Glaucoma is a group of optic neuropathies in which a buildup of aqueous humor, the fluid that nourishes and cleanses the front of the eye, increases intraocular pressure (IOP), causing progressive damage to the optic nerve. Glaucoma is a leading cause of blindness in people over the age of 60. The most common form of the disease is primary open-angle glaucoma, in which the increase in IOP is related to a gradual decrease in the ability of the eye’s drainage system to allow aqueous humor to exit normally. Primary open-angle glaucoma usually has no symptoms and its effects on vision may not be noticeable for some time, giving it the nickname “silent thief of sight.” It is estimated that more than 3 million people in the United States have glaucoma but that only about half of them have been diagnosed.
Addressing the Need
Aerie was founded to pursue new treatments for open-angle glaucoma that address the underlying pathology of the disease, the stiffening of the eye’s principle drain for aqueous humor, the trabecular meshwork. Until recently, treatments available for lowering IOP in glaucoma either reduced the production of aqueous humor or shunted it out of the eye through the secondary uveoscleral pathway as their primary mechanisms of action.
The reduction of IOP remains the only therapeutic option for the treatment of glaucoma. There remains a need for therapies that can prevent glaucoma or restore vision lost to the disease. Those goals are the focus of ongoing research.
The Netarsudil Family
Aerie’s research resulted in the discovery and development of the ROCK inhibitor, netarsudil. ROCK inhibitors lower IOP by targeting the trabecular meshwork at the subcellular level, binding to the protein Rho kinase (ROCK). This disrupts the interaction of myosin with actin causing disassembly of actin stress fibers and anchoring complexes, thereby reducing fibrosis and relaxing the TM. 1,2 Netarsudil has also been shown to reduce episcleral venous pressure, a novel effect on the distal portion of the conventional outflow pathway that contributes to the lowering of IOP.3-5
Aerie currently markets two glaucoma treatments based on netarsudil in the United States, Rhopressa® (netarsudil ophthalmic solution) 0.02% and the fixed-dose combination Rocklatan® (netarsudil and latanoprost ophthalmic solution) 0.02%/0.005%. More information on these products, including complete prescribing information, is available here:
Both of these products, under the names Rhokiinsa® and Roclanda® , have been authorized in the EU and Great Britain.
Aerie, in collaboration with Santen Pharmaceutical Co., Ltd., has initiated a Phase 3 study of netarsudil in Japan. Under an exclusive license agreement, Santen will complete the Phase 3 program and commercialize Rhopressa® and Rocklatan® in Japan and eight other Asian countries.
The Next Frontier
Aerie has conducted initial preclinical studies to explore the potential that the ROCK inhibitor AR-13503, an active metabolite of netarsudil, may have a role in restoring the health of damaged retinal ganglion cells in glaucoma and potentially improving vision, a therapeutic approach called neuroenhancement. Current clinical evaluation of an AR-13503 sustained-release implant in retinal diseases will help determine the future of the glaucoma neuroenhancement program.
- Rao et al. Exp Eye Res. 2017;158:23.
- Lin et al. J OculPharmacol Ther. 2018;34:40.
- Kazemi et al. J Ocul Pharmacol Ther. 2018;345:380-386
- Kiel et al. J Ocul Pharmacol Ther. 2015;31:146-151
- Sit et al. Am J Ophthalmol. 2021 Jan 29;226:262-269