PHOTODYNAMIC THERAPY

Posted by Barb Porteous on April 15, 1999 at 11:40:03:

Does anyone have information on "visudyne" from an article by Dr.Neil Bressler @ Johns Hopkins University?

Posted by Dan Roberts on April 16, 1999 at 08:21:21:

Scientists are harnessing light beams to fight one of the most insidious problems of aging, providing a ray of hope against a creeping blindness that steals vision from the center out.

Age-related macular degeneration, or AMD, is the leading cause of blindness in people over 50. First, fine detail fades. Your crossword puzzle seems OK at a glance, until you try focusing on just one word. People's faces start to blur. You can't read or drive. Eventually, the worst form of AMD causes blindness.

Now scientists are trying an experimental light-activated drug to help preserve patients' eyesight. There is not a cure, cautioned Dr. Neil Bressler of Johns Hopkins University. Nothing can restore already-lost vision. But for early-stage patients, "we may be able to slow down vision loss, or reduce the chance of (AMD) costing any more vision," said Bressler, who heads a nationwide Visudyne study.

And the National Eye Institute, worried that the graying of America means millions more people are at risk, is pouring $25 million into research to curb the disease. Among the work:

1. An ongoing trial of 4,800 people is comparing whether vitamins or beta carotene or the mineral zinc can stop the progression of AMD-caused vision loss.

2. A government-funded study is about to enroll 350 people to see if a new type of surgery to remove a tuft of disease-caused blood vessels could stop the blindness.

3. In March, the government starts a third study to see if removing drusen--yellow deposits on the retina that are a precursor of AMD--from people's eyes can actually prevent the disease from ever striking.

AMD is a budding epidemic, warns institute director Carl Kupfer. Some 1.7 million sufferers are legally blind already, and the aging population means some 6 million more could go blind in 20 years.

The macula is the light-sensitive layer of tissue in the center of the retina. Two types of AMD destroy it:

1. "Dry" AMD, which accounts for 90 percent of cases, slowly breaks down the macula's light-sensitive cells. There is no treatment. But the damage occurs very slowly so victims only gradually notice a blind spot in their central vision and don't completely lose sight.

2. "Wet" AMD is rarer, but much worse. New blood vessels form behind the retina, leaking onto the macula and destroying it. First, straight lines appear wavy. Then sufferers suddenly develop a central blind spot that often progresses within two years.

The research focuses on wet AMD. There is one treatment, a laser that cauterizes the blood vessels. But only 15 percent of patients qualify because, if the blood vessels are in the wrong spot, the laser can hurt more than it helps.

Visudyne works differently. The light-activated drug is injected into the arm and then migrates into the eye's abnormal blood vessels. Shine in a non-burning beam of light and the drug "switches on," eliminating those blood vessels without hurting surrounding tissue.

In a study of 600 patients, 61 percent given Visudyne had stable or slightly improved vision after a year, vs. 45 percent of patients given a placebo. The study is continuing another year, important because more-rapid vision loss usually occurs in wet AMD's second year. Bressler expects approval to manufacture Visudyne by next year.

For now, people over 40 need regular eye exams, with their eyes dilated, to hunt early disease signs. AMD sufferers and those at risk should ask an ophthalmologist about new treatments, including studies like the eye institute's, Bressler advised.

A small radiology study presented last month suggests two weeks of low-dose radiation might help wet AMD, too, although Kupfer cautioned better studies are needed. And Kupfer warned AMD patients to beware dubious treatment offers like "blood filtering" that cost thousands of dollars but have little, if any, scientific backing. "It's a terrible indication of how people are grasping" at hope, he said.

Posted by Richard Davis, MD on April 20, 1999 at 11:59:44:

Dear Dan,
I wanted to respond regarding Dr. Kupfer's comments warning AMD patients to beware of "blood filtering" treatments that cost thousands of dollars. I think it is about time that Dr. Kupfer and the researchers and companies promoting photodynamic therapy for the treatment of AMD come clean and openly discuss the estimated costs of this therapy, as well as its potential long term effects.

First, let’s review the facts. For example, QLT Phototherapeutics makes one of the molecules Dr. Kupfer is referring to, Visudyne. QLT, like Miravant and others in the race for an effective treatment for Wet AMD, is a publicly-traded NASDAQ company whose stock value has recently soared on the news of Visudyne's "successful clinical trial" and its expected FDA approval process for the drug.

The research and development pathway for Visudyne has been associated with numerous risks, and the successful approval of Visudyne for QLT (and its backers, Ciba Vision and Swiss parent Novartis who have probably invested hundreds of millions of dollars in this new technology) means the difference between enormous success and colossal failure for the project. It is reasonable for them to expect a handsome return on their investment. From some industry sources, I have been told that they are telling their Wall Street analysts that they anticipate Visudyne selling for about $2,000 per treatment (based on interpreting analysts’ estimates of the company’s value).

The analysts do the math (5 year discounted cash flow projection) and they come up with a $1.3 billion dollar valuation for a company that has never sold the first vial of the drug. (And some people actually have the audacity to believe that Rheopheresis is “hyped”, go figure!)

In my opinion, what the well-paid researchers in the QLT research cadre don't emphasize enough is that photodynamic treatment effects only last about 8 weeks or so. In their much-publicized trial, an average of 3 to 4 treatments were found to be necessary each year to maintain the results. In some cases, as many as six treatments were required in a year. And this was only to maintain vision, not to substantially improve it.

In addition to just a projected $2,000 selling cost of the drug, one must consider the costs of the laser treatment, disposables and physician's fees. This produces a projected total cost probably somewhere in the $3,000 to $4,000 per treatment range. With three to six annual treatments required; well Dan, you can do the math. This is a classic annuity type drug/treatment mechanism that Novartis certainly hopes will make QLT the darling of Wall Street, and let’s be frank, ophthalmologists won’t be upset either. So from a strategic product management point of view, the technology has everything going for it. However, the ever-present competitive threat must be managed and OccuLogix represents an easy target.

One more thing that I believe is that QLT’s Management has failed to publicly emphasize the nature of the reimbursement methods in place from HCFA to obtain Medicare reimbursement for Visudyne, or any new drug or device for that matter. This process is traditionally long and arduous. Approval of new reimbursement codes take anywhere from 18 to 36 months after commercialization commences, depending upon numerous factors. So until then, even with FDA approval, the treatment will remain a private pay option for patients. I don’t think patients realize this, and it certainly has not been announced in any statement released that I have seen. And I follow the company very closely.

So if the approval study was correct, photodynamic therapy patients, and ultimately you and I under the Medicare system that we pay for, can expect to pay somewhere between $9,000 to $24,000 per year for the rest of the life of the patient. Given the average age of the patients (about 70 years) and their actuarial life expectancy (about 8 years), the total average costs per patient to maintain their vision (not improve it) can be calculated to be somewhere between $72,000 to almost $200,000! By stark contrast, the total projected costs of Rheopheresis treatments using the new RheoFilter MDF system over the same period are anticipated to only range from $25,000 to $45,000 – which is 75% less! So I ask you, which is actually the expensive treatment, and why is there so much disinformation over this issue?

Consider that Rheopheresis: (1) costs 50% to 75% less (on an annualized forward-looking projection); (2) maintains or improves vision for relatively twice as many patients (80% to 90%); (3) improves vision to a greater degree (average about 2 lines of ETDRS vision improvement); (4) has no side effects; (5) is historically safer than blood donation, and (6) is designed to treat AMD in its earliest stages (Dry AMD) - before the disease has a chance to progress to the more severe Wet condition where photodynamic technologies may have a benefit in those small number of patients with subfoveal neovascularization.

Also, it is important to remember that photodynamic therapy only treats the symptoms of Wet AMD disease, the neovascularization injury response. Unlike Rheopheresis, it is incapable of treating the intrinsic microcirculatory defect itself (hypothesized to be an etiologic component of the disease’s expression).

Please understand that we do not condemn their science, nor do we judge their motives, we simply think that it is time for the whole truth to be told. These critics have failed to tell the whole truth regarding costs and reimbursement. In addition, they publicly have failed to discuss the cumulative effects of repeated photodynamic treatments on the retina, or to even speculate on any potential long-term effects. My guess is that they really don’t know and will not know for some time. Considering the devastating effects of SRNV, this is probably OK. But none the less, these concerns, along with the huge costs involved, should be openly discussed in the general public news releases, like that made by Dr. Kupfer. Since statements like this fail to discuss these matters, I believe that the average patient would not be able to discern that any of these issues exist. And that is really unfair to frustrated AMD patients looking for answers.

With results of the MAC-1 Rheopheresis German trial now made public, and the Utah pilot study completed, companies preparing to market photodynamic technologies are most certainly feeling the pressure to put on a full court press to try to denounce the role of apheresis for the treatment of this disease.

OccuLogix is just a small company comprised of dedicated doctors and researchers who have bravely pioneered a novel technology that has hurt no one while improving the sight of hundreds of patients the world over. It is time that the technology is given a chance on a level playing field don't you think? The OccuLogix story is interesting. It is a classic case of David and Goliath. We intend to tell the story. We also intend to provide ophthalmologists with a technology designed to improve their patients' vision so that they can read it.

In closing, as my favorite 600 pound gorilla says: “Of course that’s just my opinion, I could be wrong.”

Sincerely,
Richard Davis, MD
Chairman, OccuLogix Corporation

• Rheopheresis® - OccuLogixSM Corporation, through its subsidiary Apheresis Technology, Inc. (ATI), is currently enrolling patients in a final phase multi-center clinical trial on Rheopheresis using Membrane Differential Filtration for the Treatment of Dry Age-related Macular Degeneration. For details.

Miravant studies

Posted by Jean LeComte on July 30, 1999 at 07:14:38:

My husband has Macular degeneration and has developed the "wet" in his best eye. The Retina Specialist has recommended the Miravant testing procedure and it seems to have some pitfalls. Has anyone been through this to give us an idea about pursuing this course of action. Thank you so much, Mrs.Jack leComte

Posted by Judi D. on August 03, 1999 at 16:08:08:

The Miravant Study is another photodynamic therapy project. There are differences between the Miravant drug (Purlytin) and the Ciba drug (Visudyne). Both are activated using low level laser light, thus treating only the leaking blood vessels and not damaging the surrounding healthy tissue.

Photopoint

Posted by Neicy on August 02, 1999 at 19:53:38:

My Father is going to New Orleans this week to see if he is eligibale for a phase 3 clinical study for photopoint therapy!! It sounds really scarry...does anyone have info?

Posted by Dan Roberts on August 03, 1999 at 11:41:00:

Dear Neicy,
Otherwise known as Photodynamic Therapy, this involves the use of a "cool" laser to coagulate blood in the retina, which is less damaging than current treatment. A coagulating drug (Visudyne) is injected into the blood vessels, and it is activated by the light beam.

I hope your father will be accepted into the study, and that he can be helped by this treatment.

Best wishes,
Dan

Posted by Dan Roberts on September 17, 1999 at 09:34:43:

Here is an article which will give you the information on Photodynamic Therapy.

QLT AND CIBA VISION ANNOUNCE POSITIVE RESULTS FOR VISUDYNE™ (VERTEPORFIN) THERAPY FOR WET AGE-RELATED MACULAR DEGENERATION

VANCOUVER, CANADA and ATLANTA, GA - QLT PhotoTherapeutics Inc. (QLT) and CIBA Vision Corporation-the eye care unit of Novartis AG-announced today that Visudyne™ (verteporfin) therapy has been shown to preserve vision in a significant number of patients with the "wet" form of age-related macular degeneration (AMD), the leading cause of blindness among people over the age of 50. These findings are based on an initial 12-month analysis of 24-month pivotal Phase III studies using verteporfin, now referred to by the brand name Visudyne. The treatment is part of an emerging new platform technology known as photodynamic therapy and is being co-developed by QLT and CIBA Vision.

Results of the TAP (Treatment of AMD with Photodynamic therapy) Investigation, which comprises two randomized, double-masked, placebo-controlled trials involving 609 patients at 22 centers in North America and Europe, showed that patients treated with Visudyne therapy were more likely to have stable vision (defined as a loss of less than 3 lines of vision on a standard eye chart) or improved vision compared to placebo-treated patients at 12-month follow-up. These results were found to be statistically significant for each of the two studies, as well as for the combined data (p=0.0002).

Based on these positive 12-month results, QLT and CIBA Vision anticipate filing for regulatory approval of Visudyne therapy in the U.S., Canada, and Europe in 1999.

This study remains ongoing in order to determine longer-term efficacy and safety. As this therapy is still investigational, only patients who are currently enrolled in these clinical trials are eligible for treatment at this time.

"Today's announcement is a significant breakthrough in the efforts to find a treatment for a widespread disease that has grown into a major public health concern," said Dr. Neil M. Bressler, Chair of the TAP Study Advisory Group, and a retinal specialist and Professor of Ophthalmology at the Wilmer Eye Institute of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

"We are indebted to the hundreds of patients who are continuing to participate in these trials and to all the investigators for their efforts in carrying out such a landmark study. Visudyne therapy offers new hope for potentially preserving the vision and independence of the hundreds of thousands of individuals who will be diagnosed with wet AMD each year," said Dr. Bressler.
 
Study Data:

Based on an intent-to-treat analysis, vision was stable or improved in 61.4% of patients treated with Visudyne therapy compared to 45.9% of patients administered placebo. The difference was statistically significant for the broad range of patients who were entered into the trials. Accordingly, patients treated with Visudyne therapy were 34% more likely to retain their vision compared to the placebo group.

Further, among those patients receiving Visudyne therapy, 16% experienced an improvement in vision of one or more lines on a standard eye chart compared to 7% for those patients receiving placebo.

Statistically significant results on the combined data favoring Visudyne therapy were also obtained for all secondary endpoints, including contrast sensitivity and lesion growth. Visudyne therapy was more likely to confine the growth of the lesion as well as maintain contrast sensitivity relative to patients receiving placebo.

Results also showed that Visudyne therapy was well tolerated, with less than 2% of patients withdrawing from the study due to adverse events. The majority of adverse events occurred in similar numbers among the treatment and placebo groups. Those events that occurred more often with Visudyne therapy were: reactions at the injection site that occurred in 9% more treated patients; transient mild to moderate decreased vision that occurred in 2% more treated patients; and self-resolving photosensitivity reactions that occurred within 24 hours post-treatment in approximately 2% of treated patients.

It was also shown in the Phase III studies that, with re-treatment, the effect of Visudyne therapy can be sustained for at least one year. Patients in the study received an average of 3.4 treatments during the 12-month period.

A complete analysis of the 12-month results of the TAP Investigation is currently underway and is expected to be submitted to a peer-reviewed medical journal and presented at the annual Association of Research in Vision and Ophthalmology (ARVO) meeting in Fort Lauderdale, Florida, scheduled for May 9-14, 1999.

Wet AMD is characterized by the formation of abnormal leaky blood vessels that grow across the central part of the retina, called the macula. Although the wet form of AMD represents an estimated 15% of all AMD cases, it accounts for approximately 90% of the severe vision loss associated with the disease. Worldwide, nearly 500,000 new cases of wet AMD occur each year. In North America, up to 200,000 new cases develop annually. These estimates are expected to grow dramatically as the baby boom population ages.

"It is important to note that, while this is a promising potential new treatment because of its ability to confine retina damage, this therapy does not restore vision in eyes that have already been significantly damaged by AMD," added Dr. Bressler.

We are extremely excited about these results as they confirm the potential of Visudyne therapy to satisfy a major unmet need among patients and eye care professionals," said Luzi von Bidder, President of CIBA Vision's worldwide Ophthalmics Business Unit. "We are aggressively completing submissions to appropriate regulatory bodies in the U.S., Canada, and Europe to ensure general availability of the therapy in early 2000."

The TAP study findings expand on the observations made in prior Phase I/II studies involving 142 patients, which showed that the selective properties of Visudyne therapy cause the cessation of leakage by abnormal blood vessels without harming vision.

"These positive results give me a great deal of personal satisfaction, knowing that a drug discovered by QLT has the potential to benefit so many people diagnosed with this devastating condition," said Dr. Julia Levy, President and Chief Executive Officer of QLT. "This accomplishment certainly moves QLT closer to achieving our goal of becoming one of the world's leading biopharmaceutical companies."

In view of the prevalence of AMD and the absence of a satisfactory existing treatment for most cases, high patient expectations and strong interest among eye care professionals in this potential new therapy is anticipated. To help meet the requests for information by patients and eye care professionals, QLT and CIBA Vision have established a web site and country specific patient/practitioner information lines where up-to-date information can be obtained. In North America, the number is 1-800-821-2450 (see attached list for other countries) and the web site address is www.visudyne.com.

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