New Fixed-Dose, Once-Daily Combo Eyedrop Shows Efficacy in Glaucoma

Shuchi B. Patel, MD


September 10, 2019

The introduction of Rocklatan, a once-daily, fixed-dose combination of the rho kinase inhibitor netarsudil and the prostaglandin analogue latanoprost, has broadened the spectrum of medical management for patients with open-angle glaucoma or ocular hypertension.

Three-month data from the randomized, double-masked MERCURY 1 trial[1] provided compelling evidence to support its recent approval by the US Food and Drug Administration. This trial compared the safety and efficacy of this fixed-dose combination versus monotherapy with netarsudil or latanoprost alone in adult patients with either primary open-angle glaucoma or ocular hypertension. Patients were eligible for inclusion if the intraocular pressure (IOP) in both unmedicated eyes was > 20 mm Hg but < 36 mm Hg at 8 AM, and > 17 mm Hg but < 36 mm Hg at 10 AM and 4 PM. Those who were on ocular hypotensive medications had to undergo an appropriate washout period. Patients were excluded if they were on more than two ocular hypotensive medications. The primary endpoint was mean IOP at 8 AM, 10 AM, and 4 PM at week 2, week 6, and month 3.

The trial found that the fixed-dose combination drop reduced IOP 1.3-3.0 mm Hg more than either netarsudil or latanoprost alone. A statistically significantly higher proportion of patients achieved diurnal IOP < 15 mm Hg with the combination than with monotherapy. Overall, the combination met superiority criteria at all time points.

A Beneficial Combination

Though a relatively new treatment option, netarsudil has been shown to be noninferior to timolol.[2] It potentially lowers IOP through several mechanisms, including increasing trabecular outflow, decreasing aqueous production, and reducing episcleral venous pressure.[3,4,5,6,7] Because prostaglandin analogues reduce IOP through the separate mechanism of action of increasing uveoscleral outflow,[8] and also use once-daily dosing, they potentially make for an ideal pairing with netarsudil in a fixed-dose medication. It also stands to reason that a combination of netarsudil and latanoprost would reduce IOP more than either agent alone, as shown in the MERCURY 1 trial, and may even have a synergistic effect.

Many patients in my practice are already on multiple medical therapies, and I have been adding netarsudil in those who still need lower IOP. In my experience, adding netarsudil to not only latanoprost but also other medications has further reduced IOP. This is consistent with the theory that its very different mechanism of action to that of the currently available IOP-lowering agents makes it a complementary drug. The amount of IOP reduction also does not seem to be blunted by patients being on other drops. Further studies to show the effect of netarsudil in combination with beta-blockers, carbonic anhydrase inhibitors, and alpha-agonists would be useful.

Conjunctival hyperemia is the most common side effect noted in the trial, which I have observed. However, it has not been prohibitive in any of my patients, because it is not irritating, does not decrease vision, and is mostly cosmetic. Thus far, the only thing I have found to be prohibitive is the cost of the medication, although many patients still opt to continue it given the improvement in IOP.

This combination drug can significantly help to reduce IOP in patients with glaucoma—and its once-daily dosing will definitely improve compliance, which has been shown to occur when the drop burden is lowered.[9] I look forward to the final results of the MERCURY 1 trial, as well as future studies on the efficacy of netarsudil in combination with other medications for different types of glaucoma.

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