AAO/SOE 2008: Ranibizumab Shows Efficacy in Phase 2 Trials of Diabetic Macular Edema

Emma Hitt, PhD

November 10, 2008

November 10, 2008 (Atlanta, Georgia) — Results of 2 phase 2 trials suggest a benefit for ranibizumab (Lucentis, Genentech) in the treatment of diabetic macular edema (DME).

The findings were presented in an oral session here at the 2008 Joint Meeting of the American Academy of Ophthalmology and the European Society of Ophthalmology.

Peter A. Campochiaro, MD, professor of ophthalmology at the Wilmer Eye Institute at Johns Hopkins University, in Baltimore, Maryland, presented 6-month findings from the READ 2 study, which is comparing, in subjects with DME, the effects of intravitreal ranibizumab 0.5 mg with focal laser treatment and a combination of ranibizumab plus focal laser treatment.

Patients were included if they had foveal thickness of at least 250 µm on ocular coherence tomography. Previous treatment was allowed if it had been given at least 3 months prior to study entry (at least 2 months with antiangiogenic agents). Of the 126 patients, 115 completed the study visit at month 6. The results from this population were presented at the meeting.

Improvement in visual acuity of at least 3 lines was observed in 9 patients in the ranibizumab group, compared with 5 in the combination group and 0 in the laser-only group. Visual acuity improved by a mean of 8 letters in the ranibizumab group and 3.8 letters in the combination group; there was a 1-letter loss in the laser-only group. No drug or laser-related adverse events were reported.

"These results substantiate the findings of the READ 1 trial," Dr. Campochiaro told Medscape Ophthalmology. "The RISE and RIDE phase 3 trials will provide more definitive data regarding the effects of ranibizumab in DME," he added. He also noted that future trials will use a more aggressive treatment protocol than the one used in this study, which could further improve efficacy.

In another trial of ranibizumab in DME presented during the same session, Pascale Massin, MD, from the Department of Ophthalmology at the Lariboisière Hospital, in Paris, France, reported 12-month data from the RESOLVE phase 2 trial, which evaluated the safety and efficacy of 2 concentrations of intravitreal ranibizumab in DME.

Dr. Massin noted that retinal vascular endothelial growth factor (VEGF) levels might be "considerably higher" in the retina and vitreous of patients with DME than in patients with neovascular age-related macular degeneration; therefore, DME patients could benefit from a higher dose of ranibizumab, a VEGF inhibitor.

The trial included 151 patients with central macular thickness of 300 µm or more and a best corrected visual acuity (BCVA) letter score of between 39 and 73. Patients had type 1 or type 2 diabetes mellitus and DME with center involvement in at least 1 eye (focal or diffuse).

Subjects were randomized to receive 3 monthly injections with either 0.3 or 0.5 mg ranibizumab or placebo (sham group). Treatment was then administered on an as-needed basis, depending on response to initial treatment. If edema resolution was incomplete, then the dose of ranibizumab was doubled after 1 month. Photocoagulation after 3 injections was given if needed.

Ranibizumab was superior to placebo with respect to changes in BCVA letter score and central retinal thickness. The safety profile of ranibizumab was comparable to that observed in patients with age-related macular degeneration, Dr. Massin said.

When the pooled data from the doubled-dose ranibizumab group (n = 77) were compared with the sham group (n = 32), the difference in mean average change in BCVA was 6.7 for the pooled group (P = .0002). Likewise, the reduction in central retinal thickness was higher in the pooled-dose group than in the sham group.

"These results demonstrate the efficacy of ranibizumab in decreasing retinalthickness and improving visual acuity in DME, and also help confirm the preliminary READ 1 and 2 results," Dr. Massin told Medscape Ophthalmology.

Jennifer Lim, MD, who moderated the session and serves on the READ 2 Executive Committee, told Medscape Ophthalmology that the presentation of the RESOLVE trial "was fascinating because it is known that the VEGF levels in active diabetic retinopathy are higher [than in AMD] and it makes sense that the dose of ranibizumab needed may be correspondingly higher. This use of a higher dose is breaking new ground. The discussion panelists agreed with the rationale and named this presentation best in the session."

The READ 2 study is funded by the Juvenile Diabetes Research Foundation, and the study drug was provided by Genentech. The RESOLVE trial is supported by Novartis. Dr. Campochiaro has received grants for clinical research from Genentech, the maker of ranibizumab. Dr. Massin has disclosed financial interests or relationships with Eli Lilly, Fovea Pharmaceuticals, Novartis, Solvay, and Takeda. Dr. Lim has received grants for educational activities from Genentech, and she has served on advisory boards and speakers bureaus for Genentech, Pfizer, Allergan, and Novartis.

2008 Joint Meeting of the American Academy of Ophthalmology (AAO) and the European Society of Ophthalmology (SOE): Scientific Session PA015 and PA016. Presented November 9, 2008.

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