Interim results of a study of pegaptanib sodium as maintenance therapy for age-related macular degeneration show that patients previously treated successfully with other agents maintain visual and anatomic stability.
Dr. Friberg, professor of ophthalmology, University of Pittsburgh, and director of the retina service, University of Pittsburgh Medical Center Eye Center, presented the interim analysis on the first 83 subjects with 24-week follow-up on behalf of the Evaluation of Efficacy and Safety in Maintaining Visual Acuity with Sequential Treatment of Neovascular AMD (LEVEL) Study Group.
LEVEL is a prospective, multicenter, uncontrolled, open-label study enrolling subjects with neovascular (wet) AMD who were previously treated and experienced improvement in their disease. During the study, they receive maintenance injections of pegaptanib every 6 weeks for 48 weeks. Ancillary ("booster") treatments with any of the agents can be administered at the investigator's discretion using guidelines that define deteriorating AMD, but the pegaptanib injections continue as scheduled. The 54-week trial is enrolling 1,000 patients at 100 sites around the country.
Prior to induction, the mean observed ETDRS acuity was 51.4 letters (about 20/100); by the end of the induction period of 16 weeks, the mean visual acuity (VA) was 64.6 letters (about 20/50). At week 24 of the maintenance phase, the mean VA had declined only slightly, to 64.0 letters, or a 96% maintenance rate. Analysis of the first 162 subjects with 18-week follow-up showed that mean VA was 50.8 letters (20/100) pre-induction, 65.1 letters (20/50) after the induction period, and 63.6 letters (20/50) at the end of that reporting period.
Because the patients were selected for the LEVEL study based on success during induction, the improvement of 13 to 15 letters was perhaps not surprising, but this substantial gain also left them vulnerable to a significant loss of VA during the maintenance phase, Dr. Friberg said.
"Once you substantially improve vision, the patient may be more likely to suffer a sizable setback over time. What was intriguing about the interim results was that we didn't find very much in the way of visual loss after induction," he continued.
In addition, 59% of patients had not received booster treatment. Among those who did, 76% required only one booster, typically with the same agent used during the induction period.
The mean center point thickness was 193 μm at the beginning of the maintenance period and 213 μm at 24 weeks.
At 24 weeks, no evidence was found of an increased risk of systemic hypertension, nonocular hemorrhages, cardiovascular events, or thrombolic events. Also, no evidence of ocular adverse events such as endophthalmitis, retinal detachment, or traumatic cataract was seen.
The purpose of the study was to determine whether treatment could be switched to maintenance therapy with pegaptanib, a selective anti-vascular endothelial growth factor (VEGF) inhibitor, after successful treatment with one of the nonselective agents, such as bevacizumab (Avastin, Genentech) or ranibizumab (Lucentis, Genentech), with multiple agents, or with other forms of therapy. Because pegaptanib has been available longer than other anti-VEGF agents and its safety is arguably better understood, clinicians may be more comfortable using it for long-term maintenance therapy, Dr. Friberg said. This use could be particularly important for patients at high risk of vascular problems such as stroke or myocardial infarction, he added.