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VEGF Small Interfering RNA (Cand5) for the Treatment of Diabetic Macular Edema
Diabetic Retinopathy Highlights from Retina/Vitreous Free Papers
| Sunday, November 12, 2006 |
| Jonathan Prenner, MD, RACE Study Group
Cand5, now known as bevasiranib, represents a different approach to vascular endothelial growth factor (VEGF) inhibition than that used by pegaptanib, bevacizumab, and ranibizumab. Bevasiranib is an intracellular VEGF inhibitor, while the other agents are extracellular VEGF inhibitors. Recalling that one of the effects of VEGF is to increase vascular permeability, the difference in these two approaches can be likened to that taken by janitors and plumbers confronted with a leaking faucet. A janitor mops up the water on the floor, an action which quickly removes the water but does not fix the leak. To keep the floor dry, the janitor will have to mop repeatedly; extracellular VEGF inhibitors are like janitors. By contrast, a plumber fixes a leaking faucet, stopping the flow of water at its source, offering a prolonged benefit but requiring more time to perform than mopping the floor. This is analogous to the potential benefit of an intracellular VEGF inhibitor.
Dr Prenner reported the results of an uncontrolled study of 48 patients with either type 1 or type 2 diabetes randomized 3:2:3 to 3 intravitreal injections of 0.2 mg, 1.5 mg, and 3.0 mg Cand5 administered once every 4 weeks. 31% of eyes had previously been treated with intravitreal steroids and had recurrence of diabetic macular edema (DME). 58% of eyes had severe DME according to International Clinical DME Severity Scale standards. Mean baseline best-corrected visual acuity (BCVA) was <20/80-2 in 33% of eyes.
Increased iritis was the most frequently observed adverse event, but Cand5 appears to be safe and well tolerated, with no serious adverse events. Little change in BCVA and central retinal thickness were noted at 12 weeks, but a lag in effect was expected. Subjectively, anatomical appearance did improve. Dr Prenner concluded that a larger study of longer duration is needed to assess the efficacy of Cand5.
Dr Bressler noted that the results could be explained by either a time lag or lack of drug efficacy, and suggested that the investigators test a small number of patients to determine which is happening. Dr Haller asked whether there might be a biologic signal that could be used to indicate whether the drug was working. Dr Avery suggested extending the study to see how patients fared longer term. |
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