Ranibizumab Recommended for Diabetic Macular Edema

Troy Brown

July 26, 2012

July 26, 2012 — An advisory committee to the US Food and Drug Administration (FDA) recommended approval of ranibizumab (Lucentis, Genentech, Inc) injection, dosed monthly, for the treatment of diabetic macular edema. The committee voted unanimously to recommend the 0.3 mg dose, and 8 to 2 voted in favor of recommending the 0.5 mg dose.

"I'm very excited, having had patients go blind and not having a way to treat them. This is a really big moment," said committee member Susan M. MacDonald, MD, director of Comprehensive Ophthalmology and assistant professor at Tufts University School of Medicine in Boston, Massachusetts, at the meeting.

Ranibizumab is given by intravitreal injection and is currently approved for use in the treatment of neovascular (wet) age-related macular degeneration and macular edema following retinal vein occlusion (RVO). It decreases retinal edema by blocking vascular endothelial growth factor-A (VEGF-A) in the eye and decreasing retinal capillary permeability.

Diabetic macular edema is a leading cause of vision loss and blindness in the United States. The current standard of care is laser surgery, which can slow the progression of vision loss but has little ability to restore lost vision.

The committee discussed data from a phase 3, double-masked, multicenter, randomized, sham injection–controlled parallel-group study of ranibizumab injection in patients with clinically significant diabetic macular edema. The data come from 2 identically designed studies — Study FVF4168g (RIDE) and Study FVF4170g (RISE).

Together, these studies examined 759 patients who were randomly assigned to receive monthly treatment with 0.3 mg Lucentis injection, 0.5 mg Lucentis injection, or sham injection (control group) in 1 treatment eye. Primary outcomes were measured at 24 months, after which patients in the control group were allowed to cross over to receive 0.5 mg ranibizumab monthly; all patients were followed for 36 months.

The primary efficacy measure for both studies was the proportion of patients who could read at least 15 additional letters (about 3 lines) on the standardized eye chart compared with what they were able to read at the beginning of the study.

According to pooled results from both studies, 39.2% of patients who received 0.3 mg ranibizumab and 42.5% of patients who received 0.5 mg ranibizumab gained at least 15 letters from baseline in best corrected visual acuity (BCVA) score at 24 months, compared with 15.2% of patients in the sham group. These results were statistically significant (P < .0001 for each dose group vs the sham group), and the benefit over sham was demonstrated in both studies, beginning 1 month after the first treatment.

At month 36, pooled data showed that the average BCVA score increased from baseline by 12.4 letters in the 0.3 mg group, 11.2 letters in the 0.5 mg group, and 4.5 letters in the sham group.

Safety

In all, 250 patients were included in each of the treatment groups and in the sham group. Of these, 3 (1.2%) patients in the sham group, 7 (2.8%) patients in the 0.3 mg group, and 11 (4.4%) patients in the 0.5 mg group died.

Myocardial infarction occurred in 9 (3.6%) of the patients in the sham group, 9 (3.6%) of the patients in the 0.3 mg group, and 7 (2.8%) of the patients in the 0.5 mg group.

Stroke occurred in 4 (1.6%) participants in the sham group, 3 (1.2%) participants in the 0.3 mg group, and 8 (3.2%) participants in the 0.5 mg group.

Causes of death were consistent with those expected in patients with complications from advanced diabetes, but the exact relationships between ranibizumab and the fatal events are unclear.

"As retina specialists, we use anti-VEGF agents all day, every day now…so I'm pretty comfortable with it," said committee member William B. Phillips II, MD, an ophthalmologist at The Retina Group of Washington in Clinton, Maryland.

"We do not need additional studies for the approval — in fact, I would urge approval as soon as possible, to help the patients who are involved," said committee member Lynn K. Gordon, MD, PhD, professor of ophthalmology at Jules Stein Eye Institute, and associate dean in diversity affairs at David Geffen School of Medicine at the University of California at Los Angeles, in Los Angeles, California.

A nonvoting committee member is employed by Forest Research Institute. No other relevant financial relationships were disclosed.

US Food and Drug Administration (FDA), Dermatologic and Ophthalmic Drugs Advisory Committee (DODAC) Meeting, July 26, 2012.

FDA Briefing Ranibizumab

Genentech Briefing Lucentis (Ranibizumab)

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