Aerie Pharmaceuticals reported positive topline results for the company’s phase 2 clinical trial evaluating netarsudil ophthalmic solution in Japanese patients. Netarsudil is a Rho kinase (ROCK) inhibitor specifically designed to increase outflow of aqueous humor through the trabecular meshwork, the eye’s primary drainage pathway. Netarsudil ophthalmic solution 0.02% is known by the name Rhopressa in the United States and is approved for the reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension. It is also under regulatory review in the European Union, where it is called Rhokiinsa.
Netarsudil Ophthalmic Solution Phase 2 Highlights
- The objective of the 28-day phase 2 study was to evaluate the IOP-reducing effect and safety of three concentrations of netarsudil ophthalmic solution (0.01%, 0.02% and 0.04%) compared to placebo in subjects with open-angle glaucoma or ocular hypertension. All treatments were administered once daily in the evening.
- The study was designed in accordance with the requirements of Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) as a precursor to phase 3 trials to support potential regulatory submission of netarsudil ophthalmic solution in Japan. The primary efficacy endpoint was mean diurnal IOP on Day 29.
- The baseline IOPs tested in the study ranged from 15 to less than 35 millimeters of mercury (mmHg) for patients with open-angle glaucoma, and from 22 to less than 35 mmHg for patients with ocular hypertension. Previous studies have shown that the average IOP, as observed in Japan, is approximately 3 mmHg lower than as observed in the United States.
- A total of 215 randomized subjects were included, with between 51 and 55 subjects in each arm. Average baseline IOPs ranged from 20.3 mmHg to 21.1 mmHg across the four arms. A total of 207 patients completed the study.
- Mean diurnal IOP at Day 29 was statistically significantly lower in subjects treated with each of the netarsudil concentrations than those treated with placebo, with all P values <0.0001.
- The netarsudil ophthalmic solution 0.01% concentration reduced mean diurnal IOP by a range of 4.1 to 4.6 mmHg, the 0.02% concentration reduced mean diurnal IOP by a range of 4.4 to 4.8 mmHg, and the 0.04% concentration reduced mean diurnal IOP by a range of 4.8 to 5.1 mmHg. The placebo arm reduced mean diurnal IOP by a range of 1.4 to 1.7 mmHg. The ranges reflect IOP measurements taken at week 1, week 2 and week 4. IOP lowering was consistent across the measurement period.
- The most common adverse event was conjunctival hyperemia, which when measured by biomicroscopy, was observed in 23.6 percent of subjects in the netarsudil 0.01% arm, 37.0 percent of subjects in the netarsudil 0.02% arm, 56.9 percent of subjects in the netarsudil 0.04% arm, and 1.8 percent in the placebo arm. The level of conjunctival hyperemia observed in the netarsudil 0.02% arm was notably less than levels observed in the clinical trials for Rhopressa previously conducted in the United States. The large majority of the conjunctival hyperemia was considered mild. There were no serious adverse events.
- These topline results will be discussed in greater detail on Aerie’s third-quarter financial results call scheduled for November 6, 2019 at 5 p.m. ET, and a corresponding slide presentation will be made available at http://investors.aeriepharma.com approximately one hour before the call.
“The topline results of this large phase 2 study confirm that netarsudil ophthalmic solution maintains strong IOP-lowering efficacy in a patient population with lower baseline pressures, a clinical need that remains unmet by currently available glaucoma therapeutics in Japan, the United States and in Europe,” Vicente Anido, Jr., PhD, Chairman and Chief Executive Officer at Aerie, said in a company news release. “These findings, which will be presented in full at an upcoming ophthalmic congress, also suggest that the concentration of netarsudil that provides the best balance of efficacy and tolerability in this population is 0.02%, which is the concentration for Rhopressa currently marketed in the United States. We will now look to meet with Japan’s Pharmaceutical and Medical Devices Agency to discuss these results and identify next steps for a phase 3 program in Japan. With this data in hand we are advancing a number of different activities, including potential partnering discussions, to gain approval and ultimately commercialize our products in Japan.”