Drug Reservoir to Enter Clinical Trials

Episcleral Drug Reservoir Poised to Enter Phase I/II Clinical Trials

by Matt Hasson from Ocular Surgery News
Volume 27 - Number 19, October 10, 2009

The tiny silicone device, inserted under the conjunctiva, diffuses medication through the sclera and into the eye to treat retina and vitreous diseases. A new episcleral device may revolutionize the sustained delivery of medication to treat many debilitating retinal conditions, according to a researcher.

The episcleral drug reservoir is designed to deliver safe and sustained doses of medication directly to the retina and vitreous to treat age-related macular degeneration, diabetic retinopathy, uveitis, endophthalmitis, retinoblastoma and other conditions.

"The main clinical advantage will be, using this drug delivery system, we can get much more drug into the posterior segment of the eye," A. Linn Murphree, MD, told Ocular Surgery News. "It's not like the drug inserts that have been used in the past. It is simply a carrier system for any formulation of sustained-release drug formulation that one would like to put in to deliver it posteriorly."

The device is designed to deliver any drug, such as steroids, antibiotics, chemotherapy agents and anti-inflamatories, he said.

Pre-clinical animal testing is complete, and phase I/II clinical trials are scheduled to begin next year.

Dr. Murphree, director of the Retinoblastoma Program in The Vision Center at Children's Hospital Los Angeles, discussed the device at the Association for Research in Vision and Ophthalmology Summer Eye Research Conference on Ophthalmic Drug Delivery Systems in Bethesda, MD.

Dr. Murphree is developing the device in conjunction with Ricardo Carvalho, MD, PhD, and 3T Ophthalmics.

Prolonged, Direct Diffusion

The episcleral drug reservoir, placed under the conjunctiva and attached to the sclera, allows gradual diffusion of a drug through the sclera and inward to the retina and vitreous, Dr. Murphree said.

"In fact, it's the same concept as drops in that it's passive diffusion, the drug going through the eye," he said. "The main difference is that in drops and injections around the eye, the contact time with the ocular surface is very low. That is, the drops are washed away quickly. Things injected around the eye are carried away by the lymphatics and blood vessels into the systemic circulation. This delivery system simply sequesters the drug in contact with the sclera, so that it has time - hours, days, weeks - to diffuse slowly into the interior of the eye."

There is no membrane intervening between the drug and sclera, so the drug is in direct contact with the sclera. The drug is sealed in the reservoir and does not leak or get washed away, Dr. Murphree said.

"The key here is maintaining the concentration gradient across the eye wall," he said. "That is the huge, simple advantage of this delivery system."

Dr. Murphree said the device may one day be an alternative to intravitreal injections and eye drops. In children with retinoblastoma, it may eliminate systemic delivery of chemotherapy drugs, which often cause side effects such as secondary infection.

In patients with AMD, it may replace intravitreal injections, which require frequent office visits and pose various risks, such as vitreous hemorrhage and retinal detachment, according to a press release from The Vision Center.
 

Looking Ahead to Clinical Trial

In preclinical animal studies, the episcleral drug reservoir delivered 30 to 40 times more drug into the interior of the eye than traditional periocular injections, Dr. Murphree said.

The silicone device is not expected to cause patient discomfort or disrupt normal vision.

"It's very small," he said. "It's made out of the same material that scleral buckles are made of. There's no reason it should not be tolerated extremely well."

The phase I/II clinical trial will assess safe drug formulations and doses for a group of retinoblastoma patients, he said.

"We think that for dose findings, that is, determining which does is safe, probably 25 eyes would be enough to arrive at that dose, Dr. Murphree said. "We will be using two drugs, and they will be put on either separately, one reservoir per eye, and then, once we know what is safe and tolerated, there will be one of each placed on the eye."

Treated eyes will be those that would otherwise be enucleated, Dr. Murphree said.