Sustained benefit found with fixed-drug combination netarsudil/latanoprost


Results from MERCURY-1, a 12-month phase III pivotal trial, show that once daily treatment with fixed-dose combination netarsudil 0.02%/latanoprost 0.005% (Aerie Pharmaceuticals) is safe and provided significantly greater IOP-lowering than either of its components throughout follow-up.

By Cheryl Guttman Krader; Reviewed by Jacob Brubaker, MD

Results from MERCURY-1, a 12-month phase III pivotal trial, show that once daily treatment with fixed-dose combination (FDC) netarsudil 0.02%/latanoprost 0.005% (Aerie Pharmaceuticals) is safe and provided significantly greater intraocular pressure (IOP)-lowering than either of its components throughout follow-up.

“Many patients cannot achieve their target IOP using a single topical medication, but a polypharmacy regimen reduces medication adherence that in turn can compromise eye health outcomes,” said Jacob Brubaker, MD, a MERCURY-1 study investigator and in private practice, Sacramento Eye Consultants, Sacramento, CA. “FDC products can simplify the treatment regimen, but those that are available in the United States require dosing two or three times daily, and none contain a prostaglandin analog.”

Dr. Brubaker pointed out that the efficacy and safety data from this phase III study are consistent with those of MERCURY-2, the second phase III study.

“Collectively, their data suggest that the FDC netarsudil/latanoprost may address an unmet need for an FDC that provides greater efficacy than the prostaglandin analogs with a reduced treatment burden compared with current options,” he added.



MERCURY-1 data

MERCURY-1 was multicenter, double-masked studies randomizing 718 patients 1:1:1 to FDC netarsudil/latanoprost, netarsudil 0.02% (Rhopressa, Aerie Pharmaceuticals), or latanoprost 0.005%. All medications were applied as a single drop once daily in the evening.

Eligible patients had bilateral open-angle glaucoma or ocular hypertension and an unmedicated IOP after washout of existing IOP-lowering medications of >20 mm Hg to <36 mm Hg at 8 a.m. during 2 qualification visits and >17 mm Hg to <36 mm Hg at 10 a.m. and 4 p.m. at the second qualification visit. The 3 treatment groups were well-balanced for their baseline demographic characteristics.

Patients returned for follow-up at weeks 2 and 6 and months 3, 6, 9, and 12. The primary efficacy endpoint was mean IOP at 8 a.m., 10 a.m., and 4 p.m. at week 2, week 6, and month 3, and the primary safety endpoint was adverse events during the 12-month study.

MERCURY-1 was designed as a superiority trial and it met its primary efficacy endpoint with FDC netarsudil/latanoprost demonstrating significantly greater IOP-lowering than both of its components at week 2, week 6, and month 3.  Compared with both control groups and across all 3 timepoints, the treatment difference favoring the FDC group ranged from 1 mm Hg to 3 mm Hg.



Greater IOL lowering

The IOP-lowering effect of FDC netarsudil/latanoprost was also greater than with either netarsudil or latanoprost at the month 6, 9, and 12 follow-up visits. In addition, an efficacy analysis of the proportion of patients with a mean month 12 diurnal IOP ≤14 mm Hg, ≤15 mm Hg, ≤16 mm Hg, ≤17 mm Hg, and ≤18 mm Hg consistently found a statistically significant difference favoring the FDC group versus the 2 control groups.

At month 12, 82% of patients in the FDC netarsudil/latanoprost group compared with 57% of patients using netarsudil alone and 66% of latanoprost-treated patients had a mean diurnal IOP ≤18 mm Hg, Dr. Brubaker reported.

“Netarsudil is a novel product that is only recently available to our patients as a stand-alone agent,” Dr. Brubaker said. “The fixed-dose combination product would improve compliance with once-a-day dosing and was shown to be remarkably effective. With regards to the data and efficacy, I’m most excited by the proportion of patients who achieved a quite low IOP using the combination product.”



Common adverse event

The safety review showed that conjunctival hyperemia was the most common adverse event in all 3 study groups, but it occurred more often in patients using FDC netarsudil/latanoprost than in the netarsudil and latanoprost groups (63.0% versus 51.4% and 21.9%).

“In most patients who developed conjunctival hyperemia, it was graded as mild and occurred intermittently,” said Dr. Brubaker. “Its severity did not increase with ongoing treatment. By month 12, conjunctival hyperemia caused 7.6% of patients randomized to FDC netarsudil/latanoprost and 8.2% of those randomized to netarsudil to discontinue their treatment,”

Instillation site pain was the second most common adverse event in the FDC netarsudil/latanoprost and netarsudil groups (23.1% and 24.7% vs. 7.6% for latanoprost) followed by cornea verticillata (17.6% and 13.6% vs. 0%) and conjunctival hemorrhage (13.0% and 18.1% vs. 1.3%). Cornea verticillata was the cause of treatment discontinuation for 1.7% of netarsudil/latanoprost patients and 1.2% of netarsudil patients.

Jacob Brubaker, MD


This article is based on a poster presented by Dr. Brubaker at the 2018 American Glaucoma Society meeting. Dr. Brubaker is a consultant to and receives research grant funding from Aerie Pharmaceuticals.

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