Fixed-Dose Combination of Netarsudil and Latanoprost in Ocular Hypertension and Open-Angle Glaucoma: Pooled Efficacy/Safety Analysis of Phase 3 MERCURY-1 and-2

Introduction New open-angle glaucoma (OAG) and ocular hypertension (OHT) therapies that reduce treatment burden and improve outcomes relative to currently available agents are needed. Netarsudil, a novel Rho kinase inhibitor approved by the US Food and Drug Administration, reduces intraocular pressure (IOP) by increasing trabecular outflow. Two phase 3 superiority studies compared a fixed-dose combination (FDC) of netarsudil and the prostaglandin latanoprost with each active component for IOP-lowering efficacy. Methods Pooled efficacy and safety data were analyzed from MERCURY-1 and -2 studies in patients with OAG or OHT. Patients instilled one drop of netarsudil (0.02%)/latanoprost (0.005%) FDC (n = 483), netarsudil (0.02%, n = 499), or latanoprost (0.005%, n = 486) into each eye once-daily between 20:00 and 22:00. IOP was measured at 08:00, 10:00, and 16:00 at weeks 2, 6, and the primary endpoint at month 3. Results Baseline mean diurnal IOP was 23.6, 23.6, and 23.5 mmHg in netarsudil/latanoprost FDC, netarsudil, and latanoprost groups, respectively. Mean diurnal IOP in each group was 15.3, 18.1, and 17.5 mmHg at week 2, 15.7, 18.4, and 17.4 mmHg at week 6, and 15.8, 18.4, and 17.3 mmHg at week 12. The netarsudil/latanoprost FDC met criteria for superiority compared with each active component (p < 0.0001 for all nine time points). At month 3, among patients randomized to netarsudil/latanoprost FDC or latanoprost, 58.4% vs 37.3% (p < 0.0001) achieved IOP <= 16 mmHg. Among patients randomized to netarsudil/latanoprost FDC or netarsudil or latanoprost, 30.9% vs 5.9% (p < 0.0001) vs 8.5% (p < 0.0001) achieved at least a 40% reduction from baseline in mean diurnal IOP. Pooled safety results were consistent with individual MERCURY studies. Conclusion Once-daily netarsudil/latanoprost FDC produced statistically significant and clinically relevant reductions in mean IOP that were statistically superior to IOP reductions achieved by netarsudil and latanoprost monotherapy. Results of the pooled efficacy and safety analyses were consistent with the individual studies. Plain Language Summary In patients with open-angle glaucoma (OAG) or ocular hypertension (OHT), treatment to lower intraocular pressure (IOP) is needed to prevent optic nerve damage and vision loss. Many patients do not achieve sufficient IOP lowering with a single drug. The use of multiple IOP-lowering agents, which may have different dose regimens, can be complex and reduce patient adherence. Combination treatments that incorporate multiple agents are available, but until recently none included a prostaglandin analogue, the most widely prescribed first-line therapy. A once-daily, fixed-dose combination (FDC) therapy (ROCKLATAN(R)) has been approved in the USA that contains the prostaglandin analogue latanoprost and netarsudil, a novel Rho kinase inhibitor. The netarsudil/latanoprost FDC demonstrated efficacy and safety in lowering IOP among patients with OAG and OHT in the 12-month MERCURY-1 and the 3-month MERCURY-2 clinical trials. To better characterize efficacy and safety, we pooled and analyzed the data from each trial. The pooled data support the findings of the individual studies: Efficacy: 1. Netarsudil/latanoprost FDC demonstrated statistical superiority to the individual components netarsudil and latanoprost in decreasing IOP at all time points assessed over 3 months. 2. Nearly twice as many patients receiving FDC achieved at least a 30% reduction from baseline in IOP, as recommended by the American Academy of Ophthalmology for a first-line treatment, compared to the IOP reduction achieved by netarsudil and latanoprost monotherapy. Safety: No new safety signals were identified. Netarsudil/latanoprost FDC was associated with no treatment-related serious adverse events, minimal systemic adverse events, and manageable ocular adverse events.