Netarsudil/Latanoprost Fixed-Dose Combination for Elevated Intraocular Pressure: Three-Month Data from a Randomized Phase 3 Trial

Abstract

PURPOSE: To compare the ocular hypotensive efficacy and safety of a fixed-dose combination (FDC) of the Rho kinase inhibitor netarsudil and latanoprost vs monotherapy with netarsudil or latanoprost. DESIGN: Three-month primary endpoint analysis of a randomized, double-masked, phase 3 clinical trial. METHODS: Adults with open-angle glaucoma or ocular hypertension (unmedicated intraocular pressure [IOP] >20 and <36 mm Hg at 8:00 AM) were randomized to receive once-daily netarsudil/latanoprost FDC, netarsudil 0.02%, or latanoprost 0.005% for up to 12 months. 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. RESULTS: Mean treated IOP ranged from 14.8-16.2 mm Hg for netarsudil/latanoprost FDC, 17.2-19.0 mm Hg for netarsudil, and 16.7-17.8 mm Hg for latanoprost. Netarsudil/latanoprost FDC met the criteria for superiority to each active component at all 9 time points (all P < .0001), lowering IOP by an additional 1.8-3.0 mm Hg vs netarsudil and an additional 1.3-2.5 mm Hg vs latanoprost. At month 3, the proportion of patients achieving mean diurnal IOP £15 mm Hg was 43.5% for netarsudil/ latanoprost FDC, 22.7% for netarsudil, and 24.7% for latanoprost. No treatment-related serious adverse events were reported; treatment-related systemic adverse events were minimal. The most frequent ocular adverse event was conjunctival hyperemia (netarsudil/latanoprost FDC, 53.4%; netarsudil, 41.0%; latanoprost, 14.0%), which led to treatment discontinuation in 7.1% (netarsudil/lata-noprost FDC), 4.9% (netarsudil), and 0% (latanoprost) of patients. CONCLUSIONS: Once-daily netarsudil/latanoprost FDC demonstrated IOP reductions that were statistically and clinically superior to netarsudil and latanoprost across all 9 time points through month 3, with acceptable ocular safety.

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

“…In addition to the individual MER-CURY-1 and -2 study results, this pooled analysis further supports the hypothesis that combining two IOP-lowering agents with distinct mechanisms of action can reduce IOP with greater efficacy than either agent alone. Analysis of pooled safety data indicated that these results were also consistent with those of the individual MERCURY studies up to 12 months [1][2][3]. Netarsudil/latanoprost FDC was associated with no treatment-related serious AEs, minimal systemic AEs, and tolerable ocular AEs.…”

“…This pooled analysis of phase 3 MERCURY-1 and MERCURY-2 pivotal studies was limited by the design differences between the two studies [1,3]. MERCURY-1 was a 3-month study for efficacy endpoints and a 12-month study for safety endpoints whereas MERCURY-2 was a 3-month study for efficacy and safety endpoints.…”

“…Two phase 3 studies, MERCURY-1 and MER-CURY-2, were conducted to investigate efficacy and safety of a once-daily, fixed-dose combination formulation (FDC) of netarsudil and latanoprost (ROCKLATAN Ò ) for treatment of patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) [1][2][3]. These studies demonstrated that the netarsudil/latanoprost FDC produced statistically and clinically relevant reductions from baseline in intraocular pressure (IOP) that exceeded the reductions provided by either agent alone.…”

“…The studies were conducted in accordance with IRB regulations and Good Clinical Practice Guidelines and adhered to the tenets included in the Declaration of Helsinki. The MERCURY-1 study was conducted in the USA for 12 months [1]. The MERCURY-2 study was conducted in the USA and Canada for 3 months [3].…”

Medikamentöse Therapie des Glaukoms

“…Sowohl das Mono-als auch das Kombinationspräparat werden jeweils 1 × täglich appliziert. In Studien konnte gezeigt werden, dass die Kombinationstherapie einen stärkeren drucksenkenden Effekt hatte als die Monotherapie der beiden Einzelsubstanzen [26]. Außerdem konnte in 3 verschiedenen Phase-III-Studien gezeigt werden, dass die drucksenkende Wirkung von Netarsudil 0,02 % 1 × täglich der von Timolol 0,5 % 2 × täglich in der Therapie von unbehandelten Patienten mit einem Ausgangsdruck von unter 25 mmHg nicht unterlegen ist [27].…”