New hope may be on the horizon for some people with the “wet” form of macular degeneration (AMD), an eye disease in which abnormal blood vessel growth causes loss of vision. Results of two large international clinical trials have shown positive results using Macugen, an experimental treatment that targets these abnormal blood vessels. The results, described last weekend at the American Academy of Ophthalmology’s annual meeting in Anaheim, Calif., demonstrated the drug’s ability to decrease vision loss in this form of AMD.
The Massachusetts Eye and Ear Infirmary (MEEI) in Boston participated in the clinical trials. In addition, researchers and physicians at MEEI – Tony Adamis (formerly of MEEI), Evangelos Gragoudas, and Joan Miller – were among the first to study the role of vascular endothelial growth factor (VEGF), which causes abnormal blood vessel growth in eye disease. Their experimental studies showed that levels of VEGF protein were increased in eyes that developed abnormal new blood vessels, and that VEGF-blocking drugs were able to prevent the growth of these abnormal blood vessels.
Others, including Harvard’s Lloyd Paul Aiello of the Joslin Diabetes Center and Lois Smith of Children’s Hospital, corroborated the importance of VEGF in neovascular eye disease. These studies formed the basis for the drug development and clinical trials of anti-VEGF therapies, including Macugen, and demonstrate the importance of translational research, in order to transform scientific discoveries into new therapies for patients.
Age-related macular degeneration is the most common cause of severe vision loss in people over 50 and affects approximately 200,000 yearly in the United States alone. In wet AMD, abnormal blood vessels grow under the central retina and cause a progressive loss of central vision, interfering with driving, reading, and other everyday tasks.
Macugen differs from current treatments, which are directed at the results of the disease. Current treatments, which employ a drug and laser, are able to slow vision loss, but have not been widely applicable to all patients. Macugen is the first treatment designed to target the source of the disease. Macugen blocks the pathological form of a chemical called VEGF, which is produced in the eyes of patients with wet AMD.
The Macugen study involved 1,186 patients with wet AMD enrolled into one of four treatment variants: three drug doses and placebo. One-year follow-up demonstrated a benefit to the treatment, with preserved vision (patients lost less than three lines on the eye chart) in 70 percent of eyes receiving Macugen compared to 55 percent in the placebo group, a result that was statistically significant. Macugen was effective at all of the doses tested. A gain of two or more lines of vision was observed in 11 percent of patients receiving Macugen compared to 6 percent receiving the placebo. The drug appeared to be safe, with no increased risk of cardiovascular or other systemic effects. Some patients received a combination of Macugen and photodynamic therapy, but those results were not presented at the meeting. Macugen is administered by an injection into the eye, given every six weeks in an ophthalmologist’s office. Macugen may be available by late 2004 or early 2005, pending review by the FDA.
“Although the treatment effect was modest, it was demonstrated to benefit people with three types of wet AMD. For two of these types, we currently do not have an FDA-approved treatment,” said John Loewenstein, a retinal specialist at the Massachusetts Eye and Ear Infirmary and investigator for some of the trials. “The drug will allow us to treat more patients who have this devastating eye disease. There is a small risk of significant complications from the injections that must be weighed against the treatment benefit. Overall, I think this is a significant addition to our treatment for macular degeneration.”