Phase 3 studies show ranibizumab prevents vision loss in wet AMD patients

Two phase 3 clinical studies of ranibizumab show that the drug prevents vision loss in more than 90% of patients who have exudative age-related macular degeneration.

Philip J. Rosenfeld, MD, PhD, of Bascom Palmer Eye Institute in Miami and colleagues at several centers in the United States conducted the double-blind, controlled study, called the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD (MARINA) study.

Researchers randomized 716 patients to receive either 0.3 mg or 0.5 mg of ranibizumab (Lucentis, Genentech) or placebo injections once monthly over 2 years. All patients had minimally classic or occult choroidal neovascularization (CNV), according to the study.

At 2 years' follow-up, investigators found that 90% of ranibizumab-treated patients maintained vision, defined as a loss of less than 15 letters of visual acuity (VA). In contrast, 53% of placebo-treated patients maintained vision.

Additionally, 24.8% of 0.3 mg-treated patients and 33.8% of 0.5 mg-treated patients gained at least 15 letters of VA, vs. 5% of the control group (P < .001). Patients receiving 0.3 mg of ranibizumab gained an average 5.4 letters of vision, and those receiving 0.5 mg gained an average 6.6 letters. In contrast, placebo-treated patients lost an average 14.9 letters of VA, according to the study.

"What makes this publication particularly significant is that the MARINA study was the first phase 3 study for wet AMD to show visual improvement in the average patient after 1 year of treatment and this benefit was maintained through 2 years and associated with anatomic improvements that further confirm the effectiveness of ranibizumab," Dr. Rosenfeld said in a press release.

The MARINA study also found low rates of serious adverse events. Five ranibizumab-treated patients (1%) developed presumed endophthalmitis and six ranibizumab-treated patients (1.3%) developed serious uveitis. However, the drug showed no long-term effect on IOP, according to the study.

The 1-year results of a second ongoing phase 3 study, the Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD (ANCHOR) study, also support the benefits of ranibizumab treatment.

The ANCHOR study is being led by David M. Brown, MD, of Vitreoretinal Consultants in Houston. It includes 423 patients randomized to receive 0.3 mg or 0.5 mg of ranibizumab along with sham verteporfin photodynamic therapy (PDT) or sham injections plus active verteporfin PDT. Treatments are performed monthly, and investigators continue to follow patients to 2 years. All patients exhibit classic CNV.

At 1 year, 94.3% of the 0.3 mg ranibizumab group and 96.4% of the 0.5 mg group lost less than 15 letters of vision compared to 64.3% of control patients (P < .001), according to the study.

Visual acuity improved 15 or more letters in 35.7% of 0.3 mg ranibizumab-treated patients and 40.3% of the 0.5 mg group. Mean VA increased 8.5 letters in 0.3 mg group and 11.3 letters in 0.5 mg group.

For the control group, mean VA decreased by 9.5 letters. Only 5.6% of control patients improved at least 15 letters, according to the study.

The ANCHOR study found rates of ocular adverse events similar to the MARINA study, although there was a higher proportion of patients with post-injection IOP of 30 mm Hg or more.

Preliminary 2-year results from the ANCHOR study are expected in the first quarter of 2007.

Both studies are published in the Oct. 5 issue of the New England Journal of Medicine.