Aerie Pharmaceuticals Announces Positive Phase 3 Topline Results for Netarsudil Ophthalmic Solution 0.02% Clinical Trial in Japan

Aerie Pharmaceuticals reported positive topline results for the company’s phase 3 clinical trial in Japan evaluating netarsudil ophthalmic solution 0.02% versus ripasudil hydrochloride hydrate ophthalmic solution 0.4%. The results showed that netarsudil 0.02% once daily was superior to ripasudil 0.4% twice daily in lowering IOP at week 4 (P<0.0001), the primary endpoint for the study.

Both netarsudil 0.02% and ripasudil 0.4% are Rho kinase (ROCK) inhibitors. They are designed to treat open-angle glaucoma and elevated IOP by increasing outflow of aqueous humor through the trabecular outflow pathway.

The clinical trial was a single-masked comparison of netarsudil 0.02% dosed once daily versus ripasudil 0.4% dosed twice daily in 245 subjects for 4 weeks. The baseline mean diurnal IOP was 20.5 and 20.8 mmHg” in the netarsudil 0.02%, and ripasudil 0.4% arm, respectively. At 4 weeks, netarsudil 0.02% reduced mean diurnal IOP by 4.7 mmHg (22.6%) from baseline compared to 3.0 mmHg (14.3%) with ripasudil 0.4% (p<0.0001).

Netarsudil 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. Netarsudil 0.02% is known by the name Rhokiinsa in the European Union, where it is approved for the reduction of elevated IOP in adult patients with primary open-angle glaucoma or ocular hypertension.

“We are pleased to have successfully completed our first phase 3 clinical trial in Japan which further confirmed that netarsudil ophthalmic solution 0.02% achieves impressive IOP-lowering efficacy in a patient population with lower baseline pressures. We believe that the statistically superior IOP-lowering of netarsudil versus the comparator in our study may suggest a very bright future for our product in Japan, a market where the comparator product is the only rho-kinase inhibitor commercially available. The IOP-lowering with netarsudil was consistent with that seen in the previous phase 2 study conducted in Japan as well as in our ROCKET and MERCURY studies conducted in the United States for Rhopressa and Rocklatan, respectively. With its once-daily dosing and strong safety profile, we believe that netarsudil will fulfill an unmet need for these patients with lower baseline IOPs,” said Benjamin F. McGraw, III, Pharm.D., Interim Executive Chairman at Aerie.

“The findings also suggest that the IOP reduction may predict strong efficacy in normal or low-tension glaucoma patients,” said David A. Hollander, MD, MBA, Chief R&D Officer at Aerie. “These patients suffer damage to the optic nerve in spite of having IOPs in the normal range. Historically it has been challenging to achieve the IOP reductions needed to prevent vision loss in this patient population.”

Netarsudil Ophthalmic Solution Phase 3 Clinical Trial Highlights

• This randomized, multi-center, parallel-group phase 3 clinical trial was initiated in November 2020. The objective of the study was to evaluate the ocular hypotensive efficacy and safety of netarsudil 0.02% once daily compared to ripasudil 0.4% twice daily, over a 4-week period in patients with open angle glaucoma or ocular hypertension.

• The study was designed in accordance with the requirements of Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) to support the potential regulatory submission of netarsudil ophthalmic solution in Japan. The primary efficacy endpoint was mean diurnal IOP at 4 weeks.

• A total of 245 randomized subjects were included, with 122 subjects in the netarsudil 0.02% arm and 123 subjects in the ripasudil 0.4% arm. A total of 238 patients (97%) completed the study.

• The baseline mean diurnal IOP was 20.5 and 20.8 mmHg in the netarsudil 0.02% and ripasudil 0.4% arm, respectively.

• At week 4 (primary endpoint), the mean diurnal IOP was statistically significantly lower (16.0 mmHg) in the netarsudil 0.02% group compared to the ripasudil 0.4% group (17.7 mmHg, p<0.0001).

• Netarsudil 0.02% reduced mean diurnal IOP by 4.7 mmHg (22.6%) from baseline compared to 3.0 mmHg (14.3%) with ripasudil 0.4% (P<0.0001). Statistically significant IOP lowering with netarsudil was also observed at each of the study timepoints, 9 am, 11 am, and 4 pm at all study visits at weeks one, two and four (p<0.01).

• The medications were safe and well-tolerated. The most common treatment emergent adverse event was conjunctival hyperemia (54.9% of subjects with netarsudil 0.02% and 62.6% of subjects with ripasudil 0.4%). The majority of ocular adverse events were rated as mild.

Aerie and Santen Pharmaceutical announced an exclusive collaboration and license agreement for Rhopressa and Rocklatan (netarsudil and latanoprost ophthalmic solution 0.02%/0.0005%) in Japan and several other Asian countries in October 2020. As part of this agreement, Santen is responsible for all regulatory process and commercialization related to the products in the territories covered by the agreement; however, Aerie and Santen collaborated on this first phase 3 clinical trial for Rhopressain Japan, which they co-funded.