Pegaptanib shows evidence of functional, anatomic benefits in eyes with non-ischemic central retinal vein occlusion

April 15, 2008

Results of a phase II study evaluating pegaptanib sodium (Macugen, OSI Eyetech/Pfizer) intravitreal injection in eyes with macular edema (ME) secondary to nonischemic central retinal vein occlusion suggest a potential role for vascular endothelial growth factor blockade to reduce ME and improve visual acuity.

Key Points

Indian Wells, CA-Intravitreal injection of pegaptanib sodium (Macugen, OSI Eyetech/Pfizer) appears to have positive effects in eyes with non-ischemic central retinal vein occlusion (CRVO), according to results from the Macugen in CRVO Study.

Speaking on behalf of his co-investigators at the annual meeting of the American Society of Retina Specialists, Jack Wells, MD, presented the findings through 1-year of follow-up that showed pegaptanib treatment improved vision in parallel with reducing macular edema (ME).

"Vascular endothelial growth factor [VEGF] is believed to play a central role in the complications associated with CRVO, but, to our knowledge, this is the first prospective, randomized clinical trial of anti-VEGF therapy for treatment of ME secondary to CRVO," said Dr. Wells, a vitreoretinal specialist in private practice in Columbia, SC. "We believe the favorable anatomic and functional results observed suggest selective VEGF blockade is a promising therapeutic approach for retinal venous occlusive disease."

Intravitreal injections were given at baseline (week 0) and then every 6 weeks through week 24, for a total of five injections. Primary and secondary efficacy analyses, including ETDRS VA outcomes and changes in optical coherence tomography (OCT)-measured central retinal thickness, were based on data collected at the week 30 and week 52 visits.

Patients were eligible for participation if CRVO had occurred within the previous 6 months and best-corrected VA in the study eye was between 65 and 20 ETDRS letters (approximately 20/50 to 20/400). Presence of ME identified by OCT was required, and central retinal thickness had to be at least 250 µm at the screening and first treatment visit. The major exclusion criteria prohibited enrollment of patients with brisk afferent pupillary defect or ocular neovascularization.

The proportion of eyes gaining 15 or more letters from baseline VA to week 30 was analyzed as the primary efficacy endpoint. The results showed a trend in favor of the pegaptanib arms, with that outcome being achieved in 36% of patients treated with the 0.3-mg dose and in 39% of patients treated with the 1.0-mg dose, compared with 28% of sham-treated patients. The difference was not statistically significant between either treatment group and sham, however.

"The improvement noted in the sham group points out that the natural history of CRVO can be quite favorable and, therefore, emphasizes the need for randomized trials to investigate the efficacy of treatments for this disease," said Dr. Wells.

VA changes

An analysis of change in VA from baseline showed that the benefit of pegaptanib treatment occurred early and was sustained, whereas patients in the sham-treated control group had a loss of vision by week 6 that worsened through week 18 and persisted throughout the follow-up. At week 30, patients treated with pegaptanib 0.3 mg had a mean 7.1 letter gain from baseline VA, and the 1.0-mg group benefited with a mean 9.9-letter gain. The difference in change from baseline vision comparing the pegaptanib 1.0 mg group and the sham group was a mean of 13.1 letters and was statistically significant. The mean difference in change from VA from baseline between the pegaptanib 0.3 mg group and the controls was 10.3 letters, but it did not achieve statistical significance.

The week 30 VA data also were analyzed to compare the percentage of patients who lost 15 or more letters from baseline and the percentage with VA of 35 letters or better (~20/200). For these endpoints, statistically significant differences favored both pegaptanib groups compared with the control arm.

In the sham group, 31% of eyes lost 15 or more letters of vision compared with 9% of eyes in the pegaptanib 0.3 mg group and 6% of eyes treated with pegaptanib 1.0 mg. About 90% of eyes in both pegaptanib groups retained vision of 35 letters or better, compared with only 63% of eyes in the sham group.