Netarsudil: A Comprehensive Pharmacological and Clinical Monograph

1.0 Abstract and Overview

Netarsudil is a first-in-class ophthalmic medication approved for the reduction of elevated intraocular pressure (IOP) in adult patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).[1] As a small molecule amino-isoquinoline amide, its primary distinction lies in a novel, multi-faceted mechanism of action that directly targets the conventional aqueous humor outflow pathway, the principal site of pathological resistance in glaucoma.[1] Netarsudil functions as a dual inhibitor of Rho-associated protein kinase (ROCK) and the norepinephrine transporter (NET).[1] This dual inhibition produces a triple-action effect on aqueous humor dynamics: (1) it enhances trabecular outflow by inducing relaxation of the trabecular meshwork cells; (2) it is believed to decrease aqueous humor production by reducing blood flow to the ciliary body; and (3) it lowers episcleral venous pressure (EVP).[2]

Pivotal Phase 3 clinical trials, including the ROCKET-1 and ROCKET-2 studies, established the efficacy of a 0.02% ophthalmic solution of netarsudil administered once daily. These trials demonstrated that netarsudil was non-inferior to the beta-blocker timolol 0.5% in reducing IOP in the key patient population with baseline pressures below 25 mmHg.[3] A notable characteristic of netarsudil is its ability to lower IOP consistently across a range of baseline pressures, suggesting potential utility in conditions such as normal-tension glaucoma.[3]