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Michael Karl Boettger, Juergen Klar, Annett Richter, Georges von Degenfeld; Topically administered regorafenib eye drops inhibit grade IV lesions in the non-human primate laser CNV model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2294.
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Intravitreal injections are clinically used to administer approved protein therapeutics directed against VEGF to the retina. The non-human primate laser CNV model is considered a disease-relevant model for testing therapeutic approaches for the treatment of wet AMD. In this model, both ranibizumab and aflibercept significantly reduced so-called grade IV lesions (semiquantitative measure of relevant vascular leakage from the laser lesions), which are considered as a surrogate for active wet AMD in humans. Here, we examined the efficacy of regorafenib, a multi-kinase inhibitor targeting VEGFR2 (KDR), administered topically as eye drops in the same model.
Non-human primates’ eyes were exposed to laser and Bruch’s membrane was ruptured in order to generate a back of the eye phenotype as seen in wet age-related macular degeneration with retinal edema caused by vascular leakage. Starting 4 hours after laser, animals were treated with regorafenib eye drops (concentration 20 mg/mL, BID) for three weeks. Data were compared to animals receiving vehicle eye drops or ranibizumab (0.5 mg, intravitreal injection 4 hours after lasering). Leakage was graded using fluorescein angiographies on day 21 after laser.
Similar to intravitreally administered ranibizumab, a significantly reduced occurrence of grade IV lesions was observed in regorafenib eye drops treated animals: 21±18% (mean±SD) grade IV lesions in vehicle controls (n=23) versus 7±13% in animals treated with regorafenib eye drops (n=16; p = 0.013). No adverse reactions were observed in any of the animals treated.
Currently available treatment options require injection(s) into the eye by a physician. An eye drop formulation would be non-invasive and self-administered by patients. Regorafenib eye drops show efficacy in the non-human primate laser CNV model.
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