Rocket 4 researcher describes trial results comparing Rhopressa with timolol

The most common adverse event for Rhopressa was mild, transient conjunctival hyperemia.

The once-daily glaucoma eye drop Rhopressa was found to be comparable to twice-daily timolol in lowering IOP, according to 90-day results of Aerie Pharmaceuticals’ Rocket 4 phase 3 trial.

Three-month data from 214 patients using Rhopressa (netarsudil ophthalmic solution 0.02%) and 209 patients using timolol also revealed that Rhopressa met non-inferiority criteria when compared with timolol for prespecified baseline IOPs less than 27 mm Hg and less than 28 mm Hg.

“This also held true for baseline IOPs less than 29 mm Hg, but it was not prespecified,” principal investigator Jason Bacharach, MD, said.

For baseline IOPs below 30 mm Hg, Rhopressa was not quite as efficacious as timolol at two follow-up time points. “But the difference between the two drugs was only 0.03 mm Hg,” Bacharach said.

Jason Bacharach

The trial also showed no evidence of tachyphylaxis, which was checked at 2 weeks and 3 months.

If approved, Rhopressa would become the only once-daily product to specifically target the trabecular meshwork, according to Bacharach.

“Drops currently on the market either reduce aqueous production or they divert fluid to a secondary outflow mechanism,” he said.

Mechanisms of action

Besides increasing outflow through the trabecular meshwork, preclinical trials of Rhopressa demonstrated that the drug potentially lowers episcleral venous pressure and appears to reduce fluid production in the eye, similar to beta blockers.

Bacharach said the most commonly used drop for glaucoma is a once-daily prostaglandin, most notably the generic latanoprost.

“However, the goal of Rhopressa is not necessarily to compete with prostaglandins but to demonstrate its additivity to prostaglandins and the fact that it is a once-daily drop,” he said.

The most common adverse event for Rhopressa was conjunctival hyperemia, which was reported in about 16% of patients at each study visit but was scored as mild for 85% of those patients and overall was transient. “This finding is in line with prior studies,” Bacharach said.

There were no drug-related serious adverse events and no evidence of treatment-related systemic effects.

In addition, Rhopressa did not have any impact on heart rate.

The beta blocker timolol, on the other hand, reduced the mean heart rate by two to three beats per minute, even though patients in the timolol arm of the study were excluded if they had a history of hypersensitivity to the drug or any contraindication systemically.

But only 6.7% of timolol patients demonstrated hyperemia in the phase 3 safety profile, which is a compilation of the Rocket studies.

Other adverse events

Three other adverse events findings were conjunctival hemorrhage (sporadic subconjunctival petechiae): 11.7% for Rhopressa vs. 2% for timolol; cornea verticillata (asymptomatic non-toxic lipid despots with no visual function impact and only visible via biomicroscopy evaluation): 11.7% vs. 0%, respectively; and instillation site pain (transient for both arms): 23.4% vs. 24.9%, respectively.

“Systemically, Rhopressa is a safer drug than timolol, and Rhopressa is a very well-tolerated drug from a systemic standpoint,” Bacharach said. “Moreover, there were no serious adverse events seen in any of the Rhopressa clinical trials.”

Bacharach said that Rhopressa is “a well-researched drug with over 2,000 clinical patients on it. The drug demonstrates excellent once-daily efficacy in four phase 3 clinical trials, with stability through 1 year.”

Based on the study results to date, “it appears that Rhopressa will have excellent additivity to prostaglandin analogues in the future as an adjunctive agent,” Bacharach said.

Because of a third-party manufacturing facility’s lack of preparedness for FDA preapproval inspection, the new drug application for Rhopressa is scheduled to be refiled in January, for which the 90-day efficacy data from the Rocket 4 phase 3 study will be included.

If there are no hitches, Bacharach expects FDA approval of Rhopressa in the first quarter of 2018.

Meanwhile, phase 3 clinical trials are ongoing for a combination netarsudil/latanoprost agent, for which an NDA filing is expected near the end of 2017.

“Rhopressa will most likely be positioned, at least early on until the fixed combination [Roclatan] comes to market, as an excellent choice for a first-line adjunct to prostaglandin,” Bacharach said, adding that both Rhopressa and Roclatan would be administered once a day at bedtime. – by Bob Kronemyer

Disclosure: Bacharach reports he is a consultant and researcher for Aerie Pharmaceuticals.

The once-daily glaucoma eye drop Rhopressa was found to be comparable to twice-daily timolol in lowering IOP, according to 90-day results of Aerie Pharmaceuticals’ Rocket 4 phase 3 trial.

Three-month data from 214 patients using Rhopressa (netarsudil ophthalmic solution 0.02%) and 209 patients using timolol also revealed that Rhopressa met non-inferiority criteria when compared with timolol for prespecified baseline IOPs less than 27 mm Hg and less than 28 mm Hg.

“This also held true for baseline IOPs less than 29 mm Hg, but it was not prespecified,” principal investigator Jason Bacharach, MD, said.

For baseline IOPs below 30 mm Hg, Rhopressa was not quite as efficacious as timolol at two follow-up time points. “But the difference between the two drugs was only 0.03 mm Hg,” Bacharach said.

Jason Bacharach

The trial also showed no evidence of tachyphylaxis, which was checked at 2 weeks and 3 months.

If approved, Rhopressa would become the only once-daily product to specifically target the trabecular meshwork, according to Bacharach.

“Drops currently on the market either reduce aqueous production or they divert fluid to a secondary outflow mechanism,” he said.

Mechanisms of action

Besides increasing outflow through the trabecular meshwork, preclinical trials of Rhopressa demonstrated that the drug potentially lowers episcleral venous pressure and appears to reduce fluid production in the eye, similar to beta blockers.

Bacharach said the most commonly used drop for glaucoma is a once-daily prostaglandin, most notably the generic latanoprost.

“However, the goal of Rhopressa is not necessarily to compete with prostaglandins but to demonstrate its additivity to prostaglandins and the fact that it is a once-daily drop,” he said.

The most common adverse event for Rhopressa was conjunctival hyperemia, which was reported in about 16% of patients at each study visit but was scored as mild for 85% of those patients and overall was transient. “This finding is in line with prior studies,” Bacharach said.

There were no drug-related serious adverse events and no evidence of treatment-related systemic effects.

In addition, Rhopressa did not have any impact on heart rate.

The beta blocker timolol, on the other hand, reduced the mean heart rate by two to three beats per minute, even though patients in the timolol arm of the study were excluded if they had a history of hypersensitivity to the drug or any contraindication systemically.

But only 6.7% of timolol patients demonstrated hyperemia in the phase 3 safety profile, which is a compilation of the Rocket studies.

Other adverse events

Three other adverse events findings were conjunctival hemorrhage (sporadic subconjunctival petechiae): 11.7% for Rhopressa vs. 2% for timolol; cornea verticillata (asymptomatic non-toxic lipid despots with no visual function impact and only visible via biomicroscopy evaluation): 11.7% vs. 0%, respectively; and instillation site pain (transient for both arms): 23.4% vs. 24.9%, respectively.

“Systemically, Rhopressa is a safer drug than timolol, and Rhopressa is a very well-tolerated drug from a systemic standpoint,” Bacharach said. “Moreover, there were no serious adverse events seen in any of the Rhopressa clinical trials.”

Bacharach said that Rhopressa is “a well-researched drug with over 2,000 clinical patients on it. The drug demonstrates excellent once-daily efficacy in four phase 3 clinical trials, with stability through 1 year.”

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Based on the study results to date, “it appears that Rhopressa will have excellent additivity to prostaglandin analogues in the future as an adjunctive agent,” Bacharach said.

Because of a third-party manufacturing facility’s lack of preparedness for FDA preapproval inspection, the new drug application for Rhopressa is scheduled to be refiled in January, for which the 90-day efficacy data from the Rocket 4 phase 3 study will be included.

If there are no hitches, Bacharach expects FDA approval of Rhopressa in the first quarter of 2018.

Meanwhile, phase 3 clinical trials are ongoing for a combination netarsudil/latanoprost agent, for which an NDA filing is expected near the end of 2017.

“Rhopressa will most likely be positioned, at least early on until the fixed combination [Roclatan] comes to market, as an excellent choice for a first-line adjunct to prostaglandin,” Bacharach said, adding that both Rhopressa and Roclatan would be administered once a day at bedtime. – by Bob Kronemyer

Disclosure: Bacharach reports he is a consultant and researcher for Aerie Pharmaceuticals.