Purpose: Pathologic corneal neovascularization constitutes the strongest preoperative risk factor for subsequent immune rejections. The aim of this study was to test the efficacy and tolerability of three doses of GS-101 eye drops, an antisense oligonucleotide against IRS-1, versus placebo, on inhibition of corneal neovascularization.

SETTING: The interim analysis of this multicentre double-blind randomized phase II clinical study was performed on 40 patients with progressive corneal neovascularization due to different underlying diseases: 4 groups of patients were treated in this dose finding study comparing 3 doses of GS-101 (eye drops: 2x/day; 43, 86 and 172µg/day total) to placebo.

METHODS: The degree of corneal neovascularization was assessed using semiautomatic image analysis and morphometry on standardized corneal slit-lamp pictures taken at defined intervals during treatment (up to three months). All patients were regularly examined ophthalmologically for adverse events and side-effects.

RESULTS: GS101 eye drops at the dose of 86µg /day (43 µg/drop) produced a highly significant regression of the corneal neovascularization (p=0.0047) together with a trend of an improvement of visual acuity Compared to the placebo group with 100% ongoing progression of corneal neovascularisation over the 3-month period, the optimal treatment group achieved 86% regression and progression in only 14%. Fifty-seven (57) adverse events were reported in 21 patients, most of them unrelated or unlikely related to the study drug. Eight (8) unrelated serious adverse events were reported in 6 patients.

CONCLUSIONS: A positive difference in favor of the active drug versus placebo was observed in each treatment group. Regression of corneal neovascularization was significant in the group receiving 86 µg/day with no additional benefit at the highest dose. Study treatments were well tolerated. These interim results of a phase II study suggest GS101 eye drops to be an effective and safe approach to specifically inhibit and regress active corneal neovascularization, a major risk factor for corneal graft rejection. Financial disclosure: Support by Gene Signal, France.