We are a publicly traded (NASDAQ: AERI), clinical-stage pharmaceutical company focused on the discovery, development and commercialization of first-in-class therapies for the treatment of patients with glaucoma and other diseases of the eye.
Glaucoma is one of the largest segments in the global ophthalmic market. In 2015, branded and generic glaucoma product sales exceeded $4.7 billion in the United States, Europe and Japan in aggregate, according to IMS. Glaucoma is a progressive disease in which elevated levels of intraocular pressure, or IOP, are associated with damage to the optic nerve, resulting in irreversible vision loss and potentially blindness. Additionally, glaucoma is a highly individualized disease and there is no direct correlation of the level of IOP at diagnosis with damage to the optic nerve.
According to the National Eye Institute, it is estimated that over 2.7 million people in the United States suffer from glaucoma, a number that is expected to reach 4.3 million by 2030. Furthermore, The Eye Diseases Prevalence Research Group has estimated that only half of the nation’s glaucoma sufferers know that they have the disease. Prescription volume for glaucoma products in the United States alone exceeded 34 million in 2015 and is expected to grow, driven in large part by the aging population.
If approved, we believe our innovative product candidates could be effective across the majority of glaucoma patients. They are once-daily, well-tolerated eye drops that are designed to provide eye-care professionals with the first novel intraocular pressure-lowering mechanisms of action, or MOAs, to treat patients with glaucoma or ocular hypertension in over 20 years.
Our lead product candidate, Rhopressa™1 2 3 (netarsudil ophthalmic solution) 0.02%, successfully completed its second Phase 3 registration trial in September 2015. This trial, named Rocket 2, achieved its primary endpoint of non-inferiority of Rhopressa™ ophthalmic solution to comparator timolol across a range of baseline IOPs from above 20 millimeters of mercury (mmHg) to below 25 mmHg. In addition to successfully achieving non-inferiority to timolol at this endpoint range, the topline 12-month safety data from Rocket 2 confirmed a positive safety profile for the drug and demonstrated a consistent IOP lowering effect throughout the 12-month period at the specified timepoint.
Rhopressa™ ophthalmic solution also achieved non-inferiority to timolol in its first Phase 3 trial, named Rocket 1, at the pre-specified secondary endpoint range of baseline IOPs from above 20 mmHg to below 24mmHg, while not achieving non-inferiority to timolol at the primary endpoint range of below 27 mmHg due to performance at the top millimeter of the range. We expect to resubmit the NDA for Rhopressa™ ophthalmic solution near the end of Q1-2017 upon notification from our finished product contract manufacturer of their readiness for pre-approval inspection by the FDA using the Rocket 2 results as pivotal and Rocket 1 as supportive.
Discussed further in this website, Aerie reported in September 2016 the top line 90-day efficacy readout for its second product, Roclatan™ (netarsudil/latanoprost ophthalmic solution) 0.02%/0.005% in the Mercury 1 Phase 3 registration trial. In that trial Rhopressa™ ophthalmic solution demonstrated consistent efficacy across a broad spectrum of baseline IOPs and also demonstrated non-inferiority to market leading latanoprost at baseline IOPs ranging from over 20 mmHg to below 25 mmHg.
Further, successful top line 90-day efficacy data released in October 2016 for another Rhopressa™ ophthalmic solution Phase 3 clinical trial, named Rocket 4, Rhopressa™ ophthalmic solution demonstrated non-inferiority to timolol at the primary endpoint range from over 20 mmHg to below 25 mmHg, as well as from the pre-specified range of above 20 mmHg to below 28 mmHg. Rocket 4 is a six-month clinical trial designed to provide adequate safety data for regulatory filing in Europe. While the positive Rhopressa™ ophthalmic solution clinical data from Mercury 1 and Rocket 4 are not necessary for the NDA filing in the U.S., Aerie expects to file this data to the NDA as supportive. Rocket 3 is a safety-only Phase 3 trial being conducted in Canada which was originally designed to supplement the twelve-month safety data from Rocket 2.
Based on our clinical data and recent preclinical studies, we believe Rhopressa™ ophthalmic solution has several unique positive attributes, including a potential synergistic effect with market leading prostaglandin analogues (PGAs), and potential disease modification and neuroprotective features. We plan to further explore these as our developmental processes continue.
In September 2016 we completed the 90-day efficacy portion of the first Phase 3 registration trial for Roclatan™1 2 4 (netarsudil/latanoprost ophthalmic solution) 0.02%/0.005%, a fixed-dose combination of Rhopressa™ ophthalmic solution and the PGA latanoprost, which is approved for the lowering of IOP in patients with glaucoma. In this registration trial, named Mercury 1, Roclatan™ ophthalmic solution met all of its clinical endpoints, including statistically superior efficacy over each of its components and demonstrated better IOP lowering than latanoprost in a range of 1.3 to 2.5 mmHg. We commenced our second Roclatan™ ophthalmic solution Phase 3 registration trial in March 2016, named Mercury 2, designed to evaluate Roclatan™ ophthalmic solution for superiority to each of its components, Rhopressa™ ophthalmic solution and latanoprost in a 90-day efficacy trial. We expect to commence our Mercury 3 trial for European approval in 1H-2017. Based on its Phase 2b and Phase 3 registration trial performance, we believe Roclatan™ ophthalmic solution has the potential to be the most efficacious therapy in the market for patients with glaucoma or ocular hypertension.
In addition to our primary product candidates, Rhopressa™ ophthalmic solution and Roclatan™ ophthalmic solution, we are also exploring the longer-term impact of Rhopressa™ ophthalmic solution on the diseased trabecular meshwork, as well as neuroprotection, and evaluating possible uses of our existing proprietary portfolio of Rho kinase inhibitors beyond glaucoma. We have issued several research updates on preclinical results demonstrating the potential for Rhopressa™ pphthalmic solution to have disease-modifying activity in glaucoma patients by stopping and potentially reversing fibrosis in the trabecular meshwork, and also increasing perfusion in the trabecular outflow pathway thus increasing both drainage and the delivery of nutrients to the diseased tissue. Our research has also shown the potential of Rhopressa™ ophthalmic solution to promote retinal ganglion cell survival and axon regeneration.
We are also evaluating in preclinical studies AR-13154, an Aerie-owned small molecule that demonstrated significant reduction in lesion size associated with wet age-related macular degeneration (AMD) in animal models. Further, we are exploring drug delivery opportunities for both front and back of the eye, as well as potential additions to our ophthalmic product pipeline.
We own the worldwide rights for our current product candidates and retain the right to seek approval for all indications for these products. We currently plan to commercialize our products ourselves in North America. Regarding our international commercialization strategy, if our product candidates are successful, we may potentially commercialize ourselves or with a partner in Europe, and likely with a partner in Japan. Our intellectual property portfolio contains patents and pending patent applications related to composition of matter, pharmaceutical compositions and methods of use for our product candidates. We have patent protection for our primary product candidates, Rhopressa™ ophthalmic solution and Roclatan™ ophthalmic solution, in the United States through at least 2030.
- Wang RF, Williamson JE, Kopczynski C, Serle JB. Effect of 0.04% AR-13324, a ROCK, and norepinephrine transporter inhibitor, on aqueous humor dynamics in normotensive monkey eyes. J Glaucoma 2015. 24(1):51-4.
- Kiel JW, Kopczynski C. Effect of AR-13324 on Episcleral Venous Pressure (EVP) in Dutch Belted Rabbits. J Ocul Pharmacol Ther 2015; 31(3):146-151.
- Sturdivant JM,* Royalty SR, Lin CW, Moore LA, Yingling JD, Laethem CL, Sherman B, Heintzelman GR, Kopczynski CC, deLong M. Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma. Bioorg Med Chem Lett. 2016; 26:2475–2480.
- Xalatan® Package Insert Revised November 2014.