Ranibizumab trials provide hope for visual improvement

April 15, 2006

Boston?The 12-month results of two randomized clinical trials of ranibizumab (Lucentis, Genentech) indicate that the drug shows encouraging signs of activity against vascular endothelial growth factor (VEGF) in age-related macular degeneration (AMD).

Jeffrey S. Heier, MD, reported the results for the Lucentis Study Group.

FOCUS trial

Dr. Heier explained that because of the investigators' concern about the development of increased inflammation when PDT and ranibizumab were administered within a short time period of each other, the protocol was amended. If additional PDT was needed, then the injection of ranibizumab scheduled for that month was not administered.

"The 12-month results indicated that more than 90% of the patients who received combination therapy reached the primary study endpoint of loss of fewer than 15 letters of visual acuity compared with 68% of patients who received PDT alone," said Dr. Heier, a vitreoretinal specialist at Ophthalmic Consultants of Boston. He is also an assistant professor of ophthalmology, Tufts School of Medicine, and clinical instructor in ophthalmology, Harvard Medical School, both in Boston.

Importantly, 24% of the patients who received combination therapy had an improvement of three or more lines of vision versus 5% of those who received PDT alone, Dr. Heier emphasized.

The secondary endpoint was change of vision. The patients who received PDT alone had the expected loss of vision (losing an average of eight ETDRS letters at 12 months), compared with an increase of vision of almost five letters in the patients who received the combination therapy. This resulted in a difference of 13 letters in the two treatment groups. The investigators also observed a dramatic decline in the need for additional PDT treatments in the group that received combination therapy.

"This was observed at the first evaluation point and became even more dramatic as the study progressed," Dr. Heier stated.

Serious adverse events included two cases of endophthalmitis, three cases of inflammation that were treated as presumed endophthalmitis (considered inflammatory by the investigator, but still treated with intraocular antibiotics), and nine cases of severe uveitis. Despite this, the patients with uveitis had a three-letter gain of vision. After the protocol was changed, no other cases of severe uveitis developed. Systemically, there was a slight trend toward increased hypertension in the group that received combination therapy, although most cases were mild and none considered severe.

The MARINA trial

The MARINA Study (Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD) is a phase III pivotal trial of the treatment of subfoveal minimally classic/occult choroidal neovascularization secondary to AMD. Patients received either sham injections or ranibizumab (0.3 or 0.5 mg) injections for 24 treatments over 2 years . The protocol was one injection per month.

The 12-month results indicated that "there was a dramatic difference between the patients who received ranibizumab, 95% of whom lost fewer than 15 letters of vision compared with about 62% of the control patients," Dr. Heier reported.

Evaluation of the secondary endpoint, loss of vision, showed that the patients treated with sham injections lost an average of 10 letters compared with an average seven-letter gain in the treatment groups. This translated into a difference of 17 letters between the sham-treated and ranibizumab-treated patients.

There were very few cases of uveitis and endophthalmitis in this study, which used a different formulation from that used in the FOCUS study and the other phase I/II trials. There were also fewer systemic events compared with the FOCUS study.