Eyeworld

JUN 2012

EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.

Issue link: https://digital.eyeworld.org/i/78708

Contents of this Issue

Navigation

Page 35 of 79

36 EW CORNEA June 2012 The next wave of novel dry eye therapies Pharmaceutical focus by Maxine Lipner Senior EyeWorld Contributing Editor New agents poised for takeoff L et's face it: Dry eye is every- where, with many patients suffering from this all- too-common condition. EyeWorld looked at some novel therapies working their way through the pipeline that could help bring additional relief to some of these dry eye sufferers. New T-cell modulator Mention T-cell modulator to practi- tioners and Restasis (cyclosporine, Allergan, Irvine, Calif.) immediately comes to mind. Now a new T-cell modulator, SAR 1118 (lifitegrast, SARcode Bioscience, Brisbane, Calif.), is winding its way through channels. Eric D. Donnenfeld, M.D., co-chairman, Cornea, Nassau University Medical Center, East Meadow, N.Y., sees this as an excit- ing new technology. "It works simi- larly in many ways to Restasis," he said. "It's a T-cell modulator but it works more quickly, and in the FDA Phase II trials it worked better than what we saw with Restasis." The new drug helps to tamp down on inflammation. "SAR 1118 is a lymphocyte function-associated antigen inhibitor of the intracellular adhesion molecule I-CAM-1, which prevents binding of T-cell mediated inflammation in dry eye," Dr. Donnenfeld said. He sees the mecha- nism of action here as supporting the concept that inflammation drives dry eye disease. "The binding of LFA-1 to I-CAM-1 is basically the central event that occurs in T-cell activation migration and prolifera- tion," he said. "This new drug re- duces T-cell mediation inflammation by preventing the LFA-1/I-CAM-1 binding, and the Phase II trials were overwhelmingly successful." In Phase II trials, investigators found that there was a rapid improvement in dry eye symptoms. In addition to being well toler- ated, one of the things that makes SAR 1118 promising is how rapidly it appeared to work. "The onset of action is only 2 weeks," Dr. Donnenfeld said. This speed he at- tributes to the novel mechanism of action, which is to act as an LFA-1 levels of omega-3s, and seem to be more efficacious," he said. "I think that we're going to see nutritional supplements play a major role in the management of dry eye and meibo- mian gland dysfunction as well." There are also new polyunsatu- Novel therapies are in development they may help patients with dry eye (pictured here) Source: Alan N. Carlson, M.D. antagonist. "By blocking this inter- action, it acts on active T-lympho- cytes and prevents them from working, while Restasis works on the production of T-lymphocytes," Dr. Donnenfeld said. "So it takes a full cycle of inflammation, which is about 100-110 days, for Restasis to have the full effect." Because there are differences in the mechanism of action, Dr. Donnenfeld sees the potential for SAR 1118 and Restasis to be used in concert. "They are both T-cell lymphocyte inhibitors, and we can postulate that there might be a synergistic effect by using them together, but no one has looked at that," Dr. Donnenfeld said. "We don't know if there's an advantage to using them together or not, but I'm certain that's one thing we'll be looking at." Currently SAR 1118 is in Phase III FDA trials, which should be com- pleted shortly. Dr. Donnenfeld will look to the trials to clarify SAR 1118's potential role in controlling dry eye. "That's going to give us a lot of information on where this drug is best used," he said. Oils in action Also piquing interest are some novel agents that appear to have promise in keeping dry eye symptoms at bay. One product approved for over-the- counter use in the E.U., T-Clair SPHP700-3 (Sinclair Pharma, London), continues to be eyed with interest in the U.S. The agent, which is a combination of linseed extract and polyvinylpyrrolidone, showed promise in a March 2011 study pub- lished in Cornea. In the study, 60 pa- tients with mild to moderate dry eye were given either the preservative- free T-Clair or a placebo. After 2 and 4 weeks of treatment, results showed significant differences between the two groups. No adverse events were reported here. Investigators con- cluded that in mild to moderate dry eye, the agent appeared to be safe and effective in improving tear film stability, ocular surface lubrication, and patient symptoms. Dr. Donnenfeld sees nutritional supplements such as fish oil, rich in omega-3 fatty acids, as being useful here. "Oral nutritional supplements have become very interesting to me in the management of dry eye," he said. While there is some evidence that omega-3 fatty acids have poor absorption and cause gastrointesti- nal side effects, this is not so for newer formulations, finds Dr. Donnenfeld. "Some of the more modern omega-3 fatty acids are the triglyceride forms, which have been processed and have much better ab- sorption, much better purity, and achieve much higher blood stream rated fatty acid agents known as Resolvin analogues (Resolvyx Pharmaceuticals, Cambridge, Mass.) that hold promise when applied topically as drops. Stephen C. Pflugfelder, M.D., professor of oph- thalmology, Cullen Eye Institute, Baylor College of Medicine, Hous- ton, sees these as acting like super fish oil. "The company has claimed that they're about 10,000 times more potent than fish oil in their anti-inflammatory effects," he said. These work on pathways involved in resolving inflammation. Dr. Pflugfelder, who was in- volved in pre-clinical testing with several Resolvin compounds, sees these as having intriguing possibili- ties. "They were found to improve corneal epithelial disease and also to increase the density of goblet cells," he said. "That would indicate that they have promise for treating dry eye syndrome." He pointed out that the company has already performed and completed Phase II clinical trials in humans, which showed efficacy. Plans are under way to move to Phase III clinical trials shortly. These have been found to be very well tol- erated. "They seem to be extremely safe since they're natural molecules that are produced by the body," Dr. Pflugfelder said. "They're synthe- sized from dietary lipids like fish oils into these Resolvin molecules." Overall, he is hopeful that the novel drop will gain clinical trac- tion. "I think that it remains to be seen how [this molecule] will do in Phase III trials," Dr. Pflugfelder said. "If it does get approved I think that it's a great addition to the armamen- tarium." EW Editors' note: Dr. Donnenfeld has financial interests with SARcode Bioscience. Dr. Pflugfelder has financial interests with Allergan and Resolvyx. Contact information Donnenfeld: 516-446-3525, eddoph@aol.com Pflugfelder: 713-798-4732, stevenp@bcm.tmc.edu

Articles in this issue

Links on this page

Archives of this issue

view archives of Eyeworld - JUN 2012