Aerie Pharmaceuticals announced the commencement of patient dosing in its phase 2 clinical trial designed in accordance with the requirements of Japan’s PMDA (Pharmaceuticals and Medical Devices Agency) to support potential regulatory submission of netarsudil ophthalmic solution in Japan. 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.
This phase 2 trial is being conducted in Japan as a precursor to phase 3 registration trials in that country. The prospective, double-masked, multicenter, placebo-controlled, parallel group study is designed to evaluate the IOP-reducing effect and safety of three concentrations of netarsudil ophthalmic solution over a 28-day period. Entry criteria include unmedicated baseline IOP ranges at 9 am of 15 mmHg to less than 35 mmHg for patients with open-angle glaucoma, and 22 mmHg to less than 35 mmHg for patients with ocular hypertension. A total of approximately 208 patients will be randomized equally across four treatment arms: netarsudil ophthalmic solution 0.01%, netarsudil ophthalmic solution 0.02%, netarsudil ophthalmic solution 0.04%, and placebo, all administered once daily in the evening.
As agreed with the PMDA, the design of this trial is consistent with that of a recent phase 2 pilot study conducted in a Japanese-American population in the United States, with the addition of the netarsudil ophthalmic solution 0.01% treatment arm to confirm the concentration of netarsudil most suitable for this population. Studies of glaucoma in Japan suggest that patients have baseline IOP that is generally lower than those experienced by patients in the United States and Europe, hence the IOP range in the netarsudil Japanese phase 2 trials begins lower, at 15 mmHg.
“Building upon the positive topline results of our pilot phase 2 study, we are very pleased to take this next step on the pathway toward a regulatory filing in Japan for netarsudil ophthalmic solution,” Vicente Anido, Jr., PhD, Chairman and Chief Executive Officer at Aerie, said in a company news release. “We anticipate completing enrollment in this study before the end of 2019 and then preparing for a netarsudil phase 3 program. We believe there continues to be substantial unmet need for novel glaucoma therapeutics in Japan, particularly medicines that are effective in patients with low baseline intraocular pressures.”
Topline results of the phase 2 pilot study in Japanese Americans were announced in January 2019. In that study, netarsudil ophthalmic solution 0.02% reduced mean diurnal IOP by a range of 5.0 to 5.3 mmHg in patients with an average baseline IOP of 18.3 mmHg. Netarsudil ophthalmic solution 0.04% reduced mean diurnal IOP by a range of 5.2 to 6.6 mmHg in patients with average baseline IOP of 20.2 mmHg. Both netarsudil arms produced significantly greater IOP reduction than placebo at Day 28. The safety findings were consistent with previous netarsudil trials.