The Academic Glaucoma Practice of New Jersey

Teaching: Dr Khouri serves as the director of resident education at the Institute of Ophthalmology & Visual Science. Dr Khouri is an active member of the American Academy of Ophthalmology and the World Glaucoma Association and chairs educational activities at national and international scientific meetings.  

Research: Together with a team of researchers Dr Khouri supervises innovative  glaucoma and telemedicine research with medical students and research associates. Ongoing research at Dr Khouri's Glaucoma Lab focuses on improving outcomes of treatments for glaucoma as well as studying new classes of medications, and novel drug delivery methods. Translational research in imaging aims at improving detection of glaucoma during ocular screening and tele-Glaucoma.

Once-daily netarsudil 0.02% vs twice-daily timolol maleate 0.5% in ocular hypertension or open-angle glaucoma, the ROCKET-4 study

Albert Khouri, MD, Newark, NJ
Jason Bacharach, MD, North Bay Eye Associates, Inc., Petaluma, CA, United States
Richard A. Lewis, MD, Sacramento Eye Consultants, Sacramento, CA, United States
Dale Usner, PhD
Puiwah Braswell, PMP, Aerie Pharmaceuticals, Inc., Irvine, CA, United States
Nancy Ramirez, MS, Bedminster, New Jersey
Casey Kopczynski, PhD, Aerie Pharmaceuticals, Durham, NC, United States
Theresa GH. Heah, MD, Aerie Pharmaceuticals, Bedminster, NJ, United States

Purpose/Relevance:

Netarsudil, a ROCK/NET inhibitor, lowers intraocular pressure (IOP) primarily by increasing trabecular outflow.1 In prior phase 3 trials, once-daily (QD) netarsudil 0.02% exhibited clinically significant IOP lowering in patients with elevated IOP.2 We summarize 6-month data from the phase 3 ROCKET-4 study.

Methods:

ROCKET-4 (NCT02558374) was a double-masked, randomized trial in patients with unmedicated IOP >20 and <30 mmHg at 8:00 AM and >17 and <30 mmHg at 10:00 AM and 4:00 PM administered QD (PM) netarsudil 0.02% or twice-daily (BID) timolol maleate 0.5% for 6 months. Mean IOP was measured at 8:00 AM, 10:00 AM, and 4:00 PM at week 2, week 6, and months 3–6. The primary efficacy endpoint 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 mmHg (per-protocol population). Adverse events (AEs) were recorded to month 6.

Results:

In total, 186 patients from each arm were included in the primary analysis at baseline. Mean baseline IOP in the primary efficacy population was similar between treatment arms. QD netarsudil met the primary endpoint of noninferiority to BID timolol at all time points up to month 3; mean diurnal IOP through month 3 was 16.8–17.2 mmHg for netarsudil and 16.9–17.1 mmHg for timolol. The IOP-lowering efficacy of QD netarsudil remained within the noninferiority range of BID timolol at all time points over months 4–6. Noninferiority was also seen in patients with baseline IOP <27 mmHg or <30 mmHg. The most frequent AE was conjunctival hyperemia, which was reported in 48% of netarsudil-treated patients and graded as mild in 77% of those affected. Other ocular AEs in ROCKET-4 were comparable to those reported in prior netarsudil trials.2 No treatment-related serious AE was reported for netarsudil. Significant reductions in mean heart rate of up to 3 bpm were seen for timolol (p<0.0001).

Discussion:

In ROCKET-4, QD netarsudil was noninferior to BID timolol in patients with baseline IOP <25 mmHg over 3 months (primary analysis). In this final analysis, netarsudil demonstrated a consistent level of IOP lowering across all baseline IOPs that was durable over 6 months.

Conclusion:

QD netarsudil has demonstrated consistent and sustained IOP lowering in 3 phase 3 trials, with tolerable ocular safety.