Sustained Release ROCK Inhibitor/Protein Kinase C Inhibitor Implant
AR-13503 (the active metabolite of netarsudil) is an investigational compound discovered by Aerie scientists. It has not been approved by the U.S. Food and Drug Administration (FDA). An inhibitor of Rho kinase (ROCK) and Protein kinase C (PKC), AR-13503 has the potential to provide an entirely new mechanism and pathway for the treatment of wet age-related macular degeneration (AMD), diabetic retinopathy, and related diseases of the retina.
How AR-13503 is Thought to Work
AR-13503 inhibits both ROCK and PKC, two related protein kinases that are thought to contribute to multiple disease processes associated with retinal diseases. In preclinical models of retinal disease, inhibitors of ROCK have been shown to reduce neovascularization, blood-retinal barrier breakdown/edema, inflammation, fibrosis and neuronal dysfunction.1, 2
In a preclinical model of proliferative diabetic retinopathy, AR-13503 produced highly significant reductions in total neovascular area and demonstrated additive efficacy when combined with the current market-leading anti-vascular endothelial growth factor (VEGF) product.3 AR-13503 also has demonstrated efficacy as monotherapy in a preclinical choroidal neovascularization model of wet AMD.4 These experiments suggest that with its novel mechanism of action, AR-13503 has potential as monotherapy and also as an adjunct to anti-VEGF therapies.
Preclinical results: AR-13503 provides additive efficacy to aflibercept (Eylea®) in a model of diabetic retinopathy1
For more information on Eylea please see the product webpage
AR-13503 Sustained Release (SR) has been formulated for intravitreal injection as a small, bio-erodible implant (utilizing a polymer developed by DSM, a global, science-based company with whom we have entered a collaborative research, development, and licensing agreement) to provide sustained drug delivery to the back of the eye. Preclinical results have shown linear, sustained elution rates over several months and achievement of target retinal drug concentrations.5, 6
Aerie filed an Investigational New Drug (IND) application for AR-13503 SR Implant in March 2019. A first-in-human clinical study in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) was initiated in August 2019. We are currently in the process of completing this Phase 1 study and evaluating potential opportunities for other indications beyond DME and nAMD.
- Bhutto and Lutty, Mol Aspects Med 33: 295-317 (2012).
- Shin et al., J. Ophthalmic Vis Res 9: 362-373 (2014).
- Carbajal et al., Invest. Ophthalmol. Vis. Sci. 2018;59(9): 200.
- Ding et al., Invest. Ophthalmol. Vis. Sci. 2018;59(9):205.
- Glendenning et al., Invest. Ophthalmol. Vis. Sci. 2018;59(9):5672.
- Ding et al., Invest. Ophthalmol. Vis. Sci. 2019;60(9):5387.