ROCKET-4: IOP-lowering effect of netarsudil noninferior to timolol
Once-daily dosing of the Rho kinase (ROCK) inhibitor netarsudil is not inferior to twice-daily timolol in terms of lowering intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension, while having tolerable adverse events (AEs), according to the results of the phase III ROCKET-4 trial.
“As a new class of treatment with a novel mechanism of action, netarsudil QD has the potential to be used both as a single agent and as an adjunct to currently used IOP-lowering treatments,” the investigators said.
In ROCKET-4, 708 patients (mean age, 64 years; 62.85 percent female) with unmedicated early morning IOP of >20 to <30 mm Hg at baseline were randomized to receive netarsudil 0.02% QD (administered in the afternoon; n=351) or timolol 0.5% BID (n=357) for 6 months. A total of 243 and 314 patients completed treatment with the respective ophthalmic solution, with 186 patients from each treatment arm included in the efficacy analysis.
The primary endpoint of mean IOP at 0800, 1000 and 1600 hours at week 2, week 6 and month 3 ranged from 16.3–17.9 mm Hg in the netarsudil arm and 16.7–17.6 mm Hg in the timolol arm. Netarsudil QD fulfilled the noninferiority criteria. [Am J Ophthalmol 2019;doi:10.1016/j.ajo.2019.03.002]
Of note, the IOP-lowering effect of the ROCK inhibitor was consistent in patients with baseline IOP of <27 and <30 mm Hg and maintained over 6 months of treatment.
AEs occurred with greater frequency in the netarsudil vs timolol arm (80.1 percent vs 60.2 percent), but majority of AEs in the former were mild and considered manageable. The most commonly reported ocular AE with netarsudil was conjunctival hyperaemia (47.9 percent). No treatment-related serious AEs were reported in either treatment arm.
“The primary efficacy outcome in ROCKET-4 is consistent with the results of the two large phase III ROCKET-1 and ROCKET-2 studies, where the IOP-lowering effects of netarsudil QD met the criteria for noninferiority to timolol BID in patients with baseline IOP <25 mm Hg over 3 months,” the investigators pointed out. [Am J Ophthalmol 2018;186:116-127]
“However, unlike ROCKET-1 and ROCKET-2, ROCKET-4 demonstrated noninferiority of netarsudil QD to timolol BID when the analysis population included patients with maximum baseline IOP <27 mm Hg and also <30 mm Hg,” they added.
Currently, IOP is the only modifiable risk factor for disease progression in glaucoma or ocular hypertension. Elevation of IOP occurs due to abnormally high resistance to trabecular outflow. [Curr Opin Ophthalmol 2012;23:135-143]
Netarsudil ophthalmic solution 0.02% is a topically administered ROCK inhibitor approved by the US Food and Drug Administration in 2017. The drug increases trabecular outflow by reducing acto-myosin–driven cellular contraction and production of extracellular matrix proteins, as well as decreasing episcleral venous pressure. [J Ocul Pharmacol Ther 2018;34:380-386; J Ocul Pharmacol Ther 2018;4:40-51]