EyeWorld India March 2016 Issue

March 2016 Glaucoma treatment 34 EWAP SECONDARY FEATURE potential labeling, remain unknown at present,” Dr. Realini said. The approval of a Rho kinase inhibitor would bring a new class of agents to glaucoma for the first time in 20 years, said Jacob Brubaker , MD , Sacramento Eye Consultants, Sacramento, Calif. Dr. Brubaker has been part of the Rhopressa clinical trials. Fitting it in the treatment paradigm Just how Rhopressa may be used in the glaucoma paradigm will become clear during the phase 3 studies, said Gary D. Novack, PhD , president, PharmaLogic Development, San Rafael, Calif., and visiting professor of ophthalmology and pharmacology, University of California, Davis, School of Medicine. “I think that it should work throughout the spectrum of disease,” Dr. Brubaker said. “I still think that prostaglandins will likely remain first line, but the studies and clinical experience will reveal its efficacy as well as its tolerability.” As Rhopressa tends to work better with lower baseline IOPs, it could prove to be a better treatment with low-tension glaucoma than what is currently available, Dr. Brubaker said. “At this point, this is speculation, and further study will have to be directed toward these patients in the future.” Another agent under development is a combination drug called Roclatan, also from Aerie, that combines Rhopressa with latanoprost. “In phase 2 trials, it outperformed each of its components—latanoprost and Rhopressa—in IOP reduction,” said Dr. Bacharach, who is a consultant for the company. “If approved, it will be the first fixed-combination drug with a prostaglandin component in the U.S.” “This suggests that Rhopressa may be better positioned as an adjunct to prostaglandin analogues rather than as an alternative first line therapy to prostaglandins,” Dr. Realini said. “We will need more comparative data and some hands- on experience with these drugs before we can best determine their place in the paradigm.” Another fixed-dose combination, Simbrinza (Alcon, Fort Worth, Texas), was approved by the FDA in 2013, Dr. Novack said. The medication combines brimonidine and brinzolamide and treats open-angle glaucoma or ocular hypertension. Still other agents that target the trabecular meshwork are making their way through clinical testing, Dr. Brubaker said. These include trabodenoson (Inotek, Lexington, Mass.), which is a selective adenosine mimetic that works at the A1 receptor subtype in the trabecular meshwork. Phase 2 trial results show that the drug may lower IOP to a similar level as prostaglandins, and phase 3 trials should begin by the end of this year, Dr. Brubaker said. Seeking more glaucoma treatment innovation Financial hurdles may have been the reason for some stagnation in glaucoma treatment innovation, Dr. Novack thinks. “Drug development is primarily sponsored by the private sector and is dependent on perceived return on investment,” he said. He still thinks there is financial opportunity for the development of new glaucoma medications, even if they are not first-line therapy. He also thinks that new drug delivery systems could be a win–win for both glaucoma specialists and patients. “Innovation for finding new therapeutic targets and developing novel drugs with unique mechanisms of action is more expensive, time-consuming, and risky,” Dr. Realini said. He speculated that limiting the development of the number of similar drugs in a given class could possibly spur innovation, so drug makers would not focus on therapies that are nearly identical to what is already in the marketplace. That said, right now is actually a good point in time for glaucoma drug innovation, Dr. Brubaker said. “There is more interest in novel agents than there has been for quite some time since prostaglandins came on the scene,” he said. “Since then, the majority of research has been directed toward improving existing products, creating preservative- free versions, or developing combination products.” The Rho kinase inhibitors on the horizon indicate an interest in glaucoma drug innovations, as does Vesneo (latanoprostene bunod, Bausch + Lomb, Bridgewater, NJ, and Nicox, Sophia Antipolis, France), a nitric oxide-donating prostaglandin currently under FDA review, he said. Dr. Bacharach thinks the FDA may play a more collaborative role going forward with the development of glaucoma therapies. “Although drug development in glaucoma has been limited for the past two decades, I am optimistic for the future. The FDA has made it clear that they want to partner with the R&D establishment to streamline drug and device pathways for innovator companies to follow,” he said. EWAP Reference 1. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treat- ment Study: a randomized trial deter- mines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol . 2002;120:701–13. Editors’ note: Drs. Bacharach has financial interests with Aerie Pharmaceuticals. Drs. Brubaker, Novack, and Realini have no financial interests related to this article. Contact information Bacharach: jb@northbayeye.com Brubaker: jbrubaker@saceye.com Novack: gary_novack@pharmalogic.com Realini: hypotony@gmail.com Finding new therapies - from page 32