Medical Device Daily Contributing Writer

POIPU BEACH, Hawaii — The Hawaiian Eye Meeting, which takes place here on one of the Islands each year in mid-January, has become a highly-regarded event for ophthalmologists and industry. This year attendance was once again at record levels, with more than 1,400 ophthalmologists registering.

The meeting generally attracts specialists from two critical areas of ophthalmology today — the cataract and refractive surgery specialist, by far the largest category of ophthalmic doctors and retinal specialists, whose prominence has surged in recent years.

The reason for the upswing in prominence for retinal physicians relates to the introduction of several new medications for the treatment of age-related macular degeneration (AMD), which has dramatically improved the outcomes for elderly patients suffering from this disease.
As its name implies, AMD is associated with aging, afflicting 18% of those between 70 and 74 years old, surging to 47% among people 85 years and older. It is a chronic, progressive disease of the macula, the central part of the retina, causing irreversible loss of central vision and the No. 1 cause of severe vision loss and blindness among those over age 50 in the developed world.

Prior to 2000, there were essentially no effective treatment options for halting or reversing the course of AMD, which causes a horrid decline in an elderly person’s quality of life. However, since that time, three new pharmaceutical agents have reached the U.S. market, producing vast improvement in patient outcomes.

In particular, Lucentis, a potent anti-VEGF agent introduced by Genentech (South San Francisco) in mid-2006, has had an enormous impact on the treatment of AMD. Its clinical trials have not only demonstrated that Lucentis can stop the progression of the disease but that in a significant number of patients it has been shown to actually reverse its progression and substantially improve visual acuity.

With 200,000 new cases of late stage (wet) AMD diagnosed annually in the US alone, the market opportunity for newer, possibly better or less costly approaches to remain fertile. In a session titled “Treatment of Neovascular AMD: Other Options” at the “Retina 2007” section of this meeting, a highly promising and relatively new technology was discussed by Andrew Schachat, MD, who is the vice chairman of Clinical Affairs, Vitreoretinal Department at the Cole Eye Institute, Cleveland Clinic Foundation (Cleveland, Ohio). The technology, developed by privately-owned, venture capital-backed NeoVista (Fremont, California) features the use of an ionizing radiation source that delivers strontium-90 directly to the macula.

The current device has two components, a reusable strontium-90 applicator and a multi-channel tester. Strontium-90 is attached to the distal end of a guidewire built within the device and a lever extends the wire to the cannula tip and then retracts within a housing post-therapy. The company intends to introduce the product with a disposable tip at the time of commercial launch to ensure a completely sterile procedure and reduce the amount of reprocessing time within the operating room. The multi-channel tester is used for source verification prior to each treatment. The goal of this therapeutic device, trade-named the EPI-Rad Ophthalmic System, is to permanently disable the proliferating new cells — the culprits in causing central visioin loss — by damaging their DNA structure.

The procedure itself is minimally invasive, since performed under local anesthesia during a partial vitrectomy, a common surgical procedure performed by retinal specialists, and taking only about 30-45 minutes in total treatment time. The radiation is delivered at a controlled penetration depth of about 3 mm, with the EPI-Rad focal therapy irradiating the treatment area.

Schachat presented the data from three relatively small feasibility trials that have been completed so far. Two trials were conducted using just strontium-90 at two different dosage levels while the third trial incorporated the use of an anti-VEGF agent Avastin as part of the protocol.
The first trial showed solid results, comparable to the results of the gold standard Lucentis in its early months, but then the benefits trailed off. The second trial, using a higher strontium-90 dose, showed better durability and even more promise. Most intriguing, however, were the results of the third pilot trial, which incorporated two Avastin injections along with the irradiation process, one at the time of radiation treatment, the other at day 30 post-op.

In this study, which followed 20 patients for three months, there was dramatic improvement in visual acuity, with a mean gain of nearly 15 letters read on a visual acuity chart. This compares extremely favorable to the approximately six letters gained at three months reported from Genentech’s pivotal MARINA trial, which supported its New Drug Application FDA approval.

There appear to be several potential advantages of the NeoVista approach. A key advantage, assuming its benefits are durable, is that it will be far more convenient for most patients, who are now required to continue a monthly regimen of Lucentis injections for many months or even years.

Even more importantly it could slash the overall cost of treating AMD. Each monthly Lucentis injection costs the healthcare system about $2,200 (drug cost plus the physician injection fee), including a monthly patient out-of-pocket, co-pay cost of $400 — an annual cost of about $26,000 per patient, with the out-of-pocket annual cost approaching $5,000.

Meanwhile, the Medicare reimbursement system faces a potentially enormous financial burden, with thousands of patients being treated at $2,200 per month. For this reason, many ophthalmologists are using Genentech’s Avastin, a “sister” drug to Lucentis for treating AMD.

Avastin, a larger molecule variety of Lucentis — FDA-approved for various cancers — has shown anecdotal efficacy and safety for treating AMD off-label. Its huge off-label use, which was confirmed by a straw poll of retinal specialists at this meeting, is being driven solely by its cost, about $50 per dose when used to treat AMD. By comparison, a Lucentis injection costs $1,950.

Indeed, off-label use has become so rampant that the National Eye Institute (Bethesda, Maryland) has decided to fund a large trial that will compare the safety and efficacy of the two Genentech agents. This two-year trial, called Complications of Age-Related Macular Degeneration Treatment Trials (CATT), is slated to begin in April 2007.

NeoVista is planning to commence its pivotal clinical trial in the U.S., beginning in the second quarter of 2007, with the goal of completing the trial in about one year.

The main features of this trial, dubbed the CNV Secondary to AMD Treated with Beta Radiation Epiretinal Therapy (CABERNET) trial, is that it will be conducted at roughly 30 sites worldwide (20 in the U.S.) and will randomize patients to either strontium-90 plus Lucentis or to just Lucentis. A total of 450 patients will enter the trial, 300 on the NeoVista arm and 150 in the Lucentis arm.

Elias Reichel, MD, vice chair for research and education, Department of Ophthalmology at Tufts New England Medical Center (Boston) told Medical Device Daily: “The NeoVista system is extremely promising and could become a very important and valued addition to our AMD treatment options. I am eager to see the results from the pivotal trial.”

Reichel, an experienced AMD specialist, is an advisor to the company, and Tufts is expected to be one of the clinical sites for the CABERNET study.

NeoVista, which was founded in 2002 by The Innovation Factory (Duluth, Georgia), has been funded by a group of venture capital firms since its inception. The company closed on a $41 million venture capital round in December 2006, which will be used to complete the company’s pivotal trial and begin commercialization.