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- - 1-3 Netarsudil once daily in in daily once Netarsudil 1,2 Glaucoma specialists interviewed specialists Glaucoma FDA approval was based on data data on based was approval FDA the evening was comparable in in comparable was evening the daily twice 0.5% timolol to efficacy in trials clinical 2 and 1 Rocket in Hg mm 25 under IOP with patients IOP with patients in 4 Rocket in and Hg. mm 30 under eye once-daily the say article this for their to addition welcomed a is drop (MIGS) at New York Eye Surgery Eye York New at (MIGS) co- MD, Epstein, “David Center. and Pharmaceuticals Aerie of founder pioneer, clinician-scientist glaucoma a a develop to out set purposefully function the provide could that drug surgeon glaucoma every that ality natural eye’s the enhance to sought: tra the through functionality outflow be will legacy His meshwork. becular new this with success found he that inhibitor— ROCK mechanism—the of class novel first the represents that receive to medication IOP-lowering glau the reach and approval FDA years.” 20 in market coma random 4 and 2, 1, Rocket the from which trials, clinical controlled ized, in daily once netarsudil compared twice 0.5% timolol with evening the dem netarsudil 2, Rocket In daily. lowering IOP consistent onstrated IOPs all at and months across12 tested. - (ROCK/NET)

Rho kinase and and kinase Rho —and it has a unique mech unique a hasit —and “In many ways, Rhopressa is the is Rhopressa ways, many “In result of a glaucoma surgeon’s view of of view surgeon’sglaucoma a of result IOP-lowering ideal an be might what Radcliffe, M. Nathan said medication,” specializing surgeon glaucoma a MD, surgery glaucoma microinvasive in class of compounds— of class tranport norephinephrine inhibitors in results that (MOA) action of anism humor aqueous of outflow increased meshwork. trabecular the through 2018 - - MARCH

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coma management. Netarsudil management. coma 0.02% solution ophthalmic wo decades have passed have decades wo novel a of debut the since glau for agent IOP-lowering

Figure 1. Schematic of the anterior segment highlighting anatomy relevant to IOP homeostasis. Netarsudil ophthalmic Figure 1. Schematic of the anterior segment highlighting anatomy relevant to IOP homeostasis. Netarsudil ophthalmic solution 0.02%, the first FDA-approved agent in a new treatment class (ROCK inhibitors) for the reduction of IOP, is believed to improve trabecular meshwork outflow.

T elevated IOP in patients with open- with patients in IOP elevated hyperten ocular or glaucoma angle new a represents Netarsudil sion. (Rhopressa; Aerie Pharmaceuticals) Aerie (Rhopressa; topical the spell; dry that ended has approved was drop eye therapeutic lowering for 2017 late in FDA the by market since the 1990s. market WRITER BY ROCHELLE NATALONI, SENIOR STAFF PATIENTS AND PROVIDERS PROVIDERS AND PATIENTS medications to reach the glaucoma IOP-lowering class of first novel inhibitor, represents the Netarsudil, a ROCK/NET THERAPY INCREASES OPTIONS FOR FOR OPTIONS INCREASES THERAPY NEWLY APPROVED GLAUCOMA GLAUCOMA APPROVED NEWLY Images courtesy of Aerie Pharmaceuticals Aerie of courtesy Images CATARACT & REFRACTIVE SURGERY TODAY

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therapeutic armamentarium, and its profile suggests that it can be used effectively alone or with other medications to help patients reach and maintain their target pressures. Jason Bacharach, MD, director of research at North Bay Eye Associates in Sonoma, California, and faculty at California Pacific Medical Center, San Francisco, said availability of this new class of therapy should be a source of excitement for everyone who manages glaucoma. “Rho kinase inhibi- tors work very well as an adjunct to prostaglandins in low- ering IOP. In addition to use as a first-line agent in certain cases, their synergistic effect with prostaglandins will bode well for their initial use as an adjunct when IOP is affected by prostaglandins but more reduction is needed,” he said. Dr. Radcliffe noted the benefits of netarsudil’s potential use as an adjunctive agent. “In an era when the systemic safety profile of other twice-daily, single-agent adjunctive medications has become somewhat complex, Rhopressa will simplify things for eye care practitioners.” Figure 2. Netarsudil offered consistent IOP reduction, even in patients with a low The availability of this new treatment is particularly baseline IOP. timely, he said. “Today, glaucoma physicians are looking to restore natural flow through minimally invasive surgical our treatment armamentarium and that this new drug will techniques or through pharmacotherapy. Its unique mecha- assist in reducing the rate of visual disability and progression nism coupled with its novel medication class will likely make of glaucoma,” she said. Rhopressa an attractive therapeutic option in 2018.” Constance O. Okeke, MD, MSCE, an assistant professor Glaucoma specialist Janet B. Serle, MD, pointed out that of ophthalmology at Eastern Virginia Medical School in netarsudil’s benefits include having stable efficacy in eyes Norfolk, Virginia, said the availability of a new drug such with lower and higher baseline IOPs and that its approval as netarsudil will significantly affect how she manages expands treatment options for patients (Figure 2). Dr. Serle patients. “Even though we are in the midst of an explosion is a professor of ophthalmology and the glaucoma fellow- of surgical treatments for glaucoma, we still heavily use eye ships director at the Icahn School of Medicine at Mount drops. Eye drops will still be utilized for a long time because Sinai Hospital in New York. “Rhopressa, dosed once daily in they have been our go-to for treatment of glaucoma, so the evening, has efficacy comparable to the two most com- this new treatment can have a major impact.” monly prescribed first-line agents, and has mostly mild and Dr. Okeke went on to explain, “There are different sce- tolerable side effects. This profile makes it a first-line option narios that will come up with glaucoma patients, where for lowering IOP,” she said. they may not be amenable to having either laser treatment Because netarsudil acts at different receptors than other or surgery first. Some might prefer to try a medication, or currently available drugs, Dr. Serle said she expects that there are patients who are on various medications and it will be additive in efficacy to the other classes of IOP- have problems with tolerability, or there may be situations lowering compounds that act primarily by suppressing where we have tried laser treatment—or even surgery— aqueous humor formation. and we just need their IOP a few points lower, but the Additionally, the single-dose regimen may have an impact prospect moving on to a more invasive option does not on patient adherence. “The once-daily dosing regimen is appeal to the patient. All of these scenarios represent expected to enhance compliance and simplify patients’ daily instances where being able to consider a new drug that uti- routines,” Dr. Serle said. “Rhopressa will be beneficial for our lizes a different MOA could be beneficial.” patients with glaucoma as first-line therapy and as adjunc- Beyond that, she adds, it is exciting that netarsudil has tive therapy. This drug should also be considered for patients a profile that makes it synergistic with other medications. who have been intolerant to or have had inadequate efficacy “Whether it is used as a standalone or in conjunction with with other medications, patients who are poorly compliant other treatments, it will play a significant role in glaucoma. with two- and three-times daily dosing regimens, elderly Its regimen, simplicity, and tolerability for adherence is patients who need additional IOP reduction to avoid surgical huge. Its efficacy, synergy, and unique MOA for usage make intervention, and patients requiring additional IOP reduc- me extremely excited about using it.” tion to achieve stability of their disease. It is expected that Aerie Pharmaceutical’s other main IOP-lowering prod- many patients will benefit from the addition of Rhopressa to uct, Roclatan (netarsudil 0.02%/latanoprost 0.005%), is

MARCH 2018 | CATARACT & REFRACTIVE SURGERY TODAY 33 Assistant Professor of Ophthalmology, Eastern Assistant Professor of Ophthalmology, Eastern Glaucoma and cataract specialist, private practice, [email protected] Financial disclosure: Consultant (Novartis, Bausch New York Eye Surgery Center, New York Surgery Center, New York New York Eye Professor of Ophthalmology, Associate Clinical [email protected] (Aerie Financial disclosure: Consultant Glaucoma Professor of Ophthalmology, [email protected] Financial disclosure: Shareholder (Aerie Virginia Medical School, Norfolk, Virginia Virginia Eye Consultants, Norfolk & Lomb); Investigator (Aerie Pharmaceuticals) New York Eye and Ear Infirmary, New York New York Eye and Ear Infirmary, Bausch & Lomb, Pharmaceuticals, Allergan, Novartis, Shire) School of Medicine, Fellowships Director, Icahn New York, New York Pharmaceuticals); Consultant (Aerie Pharmaceuticals, Allergan, Auventx, Bausch & Lomb, Gedeon-Richter); Research Support (Allergan, Inotek, Ocular Therapeutix)        CONSTANCE O. OKEKE, MD, MSCE n n n n NATHAN M. RADCLIFFE, MD NATHAN M. RADCLIFFE, n n n n JANET B. SERLE, MD n n n - 2018;186:116-127. Am J Ophthalmol. Financial disclosure: Investigator and Consultant Financial disclosure: Investigator and Consultant Director of Research, North Bay Eye Associates, Director of Research, North Bay Eye Associates, Faculty member, Glaucoma Department, California [email protected] (Aerie Pharmaceuticals) (Aerie Pharmaceuticals) Sonoma, California Pacific Medical Center, San Francisco    n 4. Serle JB, Lewis RA, Kopczynski CC, Heah T. 3-month interim report of 4. Serle JB, Lewis RA, Kopczynski CC, Heah study of topical PG324 (fixed a prospective 12-month safety and efficacy combination of netarsudil 0.02% and latanoprost 0.005%) compared to the individual components in subjects with elevated intraocular pressure. Paper presented at: the Association for Research in Vision and Ophthalmology Annual Meeting; May 9, 2017; Baltimore. JASON BACHARACH, MD n n n 1. Serle JB, Katz LJ, McLaurin E, Heah T, Ramirez-Davis N, Usner DW, Novack E, Heah T, Ramirez-Davis N, Usner 1. Serle JB, Katz LJ, McLaurin Two phase the ROCKET-1 and ROCKET-2 Study Groups: GD, Kopczynski, CK for to timolol in pa the safety and efficacy of netarsudil 3 clinical trials comparing intraocular pressure. tients with elevated CC, Novack GD. AR-13324 2. Bacharach J, Heah T, Ramirez N, Kopczynski of two phase 3 clinical studies in ophthalmic solution 0.02%: topline results ocular hypertension. Paper resented patients with open angle glaucoma and March 3-6, 2016; Fort at: American Glaucoma Society Annual Meeting. Lauderdale, Florida. GD, and the ROCKET-4 3. Khouri AS, Heah T, Kopczynski CK, Novack parallel study of Netarsudil Investigator Group. A double-masked, randomized, to timolol maleate ophthalmic Ophthalmic Solution, 0.02% QD compared intraocular pressure (ROCKET-4). solution, 0.5% BID in patients with elevated in Vision and Ophthalmology Paper presented at: the Association for Research Annual Meeting; May 9, 2017, Baltimore. 2018 - - - - - MARCH

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4 According to Dr. Bacharach, netBacharach, Dr. to According lowered IOP better than each of itsof each than better IOP lowered statisticallya in components individual 1Mercury the in fashion significant trials,”clinical 3 phase 2 Mercury and explained. she taglandin analogues bodes well forwell bodes analogues taglandin couldwhich netarsudil/latanoprost, combina fixed-dose first the become Unitedthe in latanoprost with tion know “We added, Serle Dr. States. Rhopressathat studies Roclatan from Roclatan additive. are latanoprost and application (NDA) submission for for submission (NDA) application to expected is drug combination the of quarter second the in place take year. this arsudil’spros with synergy evident tion of netarsudil and latanoprost, latanoprost, and netarsudil of tion primary its achieved drop eye the 3 phase two in endpoint efficacy and 1 Mercury trials, registration suc achieved also and 2, Mercury efficacy and safety 12-month cessful 1. Mercury in results about a year behind netarsudil in in netarsudil behind year a about combina dose fixed A development. CATARACT & REFRACTIVE SURGERY TODAY

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