General Information

Lucentis (ranibizumab) is a therapeutic antibody fragment designed to inhibit vascular endothelial growth factor A (VEGF-A), a protein that plays a critical role in ocular angiogenesis. Blocking VEGF-A can decrease abnormal new blood vessel formation and the resultant leaking of serum into the retina.

Lucentis is specifically indicated for diabetic macular edema.

Lucentis is supplied as a solution for intravitreal injection. The recommended dose of Lucentis for diabetic macular edema is 0.3 mg (0.05 mL of 6 mg/mL solution) administered once a month (approximately 28 days).

Clinical Results

FDA Approval
The FDA approval of Lucentis for diabetic macular edema was based on two randomized, double-masked, three-year studies, DME1 and DME2. A total of 759 subjects were enrolled and received Lucentis 0.3 mg (n=250); Lucentis 0.5 mg (n=252) or placebo (n=257); 582 (77%) subjects completed through Month 36. The studies were placebo controlled through Month 24. From Months 25 through 36, subjects who previously received placebo were eligible to receive monthly Lucentis 0.5 mg and subjects originally randomized to monthly Lucentis 0.3 mg or 0.5 mg continued to receive their assigned dose. The study was not designed to compare the two doses of Lucentis, but each dose against the control group. Compared to monthly Lucentis 0.3 mg, no additional benefit was observed with monthly treatment with Lucentis 0.5 mg. The data are from the 0.3 mg arm and were measured at Month 24. The results are as follows:
DME1
Gain of >15 letters in visual acuity: Lucentis 34%; placebo 12%
Loss of <15 letters in visual acuity: Lucentis 98%; placebo 92%
Mean change in visual acuity (letters): Lucentis 10.9; placebo 2.3
DME2
Gain of >15 letters in visual acuity: Luncentis 45%; placebo 18%
Loss of <15 letters in visual acuity: Lucentis 98%; placebo 90%
Mean change in visual acuity (letters): Lucentis 12.5; placebo 2.6

Visual acuity outcomes observed at Month 24 in subjects treated with Lucentis 0.3 mg were maintained with continued treatment through Month 36 in both DME studies. Subjects in the placebo arms who received Lucentis 0.5 mg beginning at Month 25 achieved lesser visual acuity gains compared to subjects who began treatment with Lucentis at the beginning of the studies.

Side Effects

Adverse events associated with the use of Lucentis for diabetic macular edema may include, but are not limited to, the following:

• conjunctival hemorrhage
• eye pain
• vitreous floaters
• increased IOP

Mechanism of Action

Lucentis (ranibizumab) is a recombinant humanized IgG1 kappa isotype monoclonal antibody fragment designed for intraocular use. Ranibizumab binds to and inhibits the biologic activity of human vascular endothelial growth factor A (VEGF-A). VEGF-A has been shown to cause neovascularization and leakage in models of ocular angiogenesis and vascular occlusion and is thought to contribute to pathophysiology of neovascular AMD, macular edema following RVO, and DME. The binding of ranibizumab to VEGF-A prevents the interaction of VEGF-A with its receptors (VEGFR1 and VEGFR2) on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation.

Literature References

Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L, Gibson A, Sy J, Rundle AC, Hopkins JJ, Rubio RG, Ehrlich JS; RISE and RIDE Research Group Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology 2012 Apr;119(4):789-801

Additional Information

For additional information regarding Lucentis or diabetic macular edema, please visit the Lucentis web page.