Pegaptanib sodium therapy points to interesting avenues for future research

October 14, 2005

Anti-vascular endothelial growth factor (VEGF) therapy has been validated as the foundation treatment for age-related macular degeneration (AMD), evidence-based medicine should drive practice patterns, combination therapies should improve results, early treatment of early disease is a better approach, and anti-VEGF therapies will have a wider role to play than solely in AMD, stated Lawrence Singerman, MD, Friday during the retina subspecialty day at the American Academy of Ophthalmology.

Chicago-Anti-vascular endothelial growth factor (VEGF) therapy has been validated as the foundation treatment for age-related macular degeneration (AMD), evidence-based medicine should drive practice patterns, combination therapies should improve results, early treatment of early disease is a better approach, and anti-VEGF therapies will have a wider role to play than solely in AMD, stated Lawrence Singerman, MD, Friday during the retina subspecialty day at the American Academy of Ophthalmology.

In the VEGF Inhibition Study in Ocular Neovascularization trials, pegaptanib sodium (Macugen, OSI Pharmaceuticals/Eyetech Pharmaceuticals) was shown to be safe and effective. Tightening the protocol reduced the incidence of endophthalmitis from 0.18% to 0.04%.

“Macugen was shown to be a successful foundation monotherapy in that 70% of the patients who received Macugen compared with 55% of the patients who received sham therapy did not have a 15-letter loss of visual acuity,” Dr. Singerman said. He is president, Retina Associates of Cleveland, and clinical professor of ophthalmology, Case Western Reserve University School of Medicine.

Dr. Singerman emphasized that if ophthalmologists believe in the results of randomized clinical trials, they should respect the regimens used in the clinical trials and not be easily dissuaded by imaging studies that may not reflect the desired results.

He showed the examples of patients who had initial worsening of vision after pegaptanib sodium therapy who later had gains in vision because of adherence to the regimen suggested in the clinical trial.

“Adherence to the full treatment regimen protects against severe vision loss during the first year of the Macugen vision trial. If the patients received all nine injections, there was an 8% chance of severe vision loss at 54 weeks of treatment compared with a 15% of chance of severe vision loss if they received fewer than the nine injections. There was an 89% chance of severe vision loss if the regimen was compromised,” he said.

Combination therapy also looks promising. In a group of patients who received photodynamic therapy and pegaptanib sodium, 60% gained three or more lines of vision compared with 25% of patients who received pegaptanib sodium alone.

“This may be the way to go,” Dr. Singerman said. Various combination trials are ongoing.

“It is logical that attacking the disease process at multiple steps in its pathway, should improve the results if the right drugs are used,” he said. “These drugs may be those that work best together and not necessarily the most effective monotherapies.”

Anti-VEGF therapy may also prove to be effective in diabetic macular edema, central retinal vein occlusion, and iris neovascularization.