Our Product Portfolio


The following table summarizes each of our existing product candidates, their mechanisms of action, or MOAs, and their development status, as well as our intellectual property rights for these product candidates.

Product Candidate and Mechanism

Phase of Development

Intellectual
Property Rights

Rhopressa™

Triple-action 1 , 2 - ROCK/NET inhibition

Phase 3 registration trials commenced in July, 2014

Wholly-Owned

Roclatan™

Quadruple-action 1 , 2 , 3 - Combination of triple-action Rhopressa™ and latanoprost, a PGA

Phase 2b clinical trial completed June 2014
Phase 3 registrations trials expected to begin mid-2015

Wholly-Owned

AR-13533

Second-generation ROCK/NET inhibitor

Preclinical

Wholly-Owned


Rhopressa™

Triple-action Rhopressa™ 1 , 2 is a once-daily eye drop that inhibits Rho Kinase, or ROCK, and the norepinephrine transporter, or NET, which are both novel biochemical targets for lowering of intraocular pressure, or IOP. By inhibiting these targets, we believe Rhopressa™ reduces IOP via three separate MOAs: (i) through ROCK inhibition, it increases fluid outflow through the trabecular meshwork, or TM, which accounts for approximately 80% of fluid drainage from the eye; (ii) as demonstrated in a recent preclinical study, it reduces episcleral venous pressure, or EVP, which represents the pressure of the blood in the episcleral veins of the eye where eye fluid drains into the bloodstream; and (iii) through NET inhibition, it reduces the production of eye fluid. 1 , 2 The Roclatan™ Phase 2b clinical trial that recently completed in June 2014 included Rhopressa™ as one of the comparators. In this study, the Rhopressa™ arm had a similar outcome to that seen in the prior Phase 2b clinical trial.

We believe that triple-action Rhopressa™ 1 , 2 has several significant differentiating characteristics that would make it a strong competitor in both the prostaglandin analogue, or PGA, and non-PGA market segments, if approved, including:

  • IOP-Lowering Effect - In our Phase 2b clinical trial, once-daily Rhopressa™ demonstrated mean IOP reductions of 5.7 and 6.2 mmHg (millimeters of mercury) on days 28 and 14, respectively. Studies have shown that a sustained 5 mmHg reduction in IOP reduces risk of disease progression by approximately 50%.4

  • Consistent IOP-Lowering Effect Across Various Baseline IOPs - Published studies have indicated that currently marketed PGA and non-PGA products do not lower IOP as effectively in patients with low to moderately elevated baseline IOPs relative to patients with higher baseline IOPs.5 In our Phase 2b clinical trial, Rhopressa™ reduced IOP at consistent levels across all baseline IOPs tested in the trial. The results of a preclinical in vivo study sponsored by Aerie and reported in February 2014 suggest that this differentiated effect may be attributable to the ability of Rhopressa™ to lower EVP.

  • Triple-Action MOA 1 , 2 - We believe Rhopressa™ works through three MOAs: increasing outflow through the TM, decreasing fluid production in the eye and reducing EVP. If approved, we believe Rhopressa™ would be the only once-daily drug available that works through these three MOAs. In addition, we believe the three MOAs of Rhopressa™ are highly complementary to the MOA of market-leading PGAs, which increase fluid outflow through the uveoscleral pathway.

  • Once-Daily Dosing - The most commonly prescribed non-PGA drugs are dosed two to three times daily, which places a considerable daily burden on patients, who are generally required to use these drugs for the remainder of their lives. Rhopressa™ is being developed as a once-daily dosed glaucoma therapy. This more convenient dosing regimen is expected to result in higher patient compliance, which may lead to improved outcomes.6

  • Safety Profile - In our Phase 2a and Phase 2b clinical trials for Rhopressa™, a total of 209 patients were exposed to Rhopressa™. The most common adverse event for Rhopressa™ was hyperemia, which is a cosmetic asymptomatic redness of the eye. When present, the hyperemia was scored as "mild" the majority of the time when evaluated by the eye-care professionals in the morning following instillation of the drop the previous night. Hyperemia is a common safety finding also associated with PGAs.

  • Absence of Systemic Side Effects8 - Rhopressa™ has demonstrated an absence of systemic side effects in Phase 1 and 2a/b clinical trials to date, including our Phase 1 pharmacokinetic study, the results of which were reported in January 2014.

In addition, Rhopressa™ targets the TM, the diseased tissue responsible for elevated IOP in glaucoma and the eye's primary drain, whereas commonly prescribed PGAs and non-PGAs target the secondary drain and/or the fluid production in the eye, respectively.

Pending successful advancement of the Phase 3 registration studies, three-month efficacy results are expected in the middle of the second-quarter 2015 for Rocket 1 and mid-2015 for Rocket 2. If the trials are successful, the Company expects to submit a New Drug Application filing by mid-2016.


Roclatan™

Quadruple-action Roclatan™ 1 , 2 , 3 , a single-drop fixed-dose combination of Rhopressa™ and latanoprost, lowers IOP through the same three MOAs as Rhopressa™ 1 , 2 and, as a fourth MOA3, through the ability of latanoprost to increase fluid outflow through the uveoscleral pathway, the eye's secondary drain. We believe Roclatan™, if approved, would be the only glaucoma product to cover the full spectrum of currently known IOP-lowering MOAs. Therefore, we believe Roclatan™ could compete in both the PGA and non-PGA markets.

We believe that quadruple-action Roclatan™ 1 , 2 , 3 has several significant differentiating characteristics that would make it a strong competitor in the glaucoma market, if approved, including:

  • Efficacy Superior to Latanoprost - In our recently completed Phase 2b clinical trial, Roclatan™ achieved its primary efficacy endpoint of statistically significant superiority over each of its components on day 29. The trial included 297 patients with non-medicated entry IOPs that ranged from 22 to 36 mmHg. Roclatan™ lowered mean diurnal IOP from 25.1 mmHg at baseline to 16.5 mmHg on day 29, a 34 percent decrease in IOP. Roclatan™ mean diurnal IOP reduction was approximately 2 mmHg greater than the IOP reduction with latanoprost.

  • Quadruple-Action MOA 1 , 2 , 3 - We believe Roclatan™, if approved, would be the only glaucoma product that covers the full spectrum of currently known IOP-lowering MOAs.

  • Once-Daily Dosing - The most commonly prescribed non-PGA drugs are dosed two to three times daily, which places a considerable daily burden on patients, who are generally required to use these drugs for the remainder of their lives. Roclatan™ is being developed as a once-daily dosed glaucoma therapy. This more convenient dosing regimen is expected to result in higher patient compliance, which may lead to improved outcomes.6

  • Safety Profile - The most common adverse event for Roclatan™ was hyperemia, which is a cosmetic asymptomatic redness of the eye. When present, the hyperemia was scored as "mild" the majority of the time when evaluated by the eye-care professionals in the morning following instillation of the drop the previous night. Hyperemia is a common safety finding also associated with non-PGA glaucoma drugs.7

  • Absence of Systemic Side Effects8 - Consistent with the safety profiles of its individual components, Rhopressa™ and latanoprost, Roclatan™ demonstrated an absence of systemic side effects in its Phase 2b clinical trial.


AR-13533

In addition to our primary product candidates, Rhopressa™ and Roclatan™, we are in the preclinical development stage with AR-13533, our second-generation ROCK/NET inhibitor. AR-13533 does not require enzymatic conversion in the eye to deliver maximal ROCK inhibitor activity, and therefore AR-13533 may provide additional IOP-lowering effect in patients beyond that obtained with Rhopressa™. We have not submitted an investigational new drug application, or IND, for AR-13533 to the FDA and there can be no assurance that an IND will be submitted.

 

References

  1. 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.
  2. Kiel JW, Kopczynski C. Effect of AR-13324 on episcleral venous pressure (EVP) in Dutch Belted rabbits. ARVO 2014. Abstract 2900.
  3. Xalatan® Package Insert Revised November 2014.
  4. Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M, for the EMGT Group. Reduction of Intraocular Pressure and Glaucoma Progression. Results from the Early Manifest Glaucoma Trial. Arch Ophthalmol 2002. 120:1268-1279.
  5. Hedman K, Alm A. A pooled-data analysis of three randomized, double-masked, six-month clinical studies comparing the intraocular pressure reducing effect of latanoprost and timolol. Eur J Ophthalmol 2000. 10:95-104.
  6. Schwartz GF, Quigley HA. Adherence and Persistence with Glaucoma Therapy. Survey Ophthalmol. 2008. 53(1):S57-S68.
  7. Bacharach J, Levy B, Ramirez N, Kopczynski CC, Novack GD for the PG324-CS201 Study Group. Evaluation of PG-324, a fixed dose combination of AR-13324 and latanoprost, in patients with elevated intraocular pressure in a double-masked, randomized, controlled study. American Glaucoma Society 2015 (in press).
  8. Data on File