Eyeworld

EW GLAUCOMA 48 July 2018 Pharmaceutical focus by Maxine Lipner EyeWorld Senior Contributing Writer latanoprostene was well tolerated with a low discontinuation rate." The second drug, netarsudil, is part of a new class that targets the trabecular outflow pathway, rho kinase inhibitors, Dr. Bacharach not- ed. Rho kinase increases contraction in smooth muscle-like cells such as those in the trabecular meshwork. This medication improves outflow by relaxing contracted trabecular meshwork tissue, he explained. 6 Dr. Serle pointed out that in ad- dition to increasing outflow through the trabecular pathway, netarsudil reduces episcleral venous pressure. Also, because netarsudil is a nor- epinephrine transporter inhibitor, it has a third potential mechanism, decreasing aqueous humor forma- tion. 7 Four Phase 3 clinical trials of ne- tarsudil have been completed. The Rocket 1, 2, 3, and 4 trials, which compared netarsudil dosed once daily in the evening with timolol dosed twice daily, showed that the IOP lowering of these drugs was comparable, Dr. Serle reported. "IOP reductions with netarsudil were sta- ble through 12 months of dosing," she said. 8 A fixed combination of ne- tarsudil 0.02% and latanoprost 0.005%, known as Roclatan (Aerie Pharmaceuticals), was submitted to the U.S. FDA for approval in May 2018. "This fixed dose combination was compared with the individual components in two Phase 3 clinical trials, Mercury 1, a 12-month study, and Mercury 2, a 3-month study," Dr. Serle said. "In Mercury 1 and 2, IOP reductions were 1 to 3 mm Hg greater with the fixed-dose combi- nation of netarsudil and latanoprost than with the individual compo- nents at all measurements." 9 Dr. Serle views these findings as confirming the additivity of netar- sudil and latanoprost and bolster- ing the consistent efficacy that the fixed-dose combination maintained through 12 months. "Additionally, in patients with baseline IOP below 25 mm Hg, netarsudil IOP lowering remained constant and similar to latanoprost through month 12," Dr. Serle said. that restricts outflow," Dr. Bacha- rach said, adding that the nitric oxide component targets and relaxes the trabecular meshwork tissue. He stressed the fact that there may be a need for nitric oxide here, which is bolstered by evidence that reduced levels of this have been found in glaucoma patients' eyes. 2 Dr. Serle pointed out that the latanoprostene bunod administered once a day has been shown in clini- cal trials to be slightly more effective than timolol 0.5% given twice daily. "In these trials, IOP reductions were 1 to 2 mm Hg greater with latano- prostene bunod than with timolol," she said. 3 Likewise, a 28-day dose ranging comparison study indicated that latanoprostene bunod 0.024% was more efficacious than latano- prost, lowering IOP an additional 1.23 mm Hg, Dr. Serle said. 4 Two studies have confirmed that latano- prostene bunod remained efficacious at the 1-year mark. 3,5 "Tolerability and reported side effects are similar to prostaglandins, with site instil- lation discomfort reported slightly more often with latanoprostene bunod than with latanoprost," Dr. Serle said. "During the clinical trials, tuting therapy early in the disease and protecting these tissues from chronic changes may reduce the long-term severity of glaucoma." Eyeing the agents The first of these drugs to emerge was latanoprostene bunod. "The chemical entity consists of the well- known and commonly used medi- cation latanoprost and a nitric oxide donating moiety called butanediol mononitrate," Dr. Serle said, adding that this compound is broken into the active latanoprost acid and butanediol mononitrate by corneal esterases. The butanediol mononi- trate is then further broken down into the active nitric oxide and an inactive metabolite. Both of these components independently have the ability to increase outflow, Dr. Serle noted. 2 Jason Bacharach, MD, found- ing partner and medical director, Northbay Eye Associates, Sonoma, California, described the latanopro- stene bunod as one drug with two different mechanisms of action. "The latanoprost component im- proves uveoscleral outflow by wid- ening the spacing in the uveal tissue How these new agents are successfully lowering IOP T wo new medications for lowering IOP are gaining traction in the glauco- ma sector, drugs that can increase the outflow of aqueous through the drainage tissue. These unique medications, latano- prostene bunod (Vyzulta, Bausch + Lomb, Bridgewater, New Jersey), which became available in late 2017, and netarsudil (Rhopressa, Aerie Pharmaceuticals, Irvine, Califor- nia), which emerged in early 2018, offer new options for practitioners, according to Janet Serle, MD, pro- fessor of ophthalmology, glaucoma fellowship director, Icahn School of Medicine at Mount Sinai, New York. Here's a closer look at these new outflow drugs. In patients with glaucoma, the trabecular pathway is the site of the diseased tissue, 1 Dr. Serle explained. "The changes in this tissue lead to elevated IOP," she said. "Medica- tions that act directly on this critical tissue to enhance outflow are very important as it is possible that insti- An inside look at outflow drugs for glaucoma continued on page 50 In glaucomatous eyes, new outflow medications help to effectively manage IOP using different mechanisms than traditional agents. Source: Janet Serle, MD

• Blank Page
• Blank Page (1)