Aerie Pharmaceuticals’ eye drug meets main goal in phase 3 trial

The study achieved its primary efficacy endpoint demonstrating statistical superiority over each of its components, including Aerie product candidate Rhopressa (netarsudil ophthalmic solution) 0.02%, and market leading prostaglandin analogue (PGA) latanoprost, all of which were dosed once daily in the evening.

The study evaluated patients with maximum baseline intraocular pressures (IOPs) ranging from above 20 to below 36 mmHg (millimeters of mercury).

The IOP-lowering effect of Roclatan was 1 to 3 mmHg greater than monotherapy with either latanoprost or RhopressaTM throughout the duration of the study. 

Roclatan Phase 3 Highlights for Mercury 1

Roclatan dosed once daily achieved the primary efficacy endpoint of demonstrating statistical superiority over both latanoprost and Rhopressa at the primary endpoint range of baseline IOPs from above 20 to below 36 mmHg for each of the nine measured time points.

IOPs were measured at 8 a.m., 10 a.m., and 4 p.m. at week 2, week 6, and day 90. Roclatan IOP lowering exceeded that of latanoprost in a range of 1.3 to 2.5 mmHg, and exceeded Rhopressa IOP lowering in a range of 1.8 to 3.0 mmHg. Efficacy levels were consistent across the 90-day period for all arms in the study.

Roclatan mean diurnal IOP-lowering exceeded that of latanoprost by an average across the study duration of 1.9 mmHg and exceeded Rhopressa by 2.6 mmHg.

Roclatan reduced mean diurnal IOPs to 16 mmHg or lower in 61 percent of patients, a significantly higher percentage than observed in the comparator arms.

The most common Roclatan adverse event was hyperemia, or eye redness, which was reported in approximately 50 percent of patients, or 30 percent above baseline, and was scored as mild for the large majority of these patients. There were no drug-related serious adverse events for any of the comparators in the trial.

Aerie will hold an "Investor Day" in New York City on October 5, 2016 to cover further details from the Mercury 1 trial and to provide a general business update.

Vicente Anido, Jr., Ph.D., Chairman and Chief Executive Officer at Aerie, said: "We are very pleased by these RoclatanTM 90-day efficacy results from the Mercury 1 clinical trial. As expected, the topline efficacy demonstrated in this trial clearly reconfirms the potential for RoclatanTM to become the most efficacious IOP-lowering therapy to enter the market, if approved.

"If Mercury 1 and 2 are successful, we expect to file the NDA for RoclatanTM near year-end 2017."

Dr. Anido continued, "We also noted that the RhopressaTM arm demonstrated high levels of efficacy across the full range of baseline IOPs studied, and the efficacy was maintained for the 90-day period. Importantly, RhopressaTM demonstrated comparable levels of IOP lowering to latanoprost at baseline IOPs ranging from 20 to 25 mmHg in Mercury 1. This performance for RhopressaTM is consistent with levels observed in the previous Phase 2b trials for RhopressaTM and RoclatanTM."

Richard A. Lewis, M.D., Aerie's Chief Medical Officer added, "Once-daily RoclatanTM has shown a degree of IOP lowering in Mercury 1 that is quite impressive, especially when considering its ability to bring patient pressures down to levels as low as 8 to 14 mmHg. The safety profile of RoclatanTM observed thus far in Mercury 1 points to a safe and tolerable product."

About Roclatan

Roclatan is a once-daily eye drop that combines Rhopressa, as described below, with latanoprost, a PGA that is the most widely prescribed glaucoma drug in the world.

Based on our preclinical studies and clinical trials, we believe that Roclatan, if approved, would be the first glaucoma product to lower IOP through all known mechanisms: (i) increasing fluid outflow through the trabecular meshwork, the eye's primary drain, (ii) increasing fluid outflow through the uveoscleral pathway, the eye's secondary drain, (iii) reducing fluid production in the eye, and (iv) reducing episcleral venous pressure (EVP).

By covering the full spectrum of known IOP-lowering mechanisms, Roclatan has the potential to provide a greater IOP-lowering effect than any currently approved glaucoma product.

The first Phase 3 registration trial for Roclatan, named Mercury 1 is a 12-month safety trial in 718 patients with a 90-day efficacy readout, which is the subject of this press release. The topline efficacy readout demonstrated that Roclatan was statistically superior to each of its components.

The second Phase 3 registration trial, named Mercury 2, is a 90-day efficacy trial that commenced in March 2016, and a third Phase 3 registration trial, named Mercury 3, is expected to commence in Europe in the first half of 2017. Mercury 3 is not necessary for approval in the U.S., but rather to facilitate regulatory approval and commercialization in Europe.

About Rhopressa

Rhopressa (netarsudil ophthalmic solution) 0.02%, is a novel eye drop that we believe, if approved, would become the only once-daily product available that, based on Aerie's preclinical studies, specifically targets the trabecular meshwork, the eye's primary fluid drain and the diseased tissue responsible for elevated IOP in glaucoma. Preclinical studies have also demonstrated that Rhopressa lowers episcleral venous pressure, which contributes approximately half of IOP in healthy subjects.

Further, based on Aerie's preclinical studies, Rhopressa provides an additional mechanism that reduces fluid production in the eye and therefore lowers IOP.

Biochemically, Rhopressa has been shown in Aerie studies to inhibit both Rho Kinase (ROCK) and norepinephrine transporter (NET). Recent preclinical studies have also shown that Rhopressa may have disease-modifying properties, including an anti-fibrotic effect on the trabecular meshwork and the potential to increase perfusion of the trabecular meshwork. Preclinical research is also currently underway to evaluate the potential neuroprotective benefits of Rhopressa.

The results of two Phase 3 registration trials (Rocket 2 and Rocket 1) for Rhopressa were included in a NDA filing submitted to the FDA in the third quarter of 2016. Rocket 2 represents the pivotal trial, and Rocket 1 is supportive.

There are two additional Phase 3 trials currently underway for Rhopressa, named Rocket 3 and Rocket 4. Rocket 3 is a 12-month safety-only study in Canada that is not needed for the NDA filing. Rocket 4 is designed to provide adequate six-month safety data for regulatory filing purposes in Europe, and is also not needed for the NDA filing.