Disclosures: Bacharach reports he is a consultant to Aerie Pharmaceuticals and has served as an investigator in numerous pharmaceutical and device studies, including the ROCKET, MERCURY and M.O.S.T. studies.
November 03, 2020
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Real-world data show additive effects of netarsudil

Netarsudil can be substituted for a current medication or added to another treatment.

Disclosures: Bacharach reports he is a consultant to Aerie Pharmaceuticals and has served as an investigator in numerous pharmaceutical and device studies, including the ROCKET, MERCURY and M.O.S.T. studies.
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The addition of netarsudil as an adjunctive treatment yielded further IOP lowering in patients with glaucoma enrolled in a phase 4 study.

The prospective, multicenter, open-label study showed that patients in a real-world setting who were treated with the once-daily Rho kinase (ROCK) inhibitor Rhopressa (netarsudil, Aerie Pharmaceuticals) achieved 4.3 mm Hg to 4.5 mm Hg of additional IOP reduction whether it was added to prior prostaglandin analogue (PGA) monotherapy or prior multi-drug therapy.

Jason Bacharach
Jason Bacharach

The study, dubbed M.O.S.T. (Multi-center Open-label Study), treated 260 subjects with primary open-angle glaucoma or ocular hypertension who needed additional IOP lowering. The primary outcome was change in IOP from baseline at 12 weeks. Investigators had discretion to enroll patients with any level of IOP and any treatment regimen. Netarsudil could be substituted for a current medication or added to another treatment. In all, 161 patients received Rhopressa as adjunctive therapy, while 99 used it as monotherapy.

Real-world results

In the M.O.S.T. adjunctive therapy group, IOP reduction at 12 weeks was approximately 20% from baseline, whether netarsudil was a first, second, third or fourth addition to a PGA.

Several independent studies have reported similar results. A retrospective analysis of 275 eyes found that adding netarsudil lowered IOP significantly for those on one, two, three or four other medications, with the greatest reduction observed in the last group. A review of the charts of 92 patients on a mean of 3.9 ± 0.1 medications revealed a mean IOP reduction of 2.2 ± 0.5 mm Hg (P < .0001) approximately 50 days after the addition of netarsudil. A third analysis including 172 eyes showed a mean decrease in IOP of 3.67 ± 4.91 mm Hg at 1 month (P < .001) with no statistically significant difference between patients on three or more or less than three medications at the same timepoint. A fourth analysis found that adding netarsudil to a standard four medication maximum medical therapy had a significantly greater IOP reduction (–21%) compared with patients who were switched from a PGA to latanoprostene bunod (–3%). The addition of netarsudil also resulted in a greater decline in IOP (–21%) than the addition of a fourth medication class (–10%).

Mechanism of action

The ability to lower IOP in a broad range of scenarios is likely a class effect. Reports exist of a similar phenomenon with the only other ROCK inhibitor, twice-daily Glanatec (ripasudil, Kowa). ROCK inhibitors act directly on the trabecular meshwork, increasing conventional outflow through Schlemm’s canal by relaxing the trabecular meshwork and reducing episcleral venous pressure (EVP).

EVP slows down aqueous drainage, adding to IOP, especially in eyes with lower baseline pressures. By lowering EVP, netarsudil effectively “lowers the floor,” allowing further IOP reduction even for those still progressing despite IOP in the mid to upper teens.

Adverse events and tolerability

Across the M.O.S.T. population, there were no treatment-related serious adverse events. The most common adverse event was conjunctival hyperemia, which occurred in 20.8% of subjects. The nature and frequency of adverse events in the independent real-world studies align with these results.

The results of these studies demonstrate how Rhopressa works in a real-world setting and closely reflect what I have experienced in my own clinical practice. The ability to significantly reduce IOP with good tolerability suggests that Rhopressa has an important adjunctive role to play for any patient who needs additional IOP reduction, regardless of current therapy.