Name: Aganirsen

About antisense oligonucleotides: Antisense oligonucleotides are small complementary nucleotide segments, which bind to and silence mRNA, thereby inhibiting the transcription of a particular protein. Thanks to the small molecular size of the oligonucleotide, they hold many advantages over other biologics which are normally larger proteins or monoclonal antibodies. Antisense oligonucleotides have the ability to readily diffuse across cell membranes, have low immunogenicity and can be produced by simple chemical synthesis, without the need for a complex biological production process.

Aganirsen (GS-101), is a novel antisense oligonucleotide, which acts by inhibiting transcription of insulin receptor substrate 1 (IRS-1) which is over-expressed in pathological angiogenesis. IRS-1 in turn stimulates the production of VEGF-1, a well-known promotor of neovascularization. Unlike inhibiting VEGF-1 however, reducing IRS-1 has been demonstrated to target pathological vessels specifically, without inhibiting normal vessel growth. Contrary to other products which need to be injected into the eye, Aganirsen is administered topically by the patients themselves, as an eye-drop. Depending on the formulation, the substance is indicated primarily for the front (cornea) or back of the eye (retina).
GS-101 is initially being developed for the treatment of corneal graft rejection as the first indication. In the I-CAN Phase III trial, the first randomized trial of a topical inhibitor of corneal angiogenesis, aganirsen was shown to be safe and well-tolerated and to significantly reduce the relative area of corneal neovascularisation, reducing the need for corneal transplantation in patients suffering from viral keratitis and central neovascularization. The study results were published in the journal Ophtalmology. A confirmatory trial will be started in 2016. The product is also planned to be investigated in a Phase II trial for the treatment of ischemic central retinal vein occlusion (iCRVO) as well  as a Phase II trial in age-related macular degeneration (AMD) and diabetic macular oedema (DME).
The product holds four orphan drug designations in Europe, for the Prevention of Corneal Graft Rejection, treatment of Neovascular Glaucoma, Ischemic Central Retinal Vein Occlusion and Retinopathy of Prematurity.

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