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Editors Selection IGR 14-4
Medical Treatment: Rho-kinase Phase 3 Trials
Comment by Robert Feldman on:
75444 Two Phase 3 Clinical Trials Comparing the Safety and Efficacy of Netarsudil to Timolol in Patients With Elevated Intraocular Pressure: Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2), Serle JB; Katz LJ; McLaurin E et al., American Journal of Ophthalmology, 2018; 186: 116-127
Rho kinase (ROCK) inhibitors are a new class of topical medications for elevated IOP. ROCK inhibitors lower IOP by increasing aqueous outflow through the trabecular meshwork. ROCK inhibitors decrease cellular contraction and rigidity and synthesis of fibrotic extracellular matrix proteins.1 Serle et al. describe two studies, with the purpose of evaluating the safety and efficacy of netasrsudil 0.02% ophthalmic solution, a ROCK inhibitor and norepinephrine transporter inhibitor, in open-angle glaucoma and ocular hypertension.
These 2 studies were double-masked, randomized, non-inferiority clinical trials, Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2). These studies included 1167 patients randomized to receive netarsudil 0.02% qd, timolol bid, and netarsudil 0.02% bid (ROCKET-2 only) and described three-month results. Netasurdil treatment resulted in a clinically significant IOP reduction from baseline (P < 0.001) and was non-inferior to timolol in both trials where maximum baseline IOP was < 25 mmHg. Conjunctival hyperemia was the most frequent reported adverse event (incidence of 50-53% with netarsudil qd, 59% with netarsudil bid, and 8-10% with timolol bid), with conjunctival hemorrhage and cornea verticillata also reported frequently. Conjunctival hyperemia and hemorrhage were expected as ROCK inhibitors dilate the vasculature.1 As netarsudil bid resulted in a greater incidence of adverse events and higher patient discontinuation rate (30% vs 10-12% qd dosing), the authors suggest that the optimal dosing regimen is qd in the evening.
ROCK inhibitors are an effective new addition to glaucoma therapy. Their unique mechanism of increasing aqueous outflow through the trabecular pathway is mechanistically additive to our other available treatments.
References
- Rao PV, Pattabiraman PP, Kopczynski C. Role of the Rho GTPase/Rho kinase signalling pathway in pathogenesis and treatment of glaucoma: Bench to bedside research. Exp Eye Res. 2017;158:23-32.
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