state drug delivery for as long as needed.

Latanoprost-eluting contact lenses provided steady state delivery for 30 days in animal studies. Work in glaucomatous monkeys showed nearly double the IOP reduction using latanoprost-eluting contact lenses compared to latanoprost drops.

“We were surprised by these results,” said Joseph B. Ciolino, MD, associate professor of ophthalmology, Massachusetts Eye and Ear Clinic, Boston. “We are planning a human pilot study to explore the possibility that if you deliver drug in a sustained manner, you may get better pressure reduction than you can with drops. The technology is simple and it resonates with glaucoma specialists and patients who already use bandage contact lenses.”

Mati Therapeutics

Mati Therapeutics is taking a different approach to punctal plug delivery. Its Evolute plug is inserted intranasally to improve retention and the active drug is housed in a core that offers a constant surface area to control the rate of drug dispersal. The device is designed for up to 120 days of use, depending on the drug and the condition to be treated.

The company already has conducted multiple phase II trials in glaucoma, ocular hypertension, and allergy. Glaucoma trials using latanoprost have shown a consistent 5 mm Hg to 5.5 mm Hg reduction in IOP. Preclinical data show the system can elute travoprost faster than latanoprost and produce 1 mm Hg to 3 mm Hg greater reduction in IOP.

“Considering that travoprost is more potent than latanoprost, the potency difference is key when you are delivering microgram amounts,” said Christopher A. Muller, chief commercial officer. “We are planning clinical trials with travoprost and fully expect to get better IOP reduction than we are seeing with latanoprost.”

Ocular Therapeutix


Ocular Therapeutix

Best known for ocular sealant ReSure, Ocular Therapeutix is in late-stage development of drug-eluting intracanalicular inserts to deliver dexamethasone for post-surgical pain and inflammation, allergic conjunctivitis, and travoprost for glaucoma. Earlier stage inserts are being studied in dry eye and retinal vascular diseases. Retinal disease inserts are injected into the back of the eye.

The company resubmitted its New Drug Application for Dextenza, its dexamethasone insert, after dealing with manufacturing issues. If approved as expected in 2017, Dextenza could be the first drug-eluting intracanalicular insert on the U.S. market. Glaucoma is next.

The company is enrolling patients for phase III trials of QTX-TP, its travoprost-eluting insert, for glaucoma and ocular hypertension. The insert behaves much like Dextenza and is designed to last 90 days before replacement.

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