Source: Neuroimaging Clin N Am  |  Posted 6 years ago

By Earl R. Nichols

CHICAGO, IL -- October 24, 2005 -- An investigational drug that could lead to markedly reduce vision loss in people with diabetic eye disease was previewed here at the annual meeting of the American Academy of Ophthalmology (AAO).

The drug is also being investigated in the treatment of microvascular complications arising from type 1 and type 2 diabetes.

Presenter Lloyd Aiello, Principal Investigator and Professor of Medicine, Harvard Medical School, Boston, Massachusetts, United States, said diabetic retinopathy is the leading cause of blindness in working-age adults in the United States, leading to as many as 24,000 new cases of blindness each year.

The new drug, ruboxistaurin mesylate (RBX), is a protein kinase C beta inhibitor, the first of a new class of compounds being investigated for the treatment of diabetic retinopathy and diabetic peripheral neuropathy. The agent blocks activation of cell signaling molecules that lead to altered gene expression and altered protein function, both of which are implicated in abnormal angiogenesis, blood flow and hyperpermeability in the microvessels of the eye.

In the phase 3 study presented here on October 14[^]th[] at the AAO meeting, 685 subjects were randomized to receive oral RBX at a dose of 32 mg/day or daily placebo. Subjects were followed for a minimum of 3 years.

A total of 258 and 256 subjects in the RBX group and the placebo group completed the study, respectively. The researchers studied a total of 599 eyes in the RBX group and 584 eyes in the placebo group.

Patients at baseline had at least one eye with best-corrected vision of 45 or more letters on the Early Treatment Diabetic Retinopathy Studies visual acuity protocol, which corresponds to vision of 20/125, or they had moderately severe to very severe non-proliferative diabetic retinopathy. Subjects in the study had not received prior panretinal photocoagulation but had had focal or grid photocoagulation.

The primary outcome demonstrated a decrease in sustained moderate vision loss of 5.5% in the RBX group and 9.1% in the placebo group. Patients receiving RBX maintained visual acuity above baseline, around 77.5 to 78.0 letters, while those in the placebo group lost approximately 2.6 letters (P = .011)

Approximately 5% of eyes in the study group gained 15 or more letters, while 2% of eyes in the placebo group achieved this endpoint, Dr. Aiello said.

There were no differences between groups in terms of time to patient discontinuation of treatment, use of photocoagulation or progression of diabetic retinopathy.

According to Dr. Aiello, RBX treatment had no impact on progression of diabetic retinopathy, but it was associated with a delay in moderate and sustained moderate vision loss. Treatment also delayed the progress of diabetic macular edema to within 100 microns of the centre of the macula in eyes that already had clinically significant macular edema at baseline, he said.

REFERENCE:
Aiello L., et al. for the PKC-DRS Study Group. The effect of ruboxistaurin on visual loss in patients with moderately severe to very severe nonproliferative diabetic retinopathy: initial results of the Protein Kinase C beta Inhibitor Diabetic Retinopathy Study (PKC-DRS) multicenter randomized clinical trial. Diabetes. 2005 Jul;54(7):2188-97.

[Presentation title: Protein Kinase C-Beta Inhibitor - Diabetic Retinopathy Study 2 (PHC-DRS2): A Phase III Clinical Trial.]