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EW FEATURE 38 These seem to give a specific rate of pressure lowering irrespective of what the baseline pressure is, he said. "It's the old adage: Would you rather have a drug that you know 50% of the time lowers the pressure 10 mm of mercury and the other 50% lowers it just 2 or 3, or a drug that always lowers the pressure 5 or 6 mm Hg?" Dr. Simmons said. "I would argue you would rather have the latter." Jason Bacharach, MD, medical director, Northbay Eye Associates, Sonoma County, Calif., and co-di- rector of the glaucoma division, California Pacific Medical Center, San Francisco, explained that the Rho-kinases work differently than the current gold standard prostaglandins. "Rho-kinase works on the trabecular outflow pathway while the prostaglandins primarily work on uveal scleral outflow," Dr. Bacharach said. One of the Rho-kinase inhibitors, AR13324 (Aerie Pharma- ceuticals, Bedminster, N.J.), has an additional mechanism. "It's not just the Rho-kinase inhibition, it also has a norepinephrine transporter," he said. "The Rho-kinase increases trabecular outflow and the norepinephrine transporter decreases aqueous production, so you get a combination effect." At the 2014 American Glaucoma Society meeting, Dr. Bacharach presented results of a trial comparing AR13324 to latanoprost. "It was effective and well tolerated in patients with glaucoma and ocular hypertension," he said of the new Rho-kinase inhibitor. L. Jay Katz, MD, director of the glaucoma service, Wills Eye Hospi- tal, Philadelphia, pointed out that the Rho-kinase inhibitors may be synergistic with latanoprost. "The Rho-kinase inhibitors in particular improve trabecular meshwork outflow, so you would think that with a drug like prostaglandins that would be good because those drugs improve uveal scleral outflow," Dr. Katz said. Dr. Bacharach noted that an- other class of agents being consid- ered is the FPEP3 dual receptor agonists. One being developed by Ono Pharmaceuticals (Osaka, Japan) is under investigation for hyperten- sion or early glaucoma. "It appears to increase both trabecular and uveal scleral outflow," Dr. Bacharach said. "These are early studies, but it suggests that this novel agent is effective at lowering pressure." Dr. Bacharach is an investigator for a medication with a new spin on latanoprost—latanoprostene bunod (Bausch + Lomb, Bridgewater, N.J.), which has a backbone of latanoprost and a nitric oxide-donating side chain. This new formulation is supposed to increase the efficacy of latanoprost, Dr. Bacharach explained. Currently there are 2 separate trials going on involving this agent, one dubbed APOLLO and the other LUNAR. These are designed to compare the efficacy and safety of the test molecule la- tanoprostene bunod administered once daily to timolol 0.5% given twice daily. "The phase 2 studies were complete and latanoprostene bunod met its primary efficacy endpoint and showed positive results on a number of secondary endpoints as well, consistently lowering IOP in a dose-dependent manner," Dr. Bacharach said. When compared to latanoprost, latanoprostene bunod also did better. "All 4 test doses showed greater IOP reduction compared to la- tanoprost, with the difference for 2 of the 4 doses reaching more than 1 mm," he said. "The most common adverse event was ocular hyperemia, which occurred at a similar rate in all treatment groups." There is also a preservative-free latanoprost. "The knock on la- tanoprost has always been that if Glaucoma May 2014 New continued from page 36 "I think there is a tremendous need. We haven't had a new class of medicine in our field for the last 15 to 17 years." –Steven T. Simmons, MD

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