NeoVista Epi Retinal Strontium 90 Treatment for AMD Update 3

During the 2008 Retina Society Meeting, held last weekend, NeoVista, Inc. provided eighteen-month data from its Phase II feasability study of the company’s novel beta radiation epi-retinal therapy for the treatment of the wet form of age-related macular degeneration (AMD). The long-term data from the study, which was initiated to test the safety and efficacy of their therapy when used in conjunction with Avastin (bevacizumab), showed a marked advancement in mean visual acuity results at month 18, while only a limited number of patients required additional injections of Avastin.

The data were presented at the Retina Society Meeting by Nelson R. Sabates, MD, Professor and Chairman, Department of Ophthalmology, University of Missouri-Kansas City (UMKC) School of Medicine and the lead investigator in NeoVista's ongoing Phase III study, CABERNET (CNV Secondary to AMD Treated with BEta RadiatioN Epiretinal Therapy).

"The data released demonstrate that NeoVista's concomitant approach has the potential to offer patients a less frequent treatment option that is just as effective, if not more effective, than the current standard of care," said Dr. Sabates. "It's highly encouraging to continually see patient outcomes improving as the study progresses."

"We're very delighted with the latest data from our Phase II study, as not only did the visual acuity improve in our patients over the long-term, but very few patients received additional injections as well," said John N. Hendrick, President and CEO of NeoVista. "The ultimate pledge of this therapy continues to be demonstrated as the long-term data hold promise in minimizing the treatment burden both for patients and physicians, not to mention the overall financial burden for the healthcare system."

NeoVista's revolutionary therapy applies a targeted dose of beta radiation to the leaking blood vessels that affect central vision; concomitantly, two injections of an anti-vascular endothelial growth factor (anti-VEGF) agent are delivered to maximize the acute therapeutic response. Preliminary data show that NeoVista's targeted radiation therapy can be safe for both the patient and the physician, and may be able to restore the patient's vision. The current standard of care for wet AMD requires persistent injections of anti-VEGF drugs for an indefinite period.

The ongoing multicenter feasibility study enrolled 34 trial participants (with a mean age of 72 years) from June 2006 to April 2007 at two centers in Brazil and one in Mexico. These patients, with predominantly classic, minimally classic, or occult (with no classic) choroidal neovascularization (CNV), received a single 24 Gy treatment of NeoVista's epiretinal brachytherapy in combination with two intravitreal injections of Avastin, one dose prior to or at the time of radiation delivery and another one month later, depending on which arm of the trial the patient was enrolled in. Additional therapy was delivered based upon the investigator's evaluation of disease activity.

Analysis of 18-month follow-up on the first 25 trial participants to reach that milestone, as shown in Graph 1 below, shows a mean improvement in visual acuity of 10.7 letters using the Early Treatment Diabetic Retinopathy Study (ETDRS) test; 96 percent of patients lost 15 letters or fewer, 76 percent gained some letters, 44 percent gained 15 or more letters, and 8 percent gained 30 or more letters. Of particular interest, 68 percent of the patients in the study did not require additional injections of Avastin throughout the 18-month period and the average number of additional injections within this subset was only 2.4 injections by month 18.


Graph 1

The visual acuity data after 18 months compares favorably with the results reported after 12 months, as shown in Graph 2 below. (This graph compares the Epi-Rad treatment without Avastin (purple color), with Epi-Rad plus Avastin (blue color) and the Marina (green) and Anchor (red) studies, which both used Lucentis.)

Graph 2

For more information on the NeoVista Epi-Retinal treatment, and for further information on the Marina and Anchor Studies, see my three earlier reports on NeoVista, posted November 19, 2007; July 11, 2007; and February 14, 2007.

Most of the limited number of adverse events were related to the vitrectomy procedure (retinal tear, retinal detachment, subretinal hemorrhage, and vitreous hemorrhage), rather than the epiretinal brachytherapy. To date, no instances of radiation toxicity have been reported by the Doheny reading center.

In contrast to other forms of radiation therapy for wet AMD, NeoVista's approach delivers the peak dose of energy directly to the lesion without damaging the normal retinal vasculature. Utilizing strontium 90, the focused energy is delivered to a target area up to 3 mm in depth and up to 5.4 mm in diameter. Importantly for patients, the systemic exposure to radiation is minimal, as the effective dose to the entire body from NeoVista's epiretinal device is less than that from a typical chest x-ray.

With the continued promise of these Phase II trial results, NeoVista continues to enroll patients in the company's pivotal trial, CABERNET. CABERNET is a multicenter, randomized, controlled study that will enroll 450 subjects at 45 sites worldwide, evaluating the safety and efficacy of NeoVista's epiretinal brachytherapy delivered concomitantly with the FDA-approved anti-VEGF therapy Lucentis (ranibizumab) versus Lucentis alone.

NeoVista Epi retinal Strontium 90 Treatment for Wet AMD

In my attempt to keep readers of this web site apprised of potential new treatments for age-related macular degeneration, I would like to present early positive results for a brand new treatment for AMD. The new vice president of sales & marketing at NeoVista, Tony Moses, an old friend, sent me a copy of the presentation of the recently presented first results for using strontium 90 in combination with a VEGF drug to alleviate vision loss in wet AMD. With his permission, here are the facts to date.

On January 16, 2007, Dr. Andrew Schachat, Vice Chair for Clinical Affairs, Vitreoretinal Department of the Cole Eye Institute, presented the first data on NeoVista’s Epi-Rad 90 Ophthalmic System at the Hawaiian Eye meeting (RHEM). The procedure involves the epi-retinal application of strontium 90 radiation for the treatment of wet AMD. A review of some of the early findings from his presentation are reported below.

Radiation treatment for AMD

NeoVista, Inc., of Fremont, Calif, released data demonstrating a potential benefit of treating wet AMD with radiation using the company's Epi-Rad 90 Ophthalmic System. Clinical data was presented from 2 separate feasibility studies that utilized the NeoVista product. The first study, involving a total of 24 patients, comprised 2 different doses of radiation (15 Gy and 24 Gy) delivered to the retina. The second study, which involved 20 patients, utilized a concomitant approach of 24 Gy radiation plus Avastin, where an injection of the drug was administered at the time of radiation treatment and an additional injection administered 30 days later. This is the approach the company plans to follow when it begins its pivotal 450-patient CABERNET trial this year. The company will utilize Lucentis instead of Avastin in this trial.

The Procedure and Early Results

The procedure involves performing a partial vitrectomy under local anesthesia. The delivery of the radiation takes between 3 and 5 minutes, depending on the calibration certification for the device being used, while the total procedure takes about approximately 40 minutes. The focal radiation penetration is about 3 mm into the choroid. The company claims that the ionizing radiation has a toxic effect on local pro-inflammatory and fibroblast cell populations, permanently disabling the proliferating CNV Cells.

In the two feasibility studies, using radiation alone, the lower dosage test (15 Gy) was not impressive, showing a loss in visual acuity after 9 (-2.4 letters) and 12 months (-3.2 letters).The study utilizing a higher dosage of strontium 90 (24 Gy) had better results, showing an increase in visual acuity after 9 (+5.6 letters) and 12 months (+7.6 letters). This compared favorably with the MARINA study of Lucentis, which had an increase of +7.2 letters after 12 months.

However, the second study, which utilized a concomitant approach of 24 Gy radiation plus Avastin, where an injection of the drug was administered at the time of radiation treatment and an additional injection administered 30 days later, was even more impressive. After only 2 and 3 months followup, the 20 patients showed an increase in VA of +14.2 and +14.9 letters, beating the MARINA study results by a wide margin.

Eugene de Juan, Jr., MD, the Jean Kelly Stock Professor of Ophthalmology at the University of California San Francisco and the inventor of the NeoVista treatment approach, commented, "Although the follow-up period (3 months) is relatively short, the results observed from the concomitant trial are extremely encouraging. The percentage of patients who improved in visual acuity by greater than 3 lines was reported at 50%, which is far above the 34% that was reported in the Lucentis MARINA Study. Granted, the NeoVista sample size is much smaller than that garnered from MARINA, but the evidence does support a closer investigation of this concomitant approach."

"We continue to see vision stability, and in many cases, vision improvement after just one treatment," stated John Hendrick, President and CEO of NeoVista. "The potential impact of our technology will greatly benefit patients, physicians, and the overall health care system. We will soon begin our Pivotal Trial incorporating concomitant use of Lucentis and Epi-Rad 90 therapy. The encouraging results observed in our concomitant feasibility trial have us excited about the future of this approach."

CABERNET Trial Design

According to the company, the CABERNET trial will involve 450 patients, with 300 receiving the 24 Gy dosage of strontium 90 plus Lucentis, and the control arm of 150 patients will receive Lucentis only. The study, to begin later this year, is scheduled to be held at 30 sites worldwide, 20 in the U.S. and 10 OUS. We will keep you informed on more details of the new trial as we learn them.

Questions & Answers

After reviewing Dr. Schachat’s Powerpoint presentation, I asked several questions of the company’s Vice President of Marketing & Sales, Tony Moses. Here are my questions and his responses:

1. Isn't even a partial vitrectomy more invasive than just the injection used for Lucentis/Avastin?

Any vitrectomy is naturally more invasive than an injection. What is not known, and what concerns many physicians is the potential outcome of numerous intraocular injections over time.

2. The higher dose appears to work better than the lower dose (duh!), but with a higher percentage of adverse results. Are there other dangers from the higher radiation dosage to the retina?

The only noticeable adverse effects in either group is the number of cataracts caused by our procedure, which is still in line with that reported by Lucentis in their MARINA data. To date (and we now go out to 18 months with some patients) there are no other significant adverse effects to report. Physicians are still concerned with the potential of causing radiation retinopathy, although we have seen no such cases yet.

3. How often does the treatment have to be repeated? (I don't think I saw that in looking quickly at the presentation.)

In our current data set, no patients have required a second procedure and we have strong belief in duration effect out past two years. We have this belief from reviewing the data from the initial sub-retinal approach to this procedure, first attempted by Dr. Eugene de Juan in 2003.

4. Your results with using both strontium 90 + Avastin appear to be additive. Perhaps that is the way to go?

You are absolutely correct! This is our approach going forward in our CABERNET Trial. Surgery plus one Lucentis injection at the time of surgery and then one booster injection at day 30 post-op.

5. Do you have an estimate of the cost? How will it compare, say, to a year's treatment with Avastin?

We estimate that our procedure will cost roughly $6,000 over a two year period, exclusive of the drug cost. To compare it to Avastin will be difficult since we have no data on the number of annual injections required to temper the disease. If we use Phil Rosenfeld's data from PrONTO, the number is roughly 6 per year. At $50 per injection (typically paid by the patient) plus the cost of injecting the drug ($200 for 2007) the Avastin cost will total ~$1,500 per year, not counting the cost of all exams. Please keep in mind that even though the patient may not require monthly injections, they must still be seen every 4 to 6 weeks to confirm disease stability. And, since the drug is not curing the disease, patients will likely have to continue this approach on an ongoing basis. This is one of our potential benefits - less burden on both the patient and the physician.