Prototype has potential for retinal diseases

Santa Barbara, CA-An implantable, refillable pump for intraocular drug delivery (Ophthalmic MicroPump, Replenish Inc.), currently in the prototype stage, has potential applications that include treatment of glaucoma as well as several retinal diseases currently treated with frequent intravitreal injections.

The device also may be useful for neuroprotection, according to Robert L. Avery, MD, a retina surgeon in Santa Barbara, CA, who also is active in ocular research.

Mark S. Humayun, MD, PhD, and engineering colleagues at the University of Southern California, Los Angeles, and the California Institute of Technology, Pasadena, CA, initially developed the device. Preclinical, proof-of-concept testing of prototypes was performed using glaucoma medications, and phase I clinical trials of the device for the treatment of glaucoma and also age-related macular degeneration (AMD) are scheduled to begin.

The pump's reservoir ranges from 60 to 300 µl, which can store several months worth of glaucoma or AMD drugs for the eye, according to Sean Caffey, MD, chief executive officer of Replenish. Despite the large supply, Dr. Caffey added, "We believe the [device] is the world's smallest, refillable, implantable drug pump."

A number of retinal diseases also are candidates for drug delivery with the implantable pump. The results of several recent studies showed that therapy targeting vascular endothelial growth factor (VEGF) was effective in treating both branch and central retinal vein occlusion; these findings are likely to lead to much greater use of this therapeutic approach, Dr. Avery said. Similarly, anti-VEGF therapy appears to be effective in treating diabetic macular edema, as shown by the recent http://www.DRCR.net trial results.

"In the retina world, we need to be able to live with these large molecules, and this is a type of delivery device that will allow for the delivery of these molecules," Dr. Avery said. Work he and his colleagues have performed with ranibizumab (Lucentis, Genentech) suggests that it will be stable for months at body temperature.

Dry AMD is another disease in which intraocular drug delivery through the miniature pump could be utilized, said Dr. Avery, who is participating in a trial of Fab fragment inhibitor-complement factor D for the treatment of this disease.

"[The mini-drug pump] certainly could be useful in a disease process that takes place over many years that we might have to inhibit with large molecules," Dr. Avery said.

Design applications

The design feature of the pump that permits delivery of a lower dose of medicine over an extended period also is an important feature in its potential applications. Monthly injections, which many studies to date have suggested are necessary for ongoing therapeutic efficacy in certain retinal diseases, require administration of a large quantity of medication, while the total amount of medication needed could be much less if given daily.

"By delivering lower doses we can use less drug and also minimize the side effects," he said.

The mini-drug pump system also could be adaptable for individualized therapy, with the amount of medicine increased or decreased depending on the degree of change or stability in the patient's eye, Dr. Avery said.

"Those of us who treat these patients know there's a lot of variability in their VEGF-driven demand and their need for anti-VEGF therapy," he said.

Dr. Avery also said that the research and development activities associated with the pump include a closed-loop device for glaucoma. This device would include a pressure transducer for measuring IOP. When the pressure surpasses a designated level, the device would send a message triggering an injection.