麻豆传媒

CHICAGO -- The Rho kinase inhibitor netarsudil (Rhopressa) demonstrated noninferiority to timolol ophthalmic solution for control of intraocular pressure (IOP), meeting the primary endpoint of a phase III randomized trial.

Treatment with netarsudil led to a mean diurnal IOP at 3 months of about 17.15 mmHg compared with 16.93 mmHg with timolol. A safety expansion study showed a consistency of treatment effect in both groups to month 6 and no significant differences between treatment groups.

Netarsudil and timolol had similar effects on IOP in patients with baseline IOP of >20 to <25 mmHg, >20 to <27 mmHg, and >20 to <30 mmHg, reported Jason Bacharach, MD, of North Bay Eye Associates in Petaluma, California, here at the American Academy of Optometry meeting. The most common adverse effect of netarsudil was conjunctival hyperemia, which was generally mild and transient.

"At month 6, netarsudil was noninferior to timolol in the primary and secondary efficacy analyses," Bachrach said. "The pressure-lowering efficacy was maintained over the entire 6-month timeframe. Netarsudil had no evidence of treatment-related serious or systemic effects with a tolerable ocular adverse event profile."

The efficacy of netarsudil has been demonstrated in five clinical trials, involving a total of 3,000 patients, he added. The trials include the ROCKET series, comparing netarsudil and timolol, and the MERCURY studies evaluating the fixed-dose combination of netarsudil and latanoprost (Roclatan) versus treatment with the individual drugs.

Unlike currently available therapies to lower IOP, netarsudil appears to decrease episcleral venous pressure in addition to its primary IOP-lowering mechanism of increased trabecular meshwork outflow.

"It is the only category of ophthalmic pharmaceuticals to treat glaucoma that we know of that doesn't have a degradation in its effect according to the starting intraocular pressure," said Bacharach. "For all classes of medicine, if you look at the FDA studies that led to their approval, including prostaglandins, for every millimeter starting pressure, there is about a half millimeter less effect of that class of medicine, and that's probably because of episcleral venous pressure."

Asked whether he would consider using netarsudil as initial therapy for lowering IOP, Bacharach referred to the trials of the fix-dose combination, showing an additive effect of netarsudil to a latanoprost. He said adjunctive use is the most likely niche for the drug at this point, noting that the drug had a favorable review from an on Friday. If approved, netarsudil would be the first new glaucoma medication in 20 years.

Nonetheless, Bacharach would not rule out the possibility of a role for netarsudil as initial therapy for selected patients.

"It's really easy to lower someone's pressure from 30 to 20, but it's really hard to lower pressure from 20 to 14, or even lower," he said. "There might be some specific benefit to this drug as a primary therapy in people with normal-tension glaucoma, but that's purely speculative. It hasn't been studied yet."

Bacharach reported findings from the , which involved 700 patients with baseline untreated IOP >20 mmHg but <30 mmHg at 8 a.m. and >17 mmHg but <30 mmHg at 10 a.m and 4 p.m. Patients were randomized to netarsudil once daily or timolol twice daily.

The primary endpoint was the composite IOP from three measurements obtained at 2 weeks, 6 weeks, and 3 months (a total of nine IOP measurements) among patients who had a baseline IOP >20 but <25 mmHg. Noninferiority was defined as IOP within 1.5 mmHg of timolol at all time points and within 1.0 mmHg at a majority of time points (at least five of nine). Secondary outcomes analyses of patients with baseline IOP >20 but <27 mmHg and with baseline IOP >20 but <30 mmHg.

The results demonstrated noninferiority of netarsudil versus timolol for the primary and secondary endpoints and at months 4, 5, and 6.

Consistent with prior studies of netarsudil, the most common adverse events were conjunctival hyperemia (48%), corneal verticillata (13%), and conjunctival hemorrhaging (<10%). Conjunctival hyperemia was mild in three-fourths of cases and transient, as no more than 10% of patients had hyperemia at any time during the trial. Verticillata caused no vision problems and was reversible with drug discontinuation. Hemorrhaging was sporadic and petechial in nature, often requiring a microscope to see clearly, said Bacharach.

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