Results from an analysis of pooled data from two, three-year phase 3 trials showed that Ruboxistaurin ( Arxxant ) reduced the risk of sustained moderate vision loss by 41 percent when compared to placebo in patients with moderate to severe, nonproliferative diabetic retinopathy. Vision loss occurred in only 6.1 percent of patients treated with Ruboxistaurin compared to 10.2 percent of patients treated with placebo.

Ruboxistaurin limits protein kinase C beta ( PKC beta ) overactivation, and it is the first of a new class of compounds being investigated for the treatment of diabetic retinopathy.

The laboratory of George L. King, at Joslin Diabetes Center, first proposed that PKC beta activation is responsible for the development of diabetic retinopathy and other microvascular damages induced by diabetes.

The combined analysis examined a total of 813 patients treated with 32 mg per day of Ruboxistaurin ( n=412 ) or placebo ( n=401 ) derived from two multi-center, randomized, placebo-controlled, double-masked, phase 3 trials that were similar in design and implementation.
The analysis examined whether Ruboxistaurin could reduce the risk of long-term, or sustained moderate vision loss caused by diabetic retinopathy.
Patients had moderate to severe nonproliferative diabetic retinopathy at the start of the study.
The beneficial effect of ruboxistaurin was not accompanied by a reduction in the progression of study patients from nonproliferative to proliferative diabetic retinopathy.

Vision loss ( measured in the study as sustained moderate vision loss ) occurred in only 6.1 percent of patients treated with Ruboxistaurin compared to 10.2 percent of patients treated with placebo, equaling a 41 percent relative risk reduction ( P=0.011 ) over three years.
Vision loss was defined as a three-line loss on the eye chart that was sustained for at least 6 months.

A separate analysis of data from 11 studies, of the safety of 32 mg per day of Ruboxistaurin in patients with at least one diabetic microvascular complication ( including diabetic retinopathy ), found Ruboxistaurin was generally well tolerated and had an overall adverse event profile, as well as a serious adverse event profile similar to placebo.
Serious adverse events occurred in 23.2 percent of patients taking placebo compared to 20.8 percent of patients taking Ruboxistaurin.
In addition, Ruboxistaurin had no effect on glucose or blood pressure control.
This data presentation reported on a clinical safety data base which includes a total of 2,804 patients with type 1 or type 2 diabetes combined from 11 phase 2 and 3 placebo-controlled, double-masked trials, for up to four years.
The only treatment-emergent adverse event that occurred with a frequency of greater than or equal to two percent and occurred significantly more often in the ruboxistaurin group was indigestion.

Diabetic retinopathy is a relatively common microvascular complication in individuals with diabetes that can lead to a sudden and debilitating impact on vision.
In the United States, an estimated 4.1 million adults aged 40 and older have diabetic retinopathy ( 40.3% of persons with diabetes mellitus) with 899,000 having vision-threatening retinopathy ( 8.2% ).
For persons with type 1 diabetes, the crude prevalence of diabetic retinopathy is about 80%.

Source: 66th Annual Scientific Sessions - American Diabetes Association ( ADA ), 2006


XagenaMedicine2006