New Drug Maintains Visual Acuity in CRVO at 1 Year

October 28, 2011 (Orlando, Florida) — The 1-year results of the COPERNICUS trial show that patients with macular edema secondary to central retinal vein occlusion (CRVO) who received injections of VEGF Trap-Eye (Regeneron Pharmaceuticals) on an as-needed basis after receiving the drug once a month for the first 6 months of the study are able to maintain their initially improved visual acuity, researchers reported here at the American Academy of Ophthalmology 2011 Annual Meeting.

Dr. Julia Haller

"When we went to an as-needed protocol instead of every month, patients held on to their visual gains. The median vision went from 17.3 letters to 16.2 letters, and the 55% 3-line gainer mark was hit yet again, so they held on," lead author Julia Haller, MD, ophthalmologist-in-chief at the Wills Eye Institute and professor and chair of the Department of Ophthalmology at Thomas Jefferson University in Philadelphia, Pennsylvania, told Medscape Medical News.

Patients who received sham treatment, however, actually lost visual acuity; this improved once they crossed over to active treatment in the second 6 months of the trial, but they never caught up to the patients who received VEGF Trap-Eye initially, she added.

The 6-month data from COPERNICUS were previously reported by Medscape Medical News.

In the trial, patients were randomized in a 3:2 ratio, with 114 patients receiving VEGF Trap-Eye 2 mg and 73 patients receiving sham injections every 4 weeks for 6 months.

At the end of the initial 6 months, all patients randomized to VEGF Trap-Eye continued with it on an as-needed basis and patients originally randomized to sham injections crossed over to as-needed VEGF Trap-Eye for the second 6 months of the trial.

The mean age of the patients in the sham group was 68 years and in the VEGF Trap-Eye group was 66 years.

At week 24, 56.1% of the VEGF Trap-Eye group gained 15 or more letters, compared with 12.3% of the sham group.

The 52-week data presented by Dr. Haller showed that in the VEGF Trap-Eye group, 55.3% retained a gain of 15 or more letters; in the sham group, that rose to 30.1%. Although patients in the sham group did gain after crossing over to active drug treatment, they did not attain the same good results as those who started with active drug at baseline.

Those in the sham group also used more as-needed injections than those in the VEGF Trap-Eye group (4 vs 3 injections).

The mean change in visual acuity in the VEGF Trap-Eye group was 17.3 at 6 months; at 12 months, it was 16.2. In the sham group, it was –4.0 at 6 months and 3.8 at 12 months (P < .001).

Both the sham and VEGF Trap-Eye groups had a reduction in retinal thickness at 12 months, although the reduction was greater in patients who received the active drug for the entire 12 months. In the sham group, retinal thickness was reduced by 381.8 microns; in the VEGF Trap-Eye group, retinal thickness was reduced by 413.0 microns (P < .001).

Better Retinal Perfusion but More Ocular Neovascularization

The study also found that patients who were treated had better retinal perfusion. At baseline, retinal perfusion was equal in the sham (69%) and VEGF Trap-Eye (68%) groups, but by week 24, the proportion of patients with perfused retina was 57% in the sham group and 86% in the VEGF Trap-Eye group. By week 52, that proportion had evened out again, with 84% of the sham group and 86% of the VEGF Trap-Eye group showing retinal perfusion.

In addition, there was no ocular revascularization in the VEGF Trap-Eye group, either at week 24 or at week 52. In comparison, 6.8% of the sham group patients had ocular neovascularization at week 24 and at week 52 (P = .006).

VEGF Trap-Eye was well tolerated; the most common adverse events were associated with intravitreal injections, Dr. Haller noted.

"This is good information. VEGF Trap-Eye works and appears to have some durability of effect when given on an as-needed basis," she said. She acknowledged that this trial does not comparing it "head to head with any of the other available therapies, but there were no significant safety signals, so it looks to be safe."

Dr. Mark Johnson

Medscape Medical News invited Mark W. Johnson, MD, professor of ophthalmology at the University of Michigan Kellogg Eye Center, Ann Arbor, Michigan, who moderated the oral paper session, to give his views on the 1-year results from COPERNICUS.

"The COPERNICUS trial demonstrated impressive visual gains at 6 months in eyes with CRVO treated monthly with 2 mg VEGF Trap-Eye, compared with eyes receiving sham treatment," Dr. Johnson said.

He noted that there was a concomitant and substantial decrease in macular edema in treated eyes, "confirming the important role of VEGF in the pathogenesis of cystoid macular edema complicating CRVO."

Dr. Johnson added that he thinks it is interesting that monthly injections of VEGF Trap-Eye appear to prevent progression of retinal capillary nonperfusion as well as the development of anterior segment neovascularization.

He pointed out, however, that "the study provides no information about less-than-monthly dosing or the durability of treatment effect if injections are discontinued. It also provides no comparison to treatment with intravitreal corticosteroid agents."

Dr. Haller reports financial relationships with Allergan, Genentech, OptiMedica, and ThromboGenics. Dr. Johnson reports financial relationships with Ophthotech, Oraya, Regeneron, and ThromboGenics.

American Academy of Ophthalmology (AAO) 2011 Annual Meeting: Abstract PA033. Presented October 24, 2011.