Pooled Efficacy and Safety Profile of Netarsudil Ophthalmic Solution 0.02% in Patients With Open-angle Glaucoma or Ocular Hypertension

Abstract

Precis: In pooled phase III analyses, once-daily netarsudil 0.02% resulted in intraocular pressure (IOP) reduction that was noninferior to twice-daily timolol 0.5%, with minimal treatment-related serious or systemic adverse events (AEs). Ocular AEs were generally tolerable.

Purpose: The purpose of this study was to assess the efficacy and safety of the Rho kinase inhibitor netarsudil in patients with open-angle glaucoma or ocular hypertension.

Patients and methods: Pooled analysis of data from the ROCKET-1 to 4 phase III studies of once-daily (PM) netarsudil or twice-daily timolol in patients with open-angle glaucoma or ocular hypertension. The primary efficacy measure was mean IOP at 8:00 AM, 10:00 AM, and 4:00 PM at week 2, week 6, and month 3 in patients with baseline IOP <25 mm Hg.

Results: In the pooled primary efficacy population (netarsudil, n=494; timolol, n=510), once-daily netarsudil was noninferior to twice-daily timolol at all 9 timepoints through month 3. Mean treated IOP ranged from 16.4 to 18.1 mm Hg among netarsudil-treated patients and 16.8 to 17.6 mm Hg among timolol-treated patients. In the pooled safety population (n=839 in each treatment group), treatment-related serious AEs occurred at similar frequencies in each treatment group (netarsudil, 0.1%; timolol, 0%). The most common ocular AE, conjunctival hyperemia (netarsudil, 54.4%; timolol, 10.4%), was graded as mild in 77.6% (354/456) of affected netarsudil-treated patients.

Conclusions: Once-daily netarsudil resulted in IOP lowering that was noninferior to twice-daily timolol, with tolerable ocular AEs that were generally mild and self-resolving. As a first-in-class agent in the United States, with a novel mechanism of action, netarsudil may provide a useful therapeutic option for patients who would benefit from IOP lowering.

FIGURE 1

Pooled analysis population. *Numbers of patients shown are the safety population. †A netarsudil bid study arm was included in ROCKET-2 and ROCKET-3 but was not evaluated in this analysis. AE indicates adverse event; bid, twice daily; IOP, intraocular pressure; OAG, open-angle glaucoma; OHT, ocular hypertension; QD, once daily.

FIGURE 2

Mean IOP through month 3 in the per-protocol population of patients with baseline IOP <25 mm Hg (primary efficacy population). Error bars are ±SD. CI indicates confidence interval; IOP, intraocular pressure; SD, standard deviation.

FIGURE 3

A, Change from baseline in mean diurnal intraocular pressure (IOP) at month 3 for subgroups with different baseline IOP thresholds (per-protocol population). B, Percentage of patients at month 3 achieving ≥20% reduction in mean diurnal IOP for subgroups with different baseline IOP thresholds (per-protocol populations). *P<0.05 (once-daily netarsudil 0.02% vs. twice-daily timolol 0.5%). Error bars are SEM. SEM indicates standard error of the mean.

FIGURE 4

Mean change from baseline in heart rate. *P<0.01 versus baseline. Error bars are ±SD. SD indicates standard deviation.

FIGURE 5

A, Mean conjunctival hyperemia score (8:00 am) via biomicroscopy. B, Investigator-assessed maximum severity of conjunctival hyperemia (8:00 am) among patients administered once-daily netarsudil. Biomicroscopic grading of conjunctival hyperemia was performed on a standardized, 4-point scale [0=none (normal; appears white with a small number of conjunctival blood vessels easily observed); 1=mild (prominent pinkish-red color of both the bulbar and palpebral conjunctiva); 2=moderate (bright, scarlet red color of the bulbar and palpebral conjunctiva); 3=severe (“beefy red” with petechiae; dark red bulbar and palpebral conjunctiva with evidence of subconjunctival hemorrhage)].