Ruboxistaurin may prevent visual loss from diabetes

The availability of new therapeutic tools has become especially important when considering the increasing numbers of patients who are expected to develop the disease.

"Diabetes is a major problem affecting millions of people worldwide," said Dr. Aiello, associate professor of ophthalmology, Harvard Medical School, and investigator and head of eye research, Joslin Diabetes Center, Boston. "By 2030, it is estimated that more than 370 million individuals will develop diabetes. Diabetic retinopathy is now the leading cause of vision loss in developed countries, with the majority of vision loss resulting from diabetic macular edema."

A number of studies have evaluated this hypothesis, two of which were phase III studies that evaluated the investigational drug ruboxistaurin, which is an oral PKC-beta inhibitor. The PKC-DRS study enrolled 252 patients and was complete in 2002. The second study, the PKC-DRS2 study, was a multicenter, randomized, double-masked, parallel, placebo-controlled trial that enrolled 685 patients with type 1 or type 2 diabetes and was completed late in 2005, Dr. Aiello said.

During the PKC-DRS study, ruboxistaurin did not have an effect on the primary endpoint, which was progression of the level or severity of nonproliferative diabetic retinopathy, he pointed out.

"However, when the investigators evaluated the secondary endpoint of vision loss, there was a 35% risk reduction in moderate vision loss in the patients randomly assigned to ruboxistaurin compared with those who received placebo," Dr. Aiello explained. As a result the PKC-DRS2 study evaluated visual acuity in more than five times the number of patients in each treatment arm as in the first study.

The patients in the PKC-DRS2 were randomly assigned to receive placebo (340 patients) or oral ruboxistaurin (32 mg/day) (345 patients). At least one eye of each patient had a best-corrected visual acuity of 20/125 or better and moderately severe to very severe nonproliferative diabetic retinopathy to be included in the study. The primary endpoint of the study was sustained moderate vision loss of 15 letters or greater. None of the patients had undergone previous panretinal photocoagulation, had glaucoma, or a recent intraocular surgery but could have had previous focal photocoagulation for diabetic macular edema.

Preserving vision

"During the course of the PKC-DRS2 study, 9.1% of the patients in the placebo group experienced sustained moderate vision loss compared with 5.5% in the group treated with ruboxistaurin," Dr. Aiello said. "This difference was a 40% risk reduction of moderate vision loss with ruboxistaurin during the course of the study."

Importantly, the patients treated with the drug also had a more than doubling of the chance of having a 15-letter or greater gain in vision over the course of the study.

For those patients who had not been treated with photocoagulation before the study, the chances of needing focal photocoagulation were reduced by 29% if they were randomly assigned to receive ruboxistaurin. If the patients needed focal photocoagulation during the study, the patients receiving ruboxistaurin had less visual loss subsequent to the focal photocoagulation than the patients who received placebo and underwent focal photocoagulation.

In addition, the drug had a good safety profile. To date, more than 2,000 patients with diabetes have been treated with ruboxistaurin for up to 3 years.