Lara C. Pullen, PhD

November 13, 2012

CHICAGO — New data indicate that patients receiving intravitreal aflibercept (IAI) continue to have considerable and sustained improvements in visual acuity after 1 year of treatment. These results can be maintained even with less frequent dosing.

Jean-Francois Korobelnik, MD, of the Hospital Pelligrin in Bordeaux, France, presented data from the phase 3 GALILEO study, and David Brown, MD, of Retina Consultants Houston in Texas, presented the results of the phase 3 COPERNICUS study.

These sister studies were designed to evaluate the efficacy and safety of IAI vs sham treatment. The international clinical trial perspective was presented and discussed here at the American Academy of Ophthalmology (AAO) 2012 Annual Meeting. The GALILEO trial took place in Europe and Asia, and the COPERNICUS trial was conducted in North America. Both trials were randomized, multicenter, double-masked trials in treatment-naive patients with macular edema secondary to central retinal vein occlusion.

The GALILEO trial included 71 patients in the sham group (73.2% completed the study) and 106 patients in the treatment group (84.9% completed the study). The moderator of the session noted that due to the proven efficacy of IAI, the GALILEO and COPERNICUS trials were likely to be the last of such trials approved with a sham group.

Patients who received treatment with fixed monthly IAI over 24 weeks experienced rapid and sustained gains in visual acuity. At 52 weeks, 60.2% of IAI patients gained 15 or more letters compared with 12.3% of sham group patients (P < .001). Gains in visual acuity were largely maintained with monthly monitoring and less frequent PRN dosing.

Corneal refractive therapy and percentage of patients without retinal fluid deteriorated when patients were switched from fixed dosing to PRN dosing with monthly monitoring and again to PRN dosing with infrequent monitoring. There were no Anti-Platelet Trialists' Collaboration (APTC) events reported during the study.

Sophie J. Bakri, MD, of the Mayo Clinic in Rochester, Minnesota, was on the panel of the vitreous retina session and noted, "That was a very nice paper.... Certainly this reflects a regimen with less frequent injections than the previous trials."

Carl D. Regillo, MD, of Thomas Jefferson University School of Medicine in Philadelphia, Pennsylvania, was also on the panel and added, "What worries me is that the style of treatment is not likely to be a suitable optimal form of therapy for some patients." He elaborated by asking how ophthalmologists can best treat patients who need ongoing therapy. Although there are good, long-term data for PRN therapy, this type of therapy may not be realistic for the general population.

Dr. Brown noted that the GALILEO study was a 52-week study, whereas the COPERNICUS study had a 6-month crossover design. In all other respects, the 2 study designs were the same.

In the COPERNICUS study, 88.7% of patients in the experimental group completed the study; 67.6% of patients in the sham treatment group completed the study. At week 24, 56.1% of patients in the IAI group gained 15 or more letters compared with 12.3% of patients in the sham group (P < .001).

Dr. Brown noted that patients who received IAI after the crossover had measurable "damage from the 6 months of edema due to delay in therapy." The visual and anatomic improvements observed at the end of the fixed dosing period were diminished after changing to PRN dosing.

Dr. Brown explained that "crossing over at 24 weeks is beneficial, but nothing like starting early."

Dr. Korobelnik, Dr. Bakri, and Dr. Regillo have disclosed no relevant financial relationships. Dr. Brown is a consultant and receives lecture fees from Regeneron.

American Academy of Ophthalmology (AAO) 2012 Annual Meeting: Abstracts PA048 and PA049. Presented November 12, 2012.