Abstract

DO.02.10

GS-101 eye drops, an antisense oligonucleotide against IRS-1, inhibit and regress corneal neovascularization: interim results of a multicentre double-blind randomized phase II clinical study

Cursiefen C.¹, Kruse F.¹, Bock F.¹, Wilhelm F.², Schirra F.³, Seitz B.⁴, Meller D.^5
1Department of Ophthalmology, University of Erlangen-Nürnberg, Erlangen; ²Helios Eye Hospital Schwerin; ³Department of Ophthalmology, University of Saarland, Homburg; ⁴Department of Ophthalmology, University of Essen, Essen

Objective: Pathologic corneal blood vessels constitute the strongest preoperative risk factor for subsequent immune rejections. 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 neovascularisation.
Methods: The interim analysis of this multicentre double-blind randomized phase II clinical study was performed on 40 patients with progressive corneal neovascularisation due to different underlying diseases: 4 groups of 10 patients were treated in the dose finding study comparing 3 doses of GS-101 to placebo (eye drops: 2x/d). The degree of corneal neovascularisation 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 0.86 mg/ml (43µg /drop) produced a statistically significant regression of the corneal neovascularization together with an inhibition of progression and an improvement of the visual acuity (p=0.0047). Compared to the placebo group with 100% progression of corneal neovascularisation and no regression, 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 favour of the active drug versus placebo was observed in each treatment group. Regression of corneal neovascularization was significant in the group receiving 86 µg/d. 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.

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