We are a publicly traded (NASDAQ: AERI), ophthalmic pharmaceutical company focused on the discovery, development and commercialization of first-in-class therapies for the treatment of patients with open-angle glaucoma and other diseases of the eye.
Glaucoma is one of the largest segments in the global ophthalmic market. In 2016, branded and generic glaucoma product sales exceeded $5.0 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.
Our first product, Rhopressa® (netarsudil ophthalmic solution) 0.02%, was approved by the United States Food & Drug Administration (FDA) in December 2017 for the lowering of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. Our second product, Roclatan™ (netarsudil/latanoprost ophthalmic solution) 0.02%/0.005%, is a fixed dose combination of Rhopressa® and latanoprost, a widely prescribed prostaglandin analogue (PGA). We expect to file our NDA for Roclatan™ in the second quarter of 2018. If approved, we believe Roclatan™ has the potential to be the most efficacious therapy for lowering of elevated IOP in the marketplace.
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 was 36 million, or 60 million monthly units, in 2016 and is expected to grow, driven in large part by the aging population.
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.
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 24 mmHg, 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 resubmitted the NDA for Rhopressa® ophthalmic solution on February 28, 2017 using the Rocket 2 results as pivotal and Rocket 1 as supportive. In May 2017, we received notification from the FDA that the FDA has completed its initial 60-day review of the Rhopressa® NDA and determined that the application is sufficiently complete to permit a substantive review. The Prescription Drug User Fee Act (PDUFA) goal date for the completion of the FDA’s review of the Rhopressa® NDA is set for February 28, 2018.
Discussed further in this website, Aerie reported in September 2016 the topline 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 topline 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 with baseline IOPs ranging from above 20 mmHg to below 25 mmHg, and based on final data also achieved non-inferiority to timolol for patients with baseline IOPs ranging from above 20 mmHg to below 30 mmHg. Rocket 4 was 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 were not necessary for the NDA filing in the U.S., Aerie filed this data to the NDA as supportive on February 28, 2017. Rocket 3 was a safety-only Phase 3 trial being conducted in Canada which was originally designed to supplement the twelve-month safety data from Rocket 2 and for which we have discontinued enrollment.
In a 24-hour, 12-patient pilot study comparing Rhopressa® efficacy to that of placebo, Rhopressa® demonstrated similar levels of IOP lowering during nocturnal and diurnal periods. This is potentially a further differentiating feature of Rhopressa® when considering that currently marketed products have demonstrated little or no efficacy at night and eye pressure is typically highest when patients are asleep.
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 completed our second Roclatan™ ophthalmic solution Phase 3 registration trial in May 2017, 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. The study achieved its primary efficacy endpoint demonstrating statistical superiority over each of its components, including Rhopressa®, and market-leading PGA, latanoprost. The study evaluated patients with maximum baseline IOPs ranging from above 20 to below 36 mmHg at nine measured time points over the trial. The IOP-lowering effect of Roclatan™ exceeded that of monotherapy with latanoprost in a range of 1.5 to 2.4 mmHg with efficacy levels remaining consistent for all arms in the study throughout the trial.
We commenced our Mercury 3 trial for European approval in mid-2017. Mercury 3 is designed to compare Roclatan™ to Ganfort®, a fixed-dose combination product of bimatoprost and timolol marketed in Europe, which if successful, is expected to improve our commercialization prospects in that region. 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.
We also recently commenced our Phase 1 and Phase 2 clinical trials designed to ultimately obtain regulatory approval for Rhopressa® in Japan.
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, its ability to lower IOP consistently over a 24-hour period, and also 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® ophthalmic 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.
We are also evaluating in preclinical studies AR-13503, an Aerie-owned small molecule that inhibits both Rho kinase and protein kinase C. AR-13503 has demonstrated significant reduction in lesion size associated with wet age-related macular degeneration (AMD) and diabetic macular edema (DME) in animal models. In addition, our preclinical retina franchise also includes AR-1105, a dexamethasone steroid with the potential to treat DME. Further, we are exploring drug delivery opportunities using a bio-erodible polymer sourced from DSM that may provide sustained release of small molecule product candidates such as AR-13503 to the retina. We also have exclusive rights to PRINT® technology for ophthalmic indications, thus providing a manufacturing platform for precisely-sized implants.
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 plan to commercialize ourselves 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.
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- 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.