GS-101 effective in inhibiting and regressing corneal neovascularisation

Halsin PartnersSep 1 2009

Data published in Ophthalmology show GS-101 may prevent corneal graft rejection

Gene Signal, a company focused on developing innovative drugs to manage angiogenesis based conditions, today announced the publication of interim results from a phase II study suggesting that the antisense oligonucleotide GS-101 (eye drops) is safe and effective at inhibiting and regressing corneal neovascularisation (abnormal new blood vessel growth). Neovascularisation in this part of the eye is a major risk factor in corneal graft rejection, the most common transplantation procedure that saves the sight of approximately 46,000 people worldwide each year.

The data were published in the September 2009 issue of Ophthalmology by researchers led by Claus Cursiefen, MD, from the Department of Ophthalmology at the Friedrich-Alexander University Erlangen-N-rnberg, in Erlangen, Germany. Gene Signal is now conducting an international phase III trial with GS-101 for the prevention of pathologic corneal neovascularisation and thereby corneal graft rejection. GS-101 has been granted Orphan Drug status for this indication in Europe.

"Compared to the placebo group in which 100% of patients suffered from progression of corneal neovascularisation, the optimal GS-101 treatment group showed regression in 86% of patients. We are very encouraged by these results as they represent real progress in the development of GS-101 as a new treatment to combat corneal graft rejection," explained Dr. Claus Cursiefen of the Department of Ophthalmology, Friedrich-Alexander University Erlangen-N-rnberg. "We urgently need new options for the thousands of graft recipients, whose current treatment options for threatened rejection such as immunosuppressants are not ideal due to side effects. GS-101 is the first specific angiogenesis inhibitor that has demonstrated activity at the anterior part of the eye, where numerous diseases associated with pathologic angiogenesis endanger vision."

"The publication of these positive phase II results for GS-101 is a major milestone for Gene Signal. As a novel approach to the management of ophthalmic angiogenesis, we are keen to provide rigorous scientific backup to support our ongoing clinical development program. We also recently published data in the Journal of Pharmacology and Experimental Therapeutics confirming that GS-101 prevents in vivo expression of IRS-1, a protein associated with new blood vessel formation (angiogenesis), and we intend to present additional data on GS-101 at various scientific forums in the near future," noted Eric Viaud, CEO of Gene Signal.

The aim of this randomised, double-blind, multicenter phase II clinical study was to test the efficacy and tolerability of GS-101 (eye drops), an antisense oligonucleotide against insulin receptor substrate-1 (IRS-1), versus placebo, against progressive corneal neovascularisation (excessive or harmful angiogenesis). Forty patients non-responsive to conventional therapy participated in the study. Four groups of 10 patients were treated for three months comparing three doses of GS-101 (eye drops: 2x/day; 43, 86 and 172 g/day total) to placebo (10 patients per group). The primary endpoint was measured by the reduction in area covered by pathologic corneal blood vessels measured morphometrically on digitised slit-lamp pictures using image analysis techniques.

Treatment with GS-101 was generally well tolerated, with no associated serious side effects. At 86 micro g/day GS-101 eye drops produced a significant inhibition and regression of corneal neovascularisation (-2.04 -1.57% of total corneal area;>