Brand Name Drug: Visudyne
Active Ingredient Drug: verteporfin for injection
Indication: Treatment of wet form of age-related macular degeneration
Company Name: CIBA Vision, the eye care unit of Novartis Pharmaceuticals Corporation
Availability: Approvable letter issued by FDA on February 11, 2000
Age-related macular degeneration (AMD) is the leading cause of blindness among people over the age of 50 in the western world. It is characterized by two forms: the “dry” form, as well as the more severe “wet” form. While the wet form of AMD – which afflicts about 500,000 people each year – is responsible for only about 15% of all AMD cases, it accounts for some 90% of the severe vision loss associated with AMD. Wet AMD typically destroys central vision in as little as two months to three years; central vision is necessary for reading, driving, and recognizing faces.
The most common form of age-related macular degeneration treatment has been laser photocoagulation, which helps prevent the progression of choroidal neovascularization (CNV) in the 10-20% of AMD patients who have small, discrete lesions. However, the thermal lasers used in this technique also destroy healthy retinal tissue, resulting in an immediate loss of visual acuity after treatment.
In February the FDA issued an approvable letter for a promising new treatment for patients with the wet form of AMD. Called Visudyne, the therapy – which can be performed in a doctor’s office – involves intravenous injection of the drug verteporfin into the patient’s arm, followed 15 minutes later by a 90-second treatment of the eye with a low-level, nonthermal 689 nm laser, which activates the drug. Such photodynamic therapy (PDT) destroys abnormal choroidal blood vessels while leaving normal vessels functional. Visudyne is manufactured by CIBA Vision, the eye care unit of Novartis Pharmaceuticals Corporation. It was approved for marketing in Switzerland last December and is also under regulatory review in other countries.
How It Works
It is believed that once in the bloodstream, Visudyne therapy complexes with low-density lipoprotein (LDL). The newly formed LDL-Visudyne complex is taken up by the endothelial cells of the abnormal choroidal blood vessels, which have high levels of LDL-receptors. Visudyne therapy is then activated with red light after the start of the infusion. Because the laser does not generate heat, the overlying retina is not harmed by the technique.
Oxygen free radicals released during the photochemical reaction lead to platelet activation and occlusion of the abnormal blood vessels, leading to vessel destruction. Retinal vessels are unaffected by the treatment. PDT with Visudyne therapy cannot restore damaged photoreceptors or damaged retinal cells, but it may maintain vision by confining the spread of choroidal neovascularization. A short-term improvement in vision may be observed, probably due to the reduction of subretinal fluid.
Visudyne: Clinical Study Results
A one-year 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 3 lines of vision on a standard eye chart) for 61% of patients treated with Visudyne therapy compared to 46% of patients administered placebo – a significant difference. Patients in these studies had a late form of wet AMD.
Compared to placebo, the beneficial effects of Visudyne therapy with respect to change in visual acuity were observed 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. Although the goal of Visudyne therapy is to reduce the risk of vision loss, 16% of patients in the treatment group experienced an improvement in vision of one or more lines on a standard eye chart, compared to 7% of patients on placebo. Severe vision loss (defined as a loss of at least 6 lines of vision on a standard eye chart) occurred in 14.7% of patients treated with Visudyne therapy as opposed to 23.7% of patients on placebo.
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 choroidal neovascularization beyond that observed at study entry.
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. Vision remained stable or improved in 67% of these patients treated with Visudyne therapy versus 39% on placebo. At 12 months, 12% of these patients on Visudyne therapy had lost greater than six lines of vision, whereas 33.3% of placebo patients in this subgroup had experienced severe vision loss.
Repeat treatments were administered every three months if leakage was identified on fluorescein angiography. At the 12-month time period, only 64% of the Visudyne-treated patients required repeat treatment.
Additional clinical trials are being conducted to assess the efficacy of Visudyne for patients with an earlier stage of age-related macular degeneration, pathologic myopia, and ocular histoplasmosis.
What the Patient Should Know
Visudyne therapy is generally well tolerated, with few adverse events. In the clinical trials, those events that occurred more often with Visudyne therapy were reactions at the injection site, mild to moderate transient visual disturbances, and self-resolving photosensitivity reactions (usually mild and occurring within 24 hours post-treatment in less than 3% of patients).