Eyeworld

EW GLAUCOMA 74 May 2017 by Tony Realini, MD, MPH, EyeWorld Contributing Writer visits, with differences ranging from 1.5–2.4 mm Hg, he said. A responder analysis demon- strated that some patients had remarkable responses to the fixed combination. "Overall, 65% of sub- jects in the fixed combination group had a 30% or greater IOP reduction, 46% had a 35% or greater IOP reduc- tion, and 35% had a 40% or greater IOP reduction," he described. "A 40% IOP reduction with one drop dosed one time per day, we have not previously seen." Dr. Asrani ascribed the substan- tial additivity of latanoprost and netarsudil to their complementary mechanisms of action. Prostaglan- dins lower IOP primarily by increas- ing aqueous outflow through the uveoscleral pathway. In contrast, netarsudil potentially lowers IOP through three distinct mechanisms: relaxing trabecular smooth muscle and decreasing episcleral venous pressure, both of which promote increased aqueous outflow, as well as reduction in aqueous production through the molecule's norepineph- rine transport inhibitor activity. Practical applications Both drugs remain in development, and their place in the stepped treatment paradigm for glauco- ma management will not be fully known until they become available for widespread use. Access will also shape their role in clinical practice— it remains unclear how valuable third-party payors will view the attributes of these products and how expensive they will be for both insured and uninsured patients with glaucoma. EW Editors' note: Dr. Brandt has financial interests with ForSight VISION5 (Par- sippany-Troy Hills, New Jersey). Dr. Bu- denz has financial interests with Alcon (Fort Worth, Texas), ForSight VISION5, Inotek (Lexington, Massachusetts), and Ivantis (Irvine, California). Dr. Asrani has no financial interests related to this article. Contact information Asrani: sanjay.asrani@duke.edu Brandt: jdbrandt@ucdavis.edu Budenz: Donald_budenz@med.unc.edu Although 6 mm Hg may seem less than what might be expected from prostaglandin therapy, Dr. Brandt points out that in some patient populations, the efficacy trade-off may be worthwhile in exchange for the adherence benefit. "This device may be of value for the growing population of patients with early disease who can't, won't, or don't take their medications as prescribed," he said. Netarsudil/latanoprost fixed combination The rho kinase inhibitor netarsudil mesylate may have encountered some obstacles in its Phase 3 de- velopment as a single agent, but in combination with latanoprost, this drug could become a valuable tool in the management of OAG. Sanjay Asrani, MD, Duke University, Durham, North Carolina, presented the 3-month interim data from an ongoing 12-month study of the netarsudil/latanoprost fixed combination versus each of its two constituents. "Mean IOP in the fixed com- bination group was lower than latanoprost at all nine timepoints," he said, referring to the 8 a.m., 10 a.m. and 4 p.m. timepoints at visits 2, 6, and 12 weeks after initiating therapy. Mean diurnal IOP (the aver- age of the 8 a.m., 10 a.m., and 4 p.m. time points) with the fixed combination was lower than with latanoprost at all three on-treatment A recent Phase 2 clinical trial compared the IOP-lowering efficacy of the bimatoprost ring to twice-dai- ly timolol 0.5% in 130 subjects with ocular hypertension or open-an- gle glaucoma (OAG). The study's primary endpoint was at 3 months, and most patients then entered an open-label extension study with follow-up through as long as 19 months. Through cycles of up to 6 and 7 months of continuous wear with a single device, "IOP reductions of up to 6 mm Hg were observed, which is clinically significant," Dr. Brandt said. Once placed, the device tends to remain in place throughout the intended 6-month dosing cycle. In the active period of the Phase 2 trial, retention was as high as 93% to 99% in patients not using any other drops—and thus not manipulating their eyelids to instill eye drops—he explained. Importantly, "There we no cases where subjects were unaware of device loss," he said. This may be due to the nature of the device itself. "The ring is white, and the nasal as- pect of the ring can be visible in the medial canthal region," Dr. Brandt said. Other than this minor cosmetic issue, the device is otherwise well tolerated. "The most common treat- ment-emergent adverse events were mucus in 18% of eyes and punctate keratitis in 16%," Dr. Brandt said. Hyperemia (12%) and tearing (9%) were also seen, he added. New opportunities for individualized care A fter 2 decades of stag- nation, the glaucoma pharmaceutical world is poised to receive several novel therapies. Topical prostaglandin therapy has been the mainstay of first-line treatment since the turn of the century. New drugs with innovative mechanisms of action and sustained release formulations with extended dosing periods may challenge this long- time paradigm. At the recent annual meeting of the American Glaucoma Society in Coronado, California, several glaucoma specialists shared new data that may help identify the optimal use of these emerging products. Bimatoprost conjunctival ring "We have excellent meds to lower IOP," said Donald Budenz, MD, MPH, University of North Carolina, Chapel Hill, "but at least 60% of our patients have adherence problems, and we cannot tell which of our patients are nonadherent." Many patients require multiple medications to adequately control IOP, which makes the problem of adherence even worse. "With more than one bottle, adherence goes down precipitously," he added. These observations have driven substantial interest in the develop- ment of sustained release systems that would provide drug dosing over an extended period of time and reduce or eliminate the need for patients to self-dose on a daily basis. One such system, the bimatoprost conjunctival ring, may address the unmet need for such an option. The device consists of a poly- propylene core coated with bimato- prost-impregnated silicone. It is designed to elute bimatoprost in steady-state fashion over time. The ring itself measures 24 to 29 mm in diameter and is meant to rest in the superior and inferior fornices. The device is inserted by a clinician in the examination room. "It seats itself and is safe and well tolerated," said James Brandt, MD, University of California, Davis. "It is designed to be replaced by a clini- cian every 6 months." Novel glaucoma therapies Presentation spotlight Bimatoprost ocular insert being placed in the upper lid Source: John Sheppard, MD

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