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| |  Visudyne Reduces Risk Of Vision Loss Associated With Wet AMD ATLANTA, GA, and VANCOUVER, B.C. -- October 15, 1999 -- Extensive positive results show Visudyne (verteporfin for injection) is effective in the treatment of the wet form of age-related macular degeneration (AMD), the leading cause of blindness in people over the age of 50 in the western world. These findings from Phase III clinical trials appear in the October issue of the Archives of Ophthalmology, the first time that such evidence has been published in any leading peer-review medical journal. The overall results of the study report that Visudyne therapy reduces the risk of vision loss, compared to placebo, during the first year of the study in patients with the wet form of AMD. The comprehensive analysis reveals that Visudyne therapy shows beneficial effects in the total study population. Additionally, the data shows that a subgroup of patients whose lesions were characterized by a specific, more aggressive, disease pattern experienced a large, clinically relevant benefit. Regulatory applications, based on the data, requesting marketing clearance for Visudyne therapy have recently been submitted to the US Food and Drug Administration (FDA), as well as boards of health in the European Union, Switzerland, Australia, and New Zealand. In the United States, Switzerland, Australia and New Zealand, the application has been granted accelerated review status. Wet AMD typically destroys central vision, which is necessary for reading, driving, and recognizing faces. The condition is characterized by the formation of abnormal blood vessels (choroidal neovascularization or CNV) that grow across the central part of the retina, called the macula. These vessels leak fluid and, eventually cause scar tissue, which destroys central vision in as little as 2 months to 3 years. As the population ages, wet AMD is predicted to increase as a major public health concern, particularly since current treatment options are limited in efficacy and scope.
Positive Results in the Broad, Total Study Population The findings were the results of a 12-month analysis from two 24-month, randomized, double-masked, clinical trials involving 609 patients with a variety of CNV lesion characteristics, known as the TAP (Treatment of AMD with Photodynamic therapy). Investigation showed that vision remained stable or improved (defined as a loss of less than three lines of vision on a standard eye chart) for 61 percent of patients treated with Visudyne therapy compared to 46 percent of patients administered placebo (p<0.001). This result was statistically significant for both the combined and individual studies. Compared to placebo, the beneficial effects of Visudyne therapy with respect to change in visual acuity were observed at the first follow-up period three months after initial treatment and became more pronounced through month 12. The entire change in visual acuity distribution at 12 months differed by an average of 1.3 lines in favor of those patients on Visudyne (p<0.001). "This is a landmark study with results that have the potential to significantly change the way we manage patients developing wet AMD," said Dr. Neil M. Bressler. Dr. Bressler is 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. "Visudyne therapy offers hope for potentially preserving the vision and independence of many thousands of people diagnosed around the world each year with predominantly classic CNV." Although the goal of Visudyne therapy is to reduce the risk of vision loss, 16 percent of patients in the treatment group experienced an improvement in vision of one or more lines on a standard eye chart compared to 7 percent of patients on placebo. This result confirms that the improvement seen in earlier studies with shorter-term follow up was sustainable for at least 12 months. Severe vision loss (defined as a loss of at least 6 lines of vision on a standard eye chart) occurred in 14.7 percent of patients treated with Visudyne therapy as opposed to 23.7 percent of patients on placebo (p<0.001). In order to participate in the trials, patients had to have a best-corrected baseline visual acuity of between 20/40 and 20/200 as well as some evidence of the fluorescein angiographic pattern regarded to be the more aggressive type, termed classic CNV. Positive visual acuity results were complemented by similar outcomes for contrast sensitivity evaluations. In addition, fluorescein angiographic assessments demonstrated that Visudyne significantly reduced the risk of lesion growth, was associated with the cessation of leakage from classic CNV and decreased progression in the development of new areas of classic CNV beyond that observed at study entry. Specifically, at 12 months, Visudyne-treated eyes had a lower mean number of contrast sensitivity letters lost (1.3 vs. 4.5, p<0.001) and were less likely to show progression of classic CNV beyond the original lesion (46 percent vs. 71 percent, p<0.001), have fluorescein leakage from classic CNV (77 percent vs. 88 percent, p=0.002), and have a lesion size larger than 6 disc areas (41 percent vs. 73 percent, p<0.001).
Substantially Enhanced Results in Specific Subgroup No subgroups were identified in which placebo-treated patients fared significantly better than patients receiving Visudyne therapy. However, the visual acuity benefit observed in the overall population was substantially enhanced in 243 patients whose lesions at baseline constituted predominantly classic CNV (> or = 50 percent classic). Vision remained stable or improved in 67 percent of these patients treated with Visudyne therapy versus 39 percent on placebo (p<0.001). At 12 months, 12 percent of these patients on Visudyne therapy had lost greater than six lines of vision whereas 33.3 percent of placebo patients in this subgroup had experienced severe vision loss (p<0.001). "This finding identifies a very clinically relevant and substantial indication for justifying prompt consideration of treatment for AMD patients with subfoveal lesions who present with predominantly classic CNV," said Dr. Bressler.
Visudyne therapy well-tolerated The therapy was well tolerated with few adverse events, and less than 3 percent 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 10 percent more treated patients; transient mild to moderate transient visual disturbances that occurred in 2 percent more treated patients; and self-resolving photosensitivity reactions that usually were mild and occurred within 24 hours post-treatment in less than 3 percent of treated patients. “In addition to the significant reduction in risk of vision loss noted with Visudyne therapy in these trials, we are extremely pleased with the product’s excellent safety profile. This is an important finding, particularly since the drug will be used primarily in a population whose average age probably will be around 75,” said Dr. Bressler. “We certainly are indebted to the hundreds of patients that participated in this trial,” he added, “Their commitment is evident by the fact that over ninety-four percent of the participants given Visudyne or placebo therapy completed their 12-month follow-up exam.”
Protocol Two-thirds of the 609 participants in the trials received Visudyne via intravenous injection over ten minutes while the remaining one-third were administered a placebo in a masked fashion. Fifteen minutes after the start of the infusion, a non-thermal light was shone into the patient’s eye for approximately one and one-half minutes to activate the drug. Once activated, Visudyne selectively affects the abnormal blood vessels, resulting in a greater chance to stop growth of these blood vessels and corresponding vision loss compared to placebo treatment. Re-treatments were administered every three months if leakage was identified on fluorescein angiography. At the 12-month time period, only 64 percent of the Visudyne-treated patients required re-treatment.
Study Conclusions "Based on these results, we recommend the use of Visudyne therapy in the management of AMD patients with subfoveal CNV lesions that are predominantly classic CNV, once the drug is approved by regulatory agencies for commercial use," said the study authors. "The fact that these trials were rigorous and well-controlled makes these results even more compelling," added Dr. Bressler.
About Visudyne Therapy and AMD Visudyne therapy is being co-developed for various ocular conditions by CIBA Vision Corporation, the eye care unit of Novartis AG, and QLT PhotoTherapeutics Inc. (Nasdaq: QLTI; Toronto). Upon commercialization, CIBA Vision will market the product worldwide while QLT will be responsible for manufacturing Visudyne. Pending regulatory approval, the companies hope to make Visudyne therapy commercially available by early 2000. Visudyne therapy involves the use of a specifically designed laser that produces the low level, non-thermal 689 nm light required to activate the drug. These lasers have been developed by two of the world’s leading laser companies, Coherent Inc. (Nasdaq: COHR), based in California, and The Carl Zeiss Group, based in Germany. Additional Phase III trials are being conducted to determine the effectiveness of Visudyne therapy in patients with an earlier stage of AMD who were originally excluded from the TAP Investigation, as well as patients with a similar but distinct condition of abnormal blood vessels associated with progressive near-sightedness known as pathologic myopia. The wet form of the condition represents an estimated 15 percent of all AMD cases, but accounts for approximately 90 percent of the severe vision loss associated with the disease. Worldwide, nearly 500,000 new cases of wet AMD develop each year, 200,000 of which occur in North America. Visudyne therapy is protected by a series of U.S. and foreign issued patents which cover the composition of matter, formulations and manufacturing, and the method of use in treating AMD and other conditions.
Related Links: CIBA Vision Corporation, Novartis AG and QLT PhotoTherapeutics Inc.
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