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L. Cheng, A. Tammewar, I. Falkenstein, H.-X. Li, F. Wong-Staal, W. R. Freeman; Intraocular Anti-Angiogenic and Antiproliferative Properties of IMS 2186, a Long Lasting Intravitreally Injectable Non-Steroid Small Molecule. Invest. Ophthalmol. Vis. Sci. 2007;48(13):103.
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© ARVO (1962-2015); The Authors (2016-present)
To report the intraocular properties and efficacy of a novel compound, IMS 2186, for the treatment of choroidal neovascularization. IMS 2186 was chosen from a family of compounds with properties that were determined to be useful in the intravitreal treatment of choroidal neovascularization in age related macular degeneration. The drug is a non-steroid small molecule (MW 296) which is sparingly soluble in water and which is expected to dissolve slowly in the vitreous. It has in vitro anti-poliferative, anti-migratory, anti-angiogenic, and anti-inflammatory properties.
IMS 2186 was first injected into rabbit eyes at a dose of 2.5 mg per 0.05 cc and evaluated for up to 40 weeks. A homogenously micronized formulation of the compound was used to treat laser induced CNV in Brown Norway Rats. The efficacy was evaluated compared to vehicle, triamcinolone, and a control negative compound.
There was no toxicity over a 36-week observation period. The drug was still visible at that time. Slit lamp, indirect ophthalmoscopy and light microscopy, IOP measurements, as well as electroretinography revealed no toxicity of the drug. Results of CNV treatment of 175 laser lesions revealed a reduction of fluorescein angiographic leakage. Analysis using confocal microscopy revealed lesion vascularity as measured by FITC- isolectin staining was reduced compared to control (p=0.045) with the inhibition magnitude being 26%. Total cellularity (i.e. proliferation) in the lesions as measured by dapi staining was also reduced by IMS 2186 by a factor of 40% (p<0.00003). This effect appeared stronger than the triamcinolone effect.
IMS 2186 is a long acting intravitreally injectable compound without toxicity at the doses used. It can be used as a repository intravitreal injection and has strong activity against proliferation and endothelial cell invasion in laser induced CNV. Clinically, it may prove useful as an adjunct to LucentisTM or other anti-angiogenic therapies and will have a much reduced injection frequency.
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