A protein kinase C-beta inhibitor reduced the risk of sustained vision loss and progression of diabetic macular edema in two phase III trials, researchers announced. Ruboxistaurin (proposed name Arxxant; Eli Lilly and Company), decreases levels of protein kinase C (PKC) that are released in response to low blood glucose levels. PKC, particularly the beta form, is associated with increased vascular permeability, impaired contractility and increased angiogenesis.
In a meta-analysis of the two studies involving a total of 813 patients with moderate to severe diabetic retinopathy, ruboxistaurin reduced vision loss by 41%, Dr. Lloyd Paul Aiello of Harvard’s Joslin Diabetes Center in Boston, Massachusetts, reported.
“A moderate degree of retinopathy would reduce vision from 20/20 to around 20/40. For those with already impaired vision, this is a significant impact,” Dr. Aiello stated.
The researchers analyzed findings in 412 patients on ruboxistaurin 32 mg/d and 401 patients randomized to placebo. Total vision loss occurred in 6.1% of patients on active treatment compared with 10.2% on placebo, for a relative risk reduction of 41%.
In analysis of another 11 studies on the safety of ruboxistaurin, the drug had an adverse event rate equal to placebo. Serious adverse events occurred in 23.2% of patients on placebo and in 20.8% on ruboxistaurin. The only significant treatment-related adverse event was gastrointestinal upset in about 2% of patients on the drug.
Active treatment had no effect on glucose levels of blood pressure.
“The need for laser surgery to treat macular degeneration is reduced,” Dr. Aiello said. “There is no wearing off (of effect). It theoretically would be used as maintenance therapy in diabetics with retinopathy.”
The investigators have submitted a NDA to the US Food and Drug Administration, and the FDA says they have fast-tracked the drug. “Now, we’re just waiting to hear,” Dr. Aiello said.
He noted that approximately 40% of all diabetics and around 80% of type 1 diabetics develop some degree of retinopathy. In 8.2% of cases, vision is affected.
Reported at the 66th Scientific Sessions of the American Diabetes Association.