Pegaptanib effective for retinal vascular disease

August 1, 2007

Selective VEGF inhibition appeared to produce improvements in vision and macular edema in patients with central retinal vein occlusion in a recent study. In this multicenter, randomized trial, patients with macular edema secondary to CRVO received five intravitreal injections of pegaptanib sodium over a 24-week period.

Key Points

Fort Lauderdale, FL-A recent study seems to show positive effects of pegaptanib sodium (Macugen, OSI/Eyetech) injections on vision and macular edema secondary to central retinal vein occlusion (CRVO).

"No previous randomized trial has demonstrated a treatment benefit for macular edema and vision in CRVO, so this approach seems to be a promising one for the treatment of retinal vascular disease," John A. Wells III, MD, said during a presentation at the annual meeting of the Association for Research in Vision and Ophthalmology.

Selective vascular endothelial growth factor (VEGF) blockade was the key principle in this trial. In clinical practice, inhibition of angiogenesis and vascular hyperpermeability are the primary goals of anti-VEGF therapy, but several other effects of VEGF might be important to preserve in a disease such as CRVO, such as neuroprotection and modulation of blood flow, Dr. Wells said. CRVO is characterized by damage to the retinal vasculature, vascular occlusion, ischemia, and damage to the neurosensory retina.

He said part of the rationale for conducting this study was that another study found a doubling of the cardiovascular mortality rate in patients aged fewer than 70 years who experience a retinal vein occlusion, and recent concern about increased stroke risk in patients using pan-VEGF blockers for ocular disease.

Dr. Wells explored the safety and efficacy of pegaptanib when given by intravitreous injection every 6 weeks in patients with recent vision loss due to macular edema secondary to CRVO. In this prospective, multicenter, controlled, double-masked, dose-finding study, patients with CRVO were randomly assigned in a 1:1:1 ratio to pegaptanib, 1.0 mg or 0.3 mg, or sham.

Panretinal photocoagulation was permitted for neovascularization per Central Vein Occlusion Study guidelines. Patients received a total of five injections over 24 weeks; results were analyzed at weeks 30 and 54.

Key ocular inclusion criteria were that CRVO occurred within 6 months prior to baseline and that best corrected visual acuity (VA) in the study eye was between 65 and 20 ETDRS letters inclusive, or approximately 20/50 to 20/400. Macular edema was determined by optical coherence tomography, and central retinal thickness had to be ≥250 µm at baseline and day 0. Subjects with brisk afferent pupillary defect or ocular neovascularization at baseline were excluded.

Enrollment included 98 subjects at 36 centers internationally. At baseline, the three groups were comparable in age, gender, and blood pressure. Baseline mean VA was approximately 48 letters (about 20/100) in all three study arms, and mean center point retinal thickness at baseline was also comparable across study arms, ranging from 642 to 687 µm.

"The mean change in VA showed an early and sustained effect of [pegaptanib] treatment compared with control," Dr. Wells said. "By week 30 with the 1.0-mg dose, there was an almost 10-letter gain of vision versus a 3-line loss in the sham group for a 13-letter difference, and this was significantly different (p < 0.05). However, while the 0.3-mg group had a 10-letter difference between controls, it was not statistically significant."

Although a trend favored the pegaptanib arms, the results failed to meet the primary pre-established endpoint of the trial, which was the proportion of patients achieving a gain of at least 3 lines at week 30.

"It's important to know that in the control group, almost 30% of patients had a relatively favorable outcome, and this just emphasizes that the natural history of CRVO can be relatively good in a significant minority of patients, and it also emphasizes that if you're looking at treatment of CRVO, you need to have randomized controlled trials," Dr. Wells said.