Pegaptanib may have expanded applications beyond AMD

April 15, 2006

Cleveland?Anti-vascular endothelial growth factor (VEGF) therapy has been validated as the foundation treatment for age-related macular degeneration (AMD), stated Lawrence J. Singerman, MD, who provided an update on pegaptanib sodium (Macugen, OSI Pharmaceuticals/Eyetech Pharmaceuticals).

"Almost 50,000 patients have been treated with pegaptanib sodium and it has been shown to be safe. The incidence of endophthalmitis was an issue early in the study of the drug. Tightening the protocol and educating the investigators reduced the incidence of endophthalmitis significantly from 0.18% to 0.04%," he said.

"Pegaptanib sodium was shown to be a successful foundation monotherapy, in that 70% of the patients who received pegaptanib sodium 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; clinical professor of ophthalmology, Case Western Reserve University School of Medicine, Cleveland; and voluntary professor of clinical ophthalmology, Bascom Palmer Eye Institute, Miami.

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

For example, a patient had a three-line loss of vision at week 30 after the start of pegaptanib sodium therapy, despite which the physician continued with treatment. The patient had a two-line gain of vision at week 54 followed by a four-line gain at week 102, which resulted in a final visual acuity of 20/20.

"Adherence to the full treatment regimen protected against severe vision loss during the first year of the pegaptanib sodium 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 small group of patients who received photodynamic therapy (PDT) and pegaptanib sodium in a phase IB study, 60% gained three or more lines of vision compared with 25% of patients who received pegaptanib sodium alone.

"Combination therapy may be the way to go," Dr. Singerman said. Various trials of combination therapies are ongoing. One such study being conducted by Eyetech is of pegaptanib sodium plus sham PDT compared with pegaptanib sodium plus PDT. A second study is comparing PDT plus two different doses of intravitreal triamcinolone acetonide with PDT plus pegaptanib sodium.

Benefits of combination therapy

"It is logical that attacking the disease process at multiple steps in its pathway should improve the results if the right drugs are being used," he said. "These drugs may be those that work best together and not necessarily the most effective monotherapies. Combination therapies will be studied extensively and we hope ranibizumab (Lucentis, Genentech), anecortave acetate (Retaane, Alcon Laboratories), and other drugs will be approved soon so that we can study the enhanced benefit that they might offer to our patients in various combinations."

A recent report in the journal Retina [The VEGF Inhibition Study in Ocular Neovascularization (V.I.S.I.O.N.) Clinical Trial Group. Enhanced efficacy associated with early treatment of neovascular age-related macular degeneration with pegaptanib sodium: An exploratory analysis. 2005;25:815-827] indicated that early treatment of neovascular AMD with pegaptanib sodium enhances the effects of treatment. The results showed, according to Dr. Singerman, that 20% of patients gained three or more lines of vision compared with 0% of patients who were not treated early. In a patient with a 2-week history of disease and a baseline visual acuity of 20/400, the patient achieved 20/25 vision 18 weeks after therapy began.